5
Heritable Disorders of Connective Tissue and Effects on Function
As discussed in previous chapters, heritable disorders of connective tissue (HDCTs) manifest as physical and mental secondary impairments, potentially in many different body systems. The severity of the disease process varies among individuals and relates to the type, number, and severity of the secondary impairments, as well as the combined effects of multiple “less severe” impairments.
As described in Chapter 1, the International Classification of Functioning, Disability and Health (ICF) model of disability identifies three domains of functioning: (1) body function and structure (i.e., physiological functions of the body, including psychological functions, and functioning of body structures); (2) activities (i.e., actions or tasks); and (3) participation (i.e., performance of tasks in a societal context, such as school or work (WHO, 2001). “Impairments” are deficits in body function and structure; “limitations” refer to deficits in completing activities; and “restrictions” refer to reductions in participation (WHO, 2001). Personal and environmental factors act on the ICF domains to either enhance or diminish an individual’s activity and participation.
Some effects of HDCTs, and in some cases their treatment, manifest as impairments in body structures and physical and psychological functions, with resulting activity limitations and restrictions on participation. The impairments associated with HDCTs affect mental (e.g., cognitive, psychosocial, emotional) functioning as well as physical functioning.
Moreover, these areas of functioning interact such that impairments in one area (e.g., physical) may precipitate or exacerbate impairments in one or more of the others (cognitive, psychosocial, and/or emotional). Chronic pain, for example, is reported to have a bidirectional relationship with depression (Vadivelu et al., 2017), and an association between gastrointestinal and psychological disorders has also been reported (Stasi et al., 2017). Similarly, physical conditions such as pain and fatigue can adversely affect cognitive functioning (Higgins et al., 2018; Moriarty et al., 2011; Vadivelu et al., 2017).
This chapter first describes the relationship between secondary impairments associated with HDCTs and functioning, and then provides an overview of the potential effects on global (full-body); physical; vision, hearing, and speech; and mental functioning. The chapter also reviews selected listings from the U.S. Social Security Administration’s (SSA’s) Listing of Impairments that may be particularly applicable to individuals with specific HDCTs.
SECONDARY IMPAIRMENTS
The statement of task for this study asks the committee “to describe to the degree possible” the “secondary impairments that result from either the [selected HDCTs] or their treatments (if applicable).” As defined in Chapter 1, the committee understands “secondary impairments” to mean physical and mental manifestations (medical diagnoses, syndromes, or health conditions) that are associated with and may also result from an HDCT, although they may occur independently in individuals without an HDCT. Annex Tables 5-3–5-12 at the end of this chapter present selected manifestations (organized by body system) and some of the HDCTs with which they are associated, as well as common diagnostic techniques and potential treatments.
The number, type, and severity of the secondary impairments experienced by an individual with an HDCT drive the person’s functioning and potential disability. Annex Tables 5-13–5-16 summarize the potential implications of secondary impairments for global functioning; physical functioning; vision, hearing, and speech functioning; and mental functioning in individuals with HDCTs. The tables list physical and mental activities the
committee determined to be of particular interest to SSA,1 the potential reasons for limitations in those activities for individuals with HDCTs, selected measures for assessing function in the relevant areas, and selected assistive technologies and reasonable accommodations that could help mitigate the effects of the impairment(s) on an individual’s ability to work, participate in school, and the like. The assessment measures are categorized primarily as performance-based or self-reported. Performance-based measures require that the individual being assessed perform a set of physical or mental activities or tasks so that his or her ability to execute them can be ascertained. Self-reported (or proxy-reported) measures require the individual being assessed or a third party to complete a questionnaire asking about symptoms (e.g., pain, fatigue, anxiety) or the individual’s ability to perform a specific set of mental or physical tasks. Patient-reported outcome or experience measures, questionnaires regarding activities of daily living (ADLs) and instrumental activities of daily living (IADLs), and some types of psychological tests are examples of such measures.
The medical tables (Annex Tables 5-3–5-12) and the function tables (Annex Tables 5-13–5-16) in this chapter can be used together to understand how secondary impairments associated with different HDCTs may affect an individual’s functioning in various areas. The “potential reasons” column in the function tables provides information and cross-references that allow the reader to identify the relevant medical tables (e.g., musculoskeletal, neurological), which include information about specific diagnoses.
As discussed in the final section of the chapter, the secondary impairments identified in the medical tables can also serve as an interface with
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1 SSA classifies jobs as sedentary, light, medium, heavy, and very heavy based on the level of physical exertion requirements of the work (CFR § 416.967). Annex Table 5-1 provides the definitions for each level of work. When a person applies for disability benefits, SSA collects information about the applicant’s physical and mental impairment(s) and functioning from a variety of sources, including the applicant, medical providers, employers, teachers, and other third parties with knowledge of the applicant. Information collected about physical functioning includes information about such activities as sitting, standing, walking, lifting, carrying, reaching, handling large objects, writing, typing, handling small objects, and low work (stooping, kneeling, crouching, crawling) (SSA, 2020). Information is collected as well about the applicant’s ability to perform various daily activities, such as dressing, bathing, self-feeding, and using the toilet, as well as preparing meals, doing house- and yardwork, getting around, shopping, and the like. SSA also must consider information about the physical and mental demands of different jobs, such as the amount of time an employee is required to stand or walk and whether a job requires driving, using a keyboard, or reaching overhead (SSA, n.d.-a). The physical; vision, hearing, and speech; and mental activities addressed in this chapter (Annex Table 5-2) are those the committee determined to be most relevant to SSA based on the information SSA collects about applicants and the information the U.S. Bureau of Labor Statistics collects about the physical and mental demands of jobs for inclusion in the Occupational Information System, which is being developed to serve as the main source of occupational information for SSA’s disability adjudication process (SSA, 2022).
existing SSA listings. For example, some individuals with HDCTs applying for SSA disability benefits might qualify at the listing level step in the determination process on the basis of the secondary impairment(s) they are experiencing rather than the HDCT itself.
ENVIRONMENTAL FACTORS AND FUNCTIONING
Environmental factors can adversely affect functioning in some people. Environmental factors that can impair an individual’s functioning include extreme heat and cold; noise; vibration; wetness; humidity; and atmospheric conditions that can affect the respiratory system, nervous system, eyes, or skin (e.g., scents, allergens, fumes, noxious odors, dusts, mists, gases, and poor ventilation) (BLS, 2020). SSA recognizes this and takes an individual’s environmental restrictions into account. “A nonexertional impairment is one which is medically determinable and causes a nonexertional limitation of function or an environmental restriction” (SSR 85-15, emphasis added; SSA, n.d.-f). Accordingly, SSA takes into account the relative availability of jobs that would not expose an affected individual to the relevant environmental factors. For example, a restriction on exposure to excessive amounts of noise, vibration, or dust would have little effect “because most job environments do not involve great noise, [vibration, or] amounts of dust” (SSA, n.d.-f). But “where an individual can tolerate very little noise, [vibration, or] dust, …the impact on the ability to work would be considerable because very few job environments are entirely free of [such] irritants…” (SSA, n.d.-f).
Environmental factors can significantly affect functioning in some individuals with HDCTs. For example, patients with the Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD) are at increased risk of mast cell activation disease (MCAD), a condition that can be triggered by environmental substances (Frieri, 2018). Humidity and changes in atmospheric pressure appear to have a negative effect on functioning in EDS/HSD patients, which causes psychosocial distress (Palomo-Toucedo et al., 2020). There may be a number of reasons for this effect on functioning. First, patients with EDS/HSD have lowered cold and heat pain thresholds (Di Stefano et al., 2016). In addition, migraine, known to be more common in patients with either Marfan syndrome (MFS) (von Kodolitsch et al., 2019) or EDS/HSD (Puledda et al., 2015) relative to the general population, are triggered by environmental substances and weather changes (Marmura, 2018). Furthermore, cardiovascular autonomic dysfunction in EDS/HSD patients appears to have environmental triggers (Hakim et al., 2017b), and changes in temperature and barometric pressure can exacerbate joint problems and symptoms of dysautonomia and affect intracranial pressure (Herbowski, 2017, 2019; Palomo-Toucedo et al., 2020). Likewise, sound,
odors, light, and foods can trigger or exacerbate manifestations in individuals with EDS/HSD (Syx et al., 2017).
GLOBAL FUNCTIONING
Chronic pain, chronic fatigue, and a type of cognitive dysfunction or mild cognitive impairment sometimes referred to as “brain fog” are some of the most common and potentially disabling manifestations of EDS/HSD, especially hypermobile EDS (hEDS)/HSD (Arnold et al., 2015; Chopra et al., 2017; Ocon, 2013; Raj et al., 2018; Rombaut et al., 2011; Ross et al., 2013; Sacheti et al., 1997; Voermans et al., 2010a; Wells et al., 2020). Chronic pain and fatigue are also common among individuals with MFS (Nelson et al., 2015b; Peters et al., 2001; Ratiu et al., 2018).
This section begins with a discussion of the effect of chronic pain and chronic fatigue on global functioning and selected measures for assessing their severity. It then reviews the roles of two global modulators of function (orthostatic intolerance and MCAD) in individuals with EDS/HSD, particularly hEDS/HSD. The section concludes with a discussion of two categories of measures for assessment of global functioning.
Chronic Pain
Pain can be characterized in two broad ways. The first is by its cause. Neuropathic pain is caused by damage to or irritation of the nerves themselves. Nociceptive pain is caused by stimulation of pain receptors, which send signals to the brain leading to the experience of pain. Depending on the location of the pain receptors, nociceptive pain may be somatic (surface of the body or musculoskeletal system) or visceral (stemming from pain receptors within the body cavity). Nociplastic pain arises from altered nociception in the absence of damage to the somatosensory system or stimulation of pain receptors in response to an assault (IASP, 2021). Most EDS/HSD patients experience all three types of pain.
Pain also may be classified by its duration. Typically, acute pain is a time-limited response to an injury (e.g., pulled muscle, broken bone) or warning of potential injury (e.g., from a hot stove or sharp object). Chronic pain has been defined as “persistent or recurrent pain lasting longer than 3 months” (Treede et al., 2015; WHO, 2021). Breakthrough pain occurs when an episode of acute pain “breaks through” otherwise well-controlled chronic pain.
Everyone experiences acute pain from time to time. While estimates indicate that 20 percent of individuals worldwide experience chronic pain (Treede et al., 2015), studies have found that 80–100 percent of individuals with EDS, especially hEDS/HSD, and MFS experience chronic pain (Chopra
et al., 2017; Nelson et al., 2015a; Peters et al., 2001; Ratiu et al., 2018; Rombaut et al., 2011; Speed et al., 2017; Voermans et al., 2010a).
The International Classification of Diseases, Eleventh Edition (ICD-11) (WHO, 2021) identifies seven categories of chronic pain, five of which are most relevant to individuals with HDCTs such as EDS/HSD and MFS: (1) chronic primary pain, (2) chronic secondary musculoskeletal pain (Voermans et al., 2010a), (3) chronic secondary visceral pain (Fikree et al., 2017), (4) chronic neuropathic pain (Camerota et al., 2011; Rombaut et al., 2015), and (5) chronic secondary headache or orofacial pain (Mitakides and Tinkle, 2017). Individuals with EDS/HSD may also appear to be more predisposed to chronic postsurgical or posttraumatic pain (Chopra et al., 2017; Voermans et al., 2010a), perhaps because of increased difficulty with healing. The seventh pain category, chronic cancer-related pain, does not apply to pain secondary to an HDCT.
Potential Reasons
Individuals with hEDS/HSD may experience neuropathic or nociceptive pain (Camerota et al., 2011; Rombaut et al., 2015; Voermans et al., 2010a), and some individuals also experience central sensitization, stemming from “a generalized hyperexcitability of central nociceptive pathways” (Rombaut et al., 2015, p. 1126). Pain is most frequently reported in the neck, shoulders, hips, and legs (Voermans et al., 2010a).
Chronic pain and hypersensitivity are explained by peripheral and central sensitization. Persistent nociceptive input from musculoskeletal and visceral sources can lead to peripheral and central sensitization, which often perpetuates chronic pain through processes involving neuroplasticity (Ji et al., 2018; Matsuda et al., 2019). In response to persistent nociceptive signaling from peripheral sensitized tissue, a number of synapse-to-nucleus messengers are recruited. As peripheral sensitization persists, it leads to central sensitization. Peripheral sensitization is accompanied by a reduction in threshold and increase in magnitude of response at the peripheral end of sensory nerve fibers (Gangadharan and Kuner, 2013). Chemical inflammatory mediators (e.g., mast cells, platelets, neutrophils, basophils, endothelial cells) are released by nociceptors and non-neuronal tissue. This release of inflammatory mediators can exacerbate local connective tissue dysfunction and local tissue damage (Chiu et al., 2012). Furthermore, since histamine is a key mediator in neurogenic inflammation (Rosa and Fantozzi, 2013), the prevalent comorbidity of MCAD with HCDTs suggests that neurogenic inflammation may contribute to the link between peripheral or central sensitization and connective tissue involvement in HDCTs.
Under normal circumstances, the spinal cord sends modulatory signals to suppress pain signals. When a constant barrage of pain signals reaches
the spinal cord, it causes sensitization of the dorsal horn cells; as a result, the central nervous system (CNS) switches from suppressing signals to enhancing its response to stimuli. The persistent barrage of pain signals to and increased modulatory signals from the CNS lead to central sensitization. Central sensitization explains why chronic pain persists and even increases.
Pain may be caused by secondary impairments in virtually every body system, including musculoskeletal disorders, such as joint subluxations or dislocations and myofascial disorders (see Annex Table 5-3); neurological disorders, such as neuropathies, and nerve compression disorders (see Annex Tables 5-3 and 5-4); gastrointestinal disorders, such as gastroenteritis, mast cell disorders, and inflammatory bowel disease (see Annex Table 5-8); and genitourinary disorders, such as chronic pelvic pain and dysmenorrhea (see Annex Table 5-10). MCAD (see Annex Table 5-7) contributes to pain through the role of mast cells in neurogenic inflammation, which causes pain as well as itching (Gupta and Harvima, 2018), and in immune-mediated disorders that cause pain (see, e.g., Annex Tables 5-4 and 5-8). In addition, individuals with chronic pain have a higher risk of developing symptoms of anxiety or depression, and individuals with anxiety or depression are more likely to experience chronic or intensified pain (Anxiety & Depression Association of America, 2021; Harvard Health Publishing, 2017; Vadivelu et al., 2017). Poor sleep quality, experienced by many individuals with EDS/HSD, also contributes to the experience of pain (Voermans et al., 2010a).
Interventions
Management of chronic pain depends on the type of pain (nociceptive, neuropathic, or nociplastic) and its location. Notably, individuals with HDCTs may experience multiple root causes of pain and related loss of function, necessitating a comprehensive approach to their evaluation and treatment. Treatment often is multimodal, involving physical therapy, occupational therapy, medication, psychological interventions, surgical co-management, good sleep hygiene, education, and taking care of one’s overall health. Although analgesics and other treatments (e.g., braces) may be used to mitigate pain and improve functionality, it is important to identify and address the root cause(s) of the pain and, when applicable, implement preventive measures to reduce the risk of recurrence (Chopra, 2020). For example, pain caused by a dislocation would be treated by fixing the dislocation (underlying cause), potentially treating the acute pain with analgesics until it had resolved, and prescribing physical therapy and exercises to reduce the risk of another dislocation. Although anti-inflammatory and nerve pain medications may be used to treat pain, opioids typically are not helpful for individuals with EDS/HSD and may exacerbate other symptoms,
such as those associated with certain gastrointestinal disorders and MCAD (Chopra, 2020). Use or overuse of steroids can lead to increased instability in joints, as well as increased risk for glaucoma and cataracts (Liu et al., 2103).
Selected Assessment Measures
Because the experience of pain differs from individual to individual, the gold standard of pain assessment is self-report. Annex Table 5-13 (on global functioning) includes a list of several common self-reported pain measures.
Effects on Functioning
Chronic pain in particular can adversely affect individuals’ functioning. Voermans and colleagues (2010a) found that pain severity among individuals with EDS/HSD was independently related to functional impairment. Children with chronic pain may experience significant adverse effects on participation in academic, athletic, and social activities (Rabin et al., 2017).
Pain can interfere with all types of physical activities that may be involved in work or school, including such sedentary activities as sitting at a desk, writing, or working on a computer. Chronic pain also has an effect on cognitive functioning, including such areas as long-term memory, selective attention, processing speed, and executive functioning (Berryman et al., 2013, 2014; Khera and Rangasamy, 2021; Lee et al., 2010; Ratiu et al., 2018).
Chronic Fatigue
Chronic fatigue has been defined as persistent or recurrent tiredness or exhaustion that typically persists for 6 months or more, cannot be explained by other diagnoses, does not result from ongoing exertion, is not alleviated by rest or sleep, and prevents patients from carrying out normal activities (Hakim et al., 2017a). EDS/HSD has long been associated with a high prevalence of chronic fatigue, which, together with pain, is an important determinant of impaired health-related quality of life in this condition (Ritelli et al., 2020; Rombaut et al., 2010). It has been estimated that more than 75 percent of patients with EDS/HSD suffer from severe fatigue, which appears to be more common in hEDS/HSD than in the classic type of EDS (Ritelli et al., 2020; Voermans et al., 2010b). Fatigue in patients with hEDS/HSD is different from tiredness and has several symptoms that overlap with a condition called myalgic encephalomyelitis (ME), or chronic fatigue syndrome (CFS) (ME/CFS) (Hakim et al., 2017a). Chronic fatigue may be a major presenting symptom of hEDS/HSD, and an appropriate diagnostic
workup should distinguish between hEDS/HSD and ME/CFS (Hakim et al., 2017a). Fatigue also has been reported in as many as 89 percent of individuals with MFS (Bathen et al., 2014; Peters et al., 2001; van Dijk et al., 2008).
Potential Reasons
Common causes of fatigue in patients with EDS/HSD include the following:
- Ligament laxity. People with EDS/HSD have ligament laxity, or loose ligaments, which can require muscles, including those in the proprioceptive system responsible for balance, to work harder to compensate for the laxity and joint instability. People with ligament laxity resulting from EDS/HSD may experience postural instability and rely on muscles to maintain postural control (Galli et al., 2011). However, these muscles are affected by weak connective tissue, resulting in extra work for them to maintain posture, and this excess demand on muscles can cause fatigue.
- Dysautonomia. Many people with EDS/HSD experience orthostatic intolerance (described later in this chapter), or dysautonomia (dysfunction of the autonomic nervous system that controls involuntary bodily functions). Patients with secondary dysautonomia—that is, dysautonomia associated with a disease such as EDS/HSD—may experience a variety of symptoms including fatigue, balance problems, mild cognitive impairment, weakness, and exercise intolerance (De Wandele et al., 2016). Postural orthostatic tachycardia syndrome (POTS; discussed in the section on orthostatic intolerance) is one form of dysautonomia, as is pure autonomic failure, which is characterized by tiredness, dizziness, and fainting (Cleveland Clinic, 2020).
- Medication. Some medications, such as benzodiazepines and antidepressants, have sedative side effects that can contribute to fatigue (Voermans et al., 2010b). People with EDS/HSD are often prescribed multiple medications for pain, MCAD, POTS, or other forms of dysautonomia, and some or all of these medications can contribute to lethargy, which adds to fatigue.
- Nonrestorative sleep. People with EDS/HSD and dysautonomia experience either decreased parasympathetic tone or an excessively high sympathetic activity that essentially keeps one’s brain active when sleeping. These patients often present with nonrestorative sleep that may be the result of pain, nocturnal tachycardia, or
- sleep-disordered breathing (sleep apnea) (Hakim et al., 2017a; Ritelli et al., 2020).
- Nutritional. Gastrointestinal issues, including bowel dysfunction, are common in EDS/HSD (Fikree et al., 2017; Ritelli et al., 2020). They vary from slowing of intestinal motility to chronic nausea, constipation, and/or diarrhea. Malabsorption and poor nutritional status can result in nutritional deficiencies, including low iron storage levels that may result in decreased blood oxygen levels with concomitant fatigue.
- Physical deconditioning. Chronic pain, poor physical activity, and exercise intolerance can result in fatigue upon exertion (Hakim et al., 2017a; Ritelli et al., 2020).
Other manifestations of EDS/HSD associated with chronic fatigue include chronic pain, anxiety and depression, nocturnal micturition (possibly contributing to nonrestorative sleep), and headaches and migraines (Hakim et al., 2017a; Ritelli et al., 2020).
Interventions
Treatment of the fatigue associated with EDS/HSD is multimodal and may require a team of health care experts. Medications, such as antidepressants, pain medications, anti-anxiety drugs, sleep aids, and medications for orthostatic intolerance, may be used to address the underlying causes of the fatigue. Nutritional supplements and dietary modification, preferably based on recommendations from a dietician, may help with nutritional deficiencies. Lifestyle modifications, such as rest and relaxation techniques and good sleep hygiene, can also help alleviate some aspects of fatigue. Graded exercise therapy may be appropriate for some patients with joint hypermobility. Relaxation techniques (e.g., yoga, mindfulness, progressive muscle relaxation), other exercise regimens, physical therapy, and planned management of daily activities are also important therapeutic approaches to fatigue, but all of them must be tailored to the individual patient’s needs. Finally, cognitive-behavioral therapy may be beneficial for encouraging exercise and adherence to the lifestyle modifications necessary to control the underlying causes of the fatigue, including anxiety, depression, and chronic pain (Hakim et al., 2017a). In some more severe cases, assistive devices, such as wheelchairs and reachers, may be necessary.
One important aspect of chronic fatigue associated with HDCTs is that it is often unpredictable. Patients report that they may be functioning well one day and completely unable to perform job-related activities and ADLs the next. This variability in performance capability may lead to frequent absences from work and difficulty in maintaining employment.
Selected Assessment Measures
Assessment of chronic fatigue is based on self-reports, and a number of self-report instruments are available to provide a consistent measure of the impact and severity of fatigue. These instruments include the Brief Fatigue Inventory, the Fatigue Impact Scale, the Fatigue Severity Scale, the Fatigue Symptom Inventory, the Multidimensional Assessment of Fatigue scale, and the Multidimensional Fatigue Symptom Inventory. It must be noted, however, that these instruments are used most often in research and are not typically used in the clinical setting. The Wood Mental Fatigue Inventory is one instrument that can be used in the clinic to assess the cognitive symptoms of fatigue (Hakim et al., 2017a). The CRESTA Fatigue Clinic booklet (Newcastle upon Tyne Hospitals: NHS Foundation Trust, 2020), developed by the UK National Health Service Foundation Trust, uses a patient-oriented approach to help patients identify what daily tasks and activities result in fatigue and how often, and encourages them to keep an activity log. Such self-report measures may assist both the patient and clinician in developing an exercise program and a symptom management plan to minimize fatigue on an ongoing basis.
Effects on Functioning
Chronic fatigue associated with HDCTs can result in a number of functional impairments that affect daily activities; the more severe the fatigue, the greater is the impairment (Voermans et al., 2010b). These impairments can include an inability to remain upright for even short periods of time, difficulty with concentration (De Wandele et al., 2016), difficulty in moving from standing to sitting and back to standing, and decreased executive functioning resulting from poor sleep; planning and sequencing, memory, and attention may also be affected (Capuron et al., 2006; Dobbs et al., 2001; Joyce et al., 1996; Ratiu et al., 2018). Many patients with EDS/HSD rest or sleep during the day as a result of their fatigue, which can impact social functioning, work, and other activities (Voermans et al., 2010b). The inability to remain upright or standing in particular can negatively affect the performance of many normal activities for both children and adults. In one study, parents of children aged 4–12 years reported that their children were unable to “keep up with peers” because of fatigue and other factors (Warnink-Kavelaars et al., 2019). Fatigue also can prevent people with EDS/HSD from working at jobs that are physically demanding (De Baets et al., 2021). One study found that fatigue was the major reason people with hEDS did not work (De Baets et al., 2021). And a Norwegian study of individuals with MFS found severe fatigue to be “significantly associated with low work participation” (Velvin et al., 2015; see also Bathen et al., 2014).
Orthostatic Intolerance2
Orthostatic intolerance refers to a condition in which individuals develop symptoms upon assuming and maintaining upright posture, with symptoms improving (although not necessarily resolving completely) after they return to a recumbent position (Low et al., 2009). Symptoms, many of which overlap with those of EDS/HSD, include rapid heart rate (tachycardia) or palpitations, feeling faint or fainting, lightheadedness or dizziness upon standing, vertigo, blurred vision, weakness, fatigue, pain, headaches, anxiety, exercise intolerance, difficulty regulating body temperature, sensitivity to auditory or visual stimuli, nutrient imbalance, and cognitive difficulties (Goodman, 2018; Rich et al., 2020).
Hemodynamic abnormalities in orthostatic intolerance can include classical or delayed orthostatic hypotension, neurally mediated hypotension, and POTS (Freeman et al., 2011; Goldstein et al., 2002; Low et al., 2009; Rosen and Cryer, 1982; Schondorf and Low, 1993; Sheldon et al., 2015; Stewart et al., 2018). Classical orthostatic hypotension, common in particular in older adults, is defined by a sustained blood pressure reduction of at least 20 mm Hg systolic or 10 mm Hg diastolic during the first 3 min after assuming an upright posture (Freeman et al., 2011). POTS is increasingly being recognized as a common form of orthostatic intolerance in individuals with EDS/HSD, and is diagnosed (1) in the absence of orthostatic hypotension in the first 3 minutes of standing or tilt testing, and (2) upon an increase in heart rate of ≥ 30 beats per minute (bpm) in adults (≥ 40 bpm in those under age 20 years) in the first 10 minutes after going from recumbent to standing or passive upright tilt; a heart rate of > 120 bpm during the first 10 minutes upright may be an additional criterion (Roma et al., 2018; Rowe, 2022). Inappropriate sinus tachycardia, which has symptoms similar to those of POTS, is characterized by a sinus rhythm with a heart rate greater than 100 bpm at rest (Sheldon et al., 2015). Neurally mediated hypotension, which occurs in both adults and children, is a reflex form of hypotension, and is defined by at least a 25 mm Hg reduction in systolic blood pressure, often accompanied by a relative slowing of the heart rate at the time of presyncope or hypotension (Rowe, 2022).
The true prevalence of orthostatic intolerance in EDS/HSD is not known. In clinical studies, however, 41–100 percent of people with joint hypermobility or EDS have reported orthostatic symptoms on a regular basis (Rowe, 2022).
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2 This section draws heavily on a paper by Peter Rowe (2022) commissioned by the committee (see Appendix B).
Potential Reasons
Orthostatic intolerance results primarily from two physiological changes in response to upright posture: (1) a reduction in cerebral blood flow, and (2) an exaggerated compensatory adrenergic response to the reduction in cerebral blood flow (Low et al., 2009). Other potential causes of orthostatic intolerance in persons with HDCTs include the development of autoantibodies to adrenergic receptors and rarely Chiari I malformation (Hakim et al., 2017b). The reduction in cerebral blood flow may result from excessive gravitational pooling of blood, low blood volume, and an increased sympathetic nervous system and adrenal catecholamine response (Rowe, 2022). Increased peripheral pooling of blood or decreased vasoconstriction is affected by the duration of quiet upright posture, increased compliance of the blood vessel wall in response to hydrostatic pressure, the presence of venous varicosities, obstruction of venous return, and vasodilating substances. Low blood volume occurs with a variety of conditions of orthostatic intolerance, including POTS and ME/CFS (Hurwitz et al., 2009; Okamoto et al., 2012; Streeten and Bell, 1998). Low blood volume has been associated with lower renin:aldosterone ratios and lower levels of antidiuretic hormone (Okamoto et al., 2012; Wyller et al., 2010). Physical inactivity can result in reductions in plasma volume, thereby aggravating symptoms of orthostatic intolerance and interfering with daily function (Rowe, 2022).
Interventions
Management of orthostatic intolerance requires a comprehensive care program beginning with nonpharmacologic interventions. These interventions include (1) avoiding conditions that increase dependent pooling of blood, such as prolonged standing or sitting; (2) improving venous return to the heart by using the muscle pump of the lower limbs, such as by crossing the legs while standing or shifting weight from one leg to the other and using compression garments; (3) avoiding depletion of salt and water and other causes of low blood volume; and (4) avoiding increasing catecholamines beyond their baseline levels (which may be elevated) by minimizing stress and in some patients reducing caffeine consumption (Rowe et al., 2017). Further care focuses on managing migraine headaches; allergies; mast cell activation syndrome; anxiety; depression; menstrual dysfunction; and areas of biomechanical dysfunction, which can be managed with physical therapy or osteopathic manual therapy, as well as occupational therapy and environmental modifications (Levine et al., 2021; Rowe, 2016). Individuals with POTS and fatigue may need to lie down during the day to avoid flares of their condition.
Most individuals with more than a minor degree of functional impairment from orthostatic intolerance will need medication. Pharmacologic treatments, such as low-dose beta blockers, fludrocortisone, or midodrine, may ameliorate some of the effects of the condition. Those with neutrally mediated hypotension (NMH) may benefit from selective serotonin reuptake inhibitors. Adolescent girls and women may benefit from hormone therapy (Rowe, 2022, citing Boehm et al., 1997). And individuals with POTS with fatigue and tachycardia may be treated with ivabradine (Rowe, 2022).
Assessment
Clinical assessment of orthostatic intolerance is based on two main tests—standing tests and head-up tilt tests. There is no gold standard for such assessments, and techniques for these tests vary (Rowe, 2022). The impact of orthostatic intolerance on overall function is best assessed with self-reported health-related quality of life questionnaires, such as the SF-36, Euro QOL, or PROMIS measures in adults (Cook et al., 2012; EuroQol Group, 1990; Ware and Sherbourne, 1992) and the age-specific Functional Disability Inventory of Pediatric Quality of Life (PedsQL) for children (Varni et al., 2001). Brief self-reported measures of general or cognitive fatigue include the PedsQL Mutidimensional Fatigue Inventory (MFI), the Wood Mental Fatigue Inventory, and the Fatigue Severity Scale, among others. The SF-36 physical functioning scale can distinguish between diseased and nondiseased individuals. However, it is less useful for ascertaining the degree of disability in individual patients (van Campen et al., 2020). This may be the case for those with EDS/HSD, as function can be affected not just by orthostatic intolerance and fatigue but also by joint stability and pain.
Effects on Functioning
The symptoms of orthostatic intolerance and ME/CFS and their severity can be unpredictable. They are influenced by the level of activity or degree of orthostatic and other physiologic stressors in the preceding days, which can provoke postexertional malaise (PEM). PEM denotes an exacerbation of any of a variety of symptoms—fatigue, lightheadedness, cognitive dysfunction, headache, sensitivity to sensory stimuli, and generalized pain—after people have increased their usually tolerated physical, cognitive, or orthostatic stress (Rowe, 2022).
In a study by Ross and colleagues (2013), 96 percent of patients with POTS self-reported cognitive deficits, referred to as “brain fog.” Blurred or double vision can impact reading, driving, and mobility, and acute
sensitivity to smells, temperatures, sounds, and lights can affect socialization, child care, bathing, and participation in such activities as grocery shopping and doctor’s appointments (Rich et al., 2020). A consistent finding among people with orthostatic intolerance is exacerbation of symptoms in the morning (Rich et al., 2020).
Mast Cell Activation Disease
Mast cells reside throughout the connective tissues, but tend to cluster in the skin and at the epithelial borders of the gastrointestinal, respiratory, and urogenital tracts, which interact with the external world. Mast cells have a variety of functions, including phagocytosis, antigen presentation, cytokine and chemokine production, and the release of vasoactive substances; they also play a role in local tissue homeostasis (tissue repair, angiogenesis) and coordination of immune responses to numerous pathogens (Seneviratne et al., 2017). MCAD is an immune syndrome that can be localized; localized mast cell disorders include, for example, rhinitis, hypersensitivity gastroenteritis, asthma, and urticaria. Systemic mast cell activation, called mast cell activation syndrome, presents with symptoms involving two or more organ systems (skin: urticaria [hives], angioedema [swelling under the skin], and flushing; gastrointestinal: nausea, vomiting, diarrhea, and abdominal cramping; cardiovascular: hypotensive syncope [fainting] or near syncope and tachycardia; respiratory: wheezing; naso-ocular: conjunctival injection, pruritus [itching], and nasal congestion) (Akin, 2017).
Mast cell activation syndrome can result from abnormal production of progenitor mast cells with genetic mutations or mast cell activation events triggered by comorbid disorders (Akin, 2017). The former etiology reflects clonal mast cell disorders with a neoplastic gain of function leading to production of abnormal mast cells; an example of this type of disorder is systemic mastocytosis. The latter etiology reflects mast cell activation that is disproportionate to that required to protect the body from the perceived assault (Akin, 2017). This second form of mast cell activation syndrome, termed nonclonal or secondary mast cell activation syndrome, is the more prevalent and reflects inappropriate activation of the cells to stimuli that otherwise would be tolerated if the individual were in a nonreactive state (Akin, 2017; Hamilton, 2018).
Mast cell dysregulation appears to play a role in EDS/HSD, as well as neuropathies and hypersensitivity syndromes, both immediate and delayed (Seneviratne et al., 2017). Co-occurrence of MCAD and EDS, particularly hEDS/HSD, has been linked to primary immunodeficiency disorders in these patients (Brock et al., 2021). In a study of 974 patients attending an allergy/immunology clinic, Brock and colleagues (2021) sought to identify those with the diagnostic codes for immunoglobulin deficiency, MCAD, and
hEDS/HSD. They found that 46 percent of the 974 patients had MCAD but no codes for immunoglobulin deficiency or hEDS/HSD, 10 percent had a diagnosis of both MCAD and hEDS/HSD, and 19 percent had a diagnosis of all three disorders. The authors point out that HDCTs may increase susceptibility to aberrant mast cell activation (Brock et al., 2021).
Potential Reasons
Mast cells are closely associated with the epithelium of internal organs and the endothelium lining blood vessels and the lymphatic system and play a central role in the detection of and response to tissue injury. As described by Brock and colleagues (2021), mast cells are activated by factors derived from injured connective tissue, as well as activated inflammatory cascades. Following detection of danger or inflammatory signals, mast cells use an array of pathogen receptors to determine the nature of the impending danger, which may include infectious agents, toxins, and physical insults. Mast cells are thereby primed to release their cache of chemical mediators to recruit and activate other components of the innate and adaptive immune systems, as well as release chemicals that play a role in regulating angiogenesis, tissue remodeling, and wound healing (Brock et al., 2021).
Interventions
Treatment for MCAD is typically based on the etiology of mast cell reactivity, clonal versus nonclonal MCAD, triggers of mast cell activation events, and symptoms (see Annex Table 5-7). Therapy starts with identification and avoidance of triggers, such as foods, physical environmental factors, and medications. The latter category of triggers is important in the setting of pain management and surgeries, since several antibiotics, anesthetic agents, and pain relievers, including opioids and nonsteroidal anti-inflammatory agents, are known to be direct mast cell secretagogues. Patients with mast cell activation syndrome should receive premedication recommendations and treatment recommendations for anaphylaxis. Premedication and treatment recommendations consist of histamine and leukotriene blockade, as well as mast cell membrane–stabilizing compounds, such as ketotifen and cromolyn (Hamilton, 2018; Weiler et al., 2019). In addition to medications and foods, patients with EDS/HSD and comorbid MCAD need to identify and reduce exposure to nonimmunologic triggers, such as chemicals, stress, pollen, heat/cold, and exercise (Seneviratne et al., 2017). For patients with more recalcitrant MCAD, desensitization therapy may be appropriate, as well as use of nonsteroidal immunosuppressants and some biologic therapies, including omalizumab and possibly supplemental gamma globulin (Molderings et al., 2016; Seneviratne et al., 2017).
Glucocorticoid therapy is not recommended for patients with both EDS/HSD and MCAD (Seneviratne et al., 2017). Regular exercise to the patient’s usual limit of tolerance is recommended; however, strenuous exercise may trigger a mast cell activation flare (Seneviratne et al., 2017).
Assessment
Three criteria have been proposed for diagnosing mast cell activation syndrome: (1) typical signs and symptoms of mast cell mediator release (affecting at least two organ systems); (2) specific symptoms in six organ systems (skin, cardiovascular, gastrointestinal, respiratory, naso-ocular, and anaphalyxis); and (3) objective evidence of mast cell–derived mediator release or chronically activated mast cells, typically obtained with laboratory testing (Seneviratne et al., 2017). Elevated serum tryptase is often used in the diagnosis of mast cell activation syndrome, although symptoms of MCAD may occur without elevated tryptase. Annex Table 5-7 summarizes common methods used to diagnose MCAD.
Effects on Functioning
Patients with MCAD and EDS/HSD may experience fatigue and malaise. Both physical and psychological stress can activate mast cells. Pain is a common characteristic of MCAD that can be treated with nonsteroidal anti-inflammatory drugs, although their use needs to be tailored to the individual patient. Among the many symptoms of MCAD that may affect function are urticaria, angioedema, asthma, neurocognitive impairment, throat swelling, diarrhea, and cramping (Seneviratne et al., 2017).
Full-Body Functioning
One of the challenges of assessment of functioning, especially as it relates to SSA disability determinations, is capturing the full effect of an individual’s impairment(s) on daily activities (see NASEM, 2019). This is particularly true when a person has multiple impairments that individually do not rise to the level of severity required by SSA but collectively may do so. Given that individuals with HDCTs typically experience secondary impairments in multiple body systems, it is important to assess the collective effect of all their physical and mental impairments on their ability to function in daily life, including at work and in school. In addition, as discussed previously, some frequently experienced conditions, such as chronic pain, fatigue, mild cognitive impairment, anxiety, and depression, can affect individuals’ overall functioning. As described in Chapter 1, SSA’s disability determination process for children includes a concept called functional equivalence.
The technique for determining functional equivalence is a “whole child” approach that “accounts for all of the effects of a child’s impairments singly and in combination—the interactive and cumulative effects of the impairments—because it starts with a consideration of actual functioning in all settings” (SSA, 2009). This approach is particularly well suited to evaluating the combined effects on functioning of the many and varied impairments that often manifest in HDCTs and other multisystem disorders.
Potential Reasons
Annex Table 5-13 lists some of the potential reasons for limitations in full-body functioning among individuals with HDCTs. These include pain; weakness; fatigue; deconditioning; joint instability throughout the body; dysautonomia, including POTS; balance dysfunction; and cardiovascular, respiratory, and gastrointestinal impairments.
Assessment
A number of performance-based and self-reported measures for assessing overall physical functioning are included in Annex Table 5-13. The Bruininks-Oseretsky Test of Motor Proficiency, 2nd Edition (BOT-2) is an established performance-based measure for assessing gross and fine motor function in children and young adults (ages 4–21) (Bruininks and Bruininks, 2005). BOT-2 comprises eight subtests: fine motor precision, fine motor integration, manual dexterity, bilateral coordination, balance, running speed and agility, upper-limb coordination, and strength (Bruininks and Bruininks, 2005). A small Swedish study of children aged 8–16 years found that children with joint hypermobility scored lower on the BOT-2 balance subtest compared with the control group (Schubert-Hjalmarsson et al., 2012). The Bruininks Motor Ability Test (BMAT) is an adaptation of the BOT-2 for adults aged 40 and older (Bruininks and Bruininks, 2012). BMAT subtests include fine motor integration, manual dexterity, coordination, balance and mobility, and strength and flexibility (Bruininks and Bruininks, 2012). A small study of healthy adults aged 65–92 living in the community in Australia found scores on the fine motor integration and manual dexterity subtests of BMAT to be predictive of the participants’ level of activity and participation as assessed on several measures, while scores on the coordination, balance, and mobility subtests were not (Seaton and Brown, 2018). Similar research using validated measures for working-age adults would be informative. Other performance-based assessments that provide information about individuals’ overall physical functioning include functional capacity evaluation (Chen, 2007; Fore et al., 2015; Genovese and Galper, 2009; Jahn et al., 2004; Kuijer et al., 2012; Soer et
al., 2008) and exercise testing that includes assessment of aerobic capacity and neuromuscular performance (Liguori and American College of Sports Medicine, 2021).
The Composite Autonomic Symptom Score-31 (COMPASS-31) is a 31-item self-report questionnaire about individuals’ experience of symptoms related to dysautonomia (Sletten et al., 2012). A study aimed at differentiating severity groups among individuals with hEDS/HSD using a set of validated self-report questionnaires found that COMPASS-31 accurately differentiated individuals with more from those with less severely involved hEDS/HSD (Copetti et al., 2019).
Selected Assistive Technologies and Relevant Accommodations
The assistive technologies and accommodations that are relevant to individuals with limitations in full-body functioning will depend on the specific impairments or conditions that are affecting their physical functioning. Annex Tables 5-14 (physical functioning) and 5-15 (vision, hearing, and speech functioning) list selected assistive technologies and reasonable accommodations for specific areas of physical functioning.
Work-Related Functioning, Activities of Daily Living, and Instrumental Activities of Daily Living
Potential Reasons
Potential reasons for limitations in work activities, ADLs, and IADLs are listed in Annex Table 5-13 and are similar to those for full-body functioning.
Assessment
A number of measures can be used to perform an integrated assessment of overall physical and mental functioning (see NASEM, 2019, Chapter 4). Five such measures that provide information on work-related functioning are the Work Disability Functional Assessment Battery (WD-FAB), the Work Ability Index (WAI), the Sheehan Disability Scale (SDS), the Social and Occupational Functioning Assessment Scale (SOFAS), and the Mental Illness Research, Education, and Clinical Center version of the Global Assessment of Functioning scale (MIRECC GAF).
WD-FAB is a computerized self-report measure designed to assess work-related functioning in two domains: physical and mental health (Brandt and Smalligan, 2019; Meterko et al., 2019). WD-FAB consists of eight scales: basic mobility, upper-body function, fine motor function, community
mobility, resilience and sociability, self-regulation, communication and cognition, and mood and emotions (Marfeo et al., 2019). Content relating to physical functioning includes such activities as sitting, standing, walking, and using a wheelchair/device to move around, as well as driving; using transportation; and pushing, pulling, lifting, and carrying (Marfeo et al., 2019). Content related to mental functioning includes cognitive functioning; communication; and management of mood, emotions, and behaviors (Marfeo et al., 2019).
The WAI is a seven-item self-report questionnaire designed to measure the work capacity of individuals in an occupational health clinic environment (Ilmarinen, 2007; NASEM, 2019; Tuomi et al., 1998, p. 90). It asks respondents about their “current work ability compared with the lifetime best,” their “work ability in relation to the demands of the job,” the “number of current diseases diagnosed by a physician,” their “estimated work impairment due to diseases,” the amount of “sick leave during the past year (12 months),” their “own prognosis of work ability 2 years from now,” and “mental resources” (Ilmarinen, 2007). The responses are used to calculate a score categorizing the individual’s work capability as poor, moderate, good, or excellent. The WAI can be used to predict early retirement, work disability, absence due to sickness, and mortality relatively well (NASEM, 2019). It also can be used to identify individuals who need supportive intervention (Adel et al., 2019). Repeated administration of the WAI over time may be particularly informative.
The SDS is a five-item self-report questionnaire designed to measure the effect of symptoms due to a physical or mental health condition on an individual’s functioning in three areas: work or school, social life, and family life or home responsibilities (Sheehan, 1983). It can be used to assess change in functioning over time and has been shown to be sensitive to treatment effects in a selected group of mental health conditions, including anxiety disorders and depression (Sheehan and Sheehan, 2008).
The SOFAS provides a rating of social and occupational functioning on a scale from 0 to 100: lower scores indicate lower functioning (Rybarczyk, 2011). In contrast to the Global Assessment of Functioning scale, the SOFAS focuses on functioning independent of the severity of the person’s psychological symptoms, and it includes impairments caused by physical as well as mental disorders (Rybarczyk, 2011).
The MIRECC GAF measures occupational, social, and psychological functioning separately on three different subscales—occupational, social, and symptom—that use ratings of 0 to 100, with lower scores indicating worse functioning and greater symptom burden (Niv et al., 2007).
ADLs and IADLs are tasks typically performed by individuals in the course of everyday life. ADLs include such basic self-care tasks as “personal care and hygiene, dressing, feeding, continence management, and mobility”
(NASEM, 2019, p. 77). IADLs are “more complex tasks related to independent living in the community, such as navigating transportation options and shopping, preparing meals, managing one’s household, managing finances and medications, communicating with others, and providing companionship and mental support” (NASEM, 2019, p. 77). ADLs and IADLs can be assessed through self report, third-party report (e.g., caretaker, family member), direct observation, and/or specific assessment measures, a number of which are listed in Annex Table 5-13. The assessment of ADLs and IADLs and their relevance to work disability are discussed in detail in Functional Assessment for Adults with Disability (NASEM, 2019, pp. 76–82). Although information about individuals’ ability to perform ADLs and IADLs may help inform determinations about their ability to work, there is no evidence to support a direct correlation between ADL and IADL assessments and the ability to perform work (NASEM, 2019).
Selected Assistive Technologies and Relevant Accommodations
Annex Table 5-13 lists a number of assistive technologies and accommodations that may improve individuals’ ability to perform ADLs and IADLs, as well as work-related functioning. These include devices to improve mobility, reachers, built-up handles on home or work tools, and reorganization of or modifications to the home and workplace. The specific types of devices and accommodations needed depend on individuals’ specific impairments and the activities affected.
PHYSICAL FUNCTIONING
The physical activities addressed in Annex Tables 5-2 and 5-14 are sitting, standing, walking, strenuous physical activity, lifting (floor to waist and overhead), carrying (which usually requires the ability to stand, lift, and walk), pushing or pulling, reaching, overhead reaching, at or below the shoulder reaching, gross manipulation, fine manipulation, foot and leg controls, climbing (which may include stairs, ramps, ladders, scaffolding, ropes, etc.), and low work (including stooping, crouching, kneeling, crawling, or lying on the ground). As previously mentioned, the committee identified these activities as most relevant to SSA based on the information SSA collects about applicants and the information the U.S. Bureau of Labor and Statistics collects about the physical demands of jobs for inclusion in the Occupational Information System. The committee added “strenuous physical activity” to the list and modified the grouping of some of the other activities on the basis of their functional similarities or dissimilarities. Annex Table 5-2 provides definitions of the various physical activities along with explanations for deviations from the definitions of relevant physical
job demands provided in the ORS [Occupational Requirements Survey] Collection Manual (BLS, 2020).
Potential Reasons
The committee identified seven potential reasons for limitations in any of the physical activities listed above: (1) pain, (2) joint instability, (3) weakness, (4) balance dysfunction, (5) fatigue and deconditioning, (6) neurological compromise, and (7) orthostatic intolerance and dysautonomia (see Annex Table 5-14). The specific activities affected depend on the location of the pain, the affected joints, weakness, and/or neurological compromise experienced by the individual. For example, instability in the cervical or lumbar spine, pelvis, and knees, as well as weakness and balance dysfunction affecting the trunk, can limit an individual’s ability to sit, especially uninterrupted for prolonged periods of time. Instability in the cervical or upper-extremity joints and weakness in the arms and hands can limit an individual’s ability to perform activities requiring fine manipulation, including keyboarding. Gross and fine manipulation may also be affected by coordination deficits. In addition to the effects of musculoskeletal and neurological impairments, such activities as walking and strenuous physical activity can be limited by cardiac and/or respiratory dysfunction and exercise intolerance. Recovery from major aortic surgery can take up to a year depending on extent of aortic replacement, further restricting participation during that time. Cardiac and aortic dysfunction also can restrict an individual’s ability to lift objects from floor to waist or overhead.
Physical activity guidelines and restrictions for individuals with MFS and related disorders must be tailored to the specific person. However, general guidelines include avoidance of intense isometric exercise, such as occurs when straining to lift a heavy weight; contact sports that can lead to blows to the head; activities that involve rapid acceleration and deceleration over short distances (sprinting); activities that involve rapid changes in pressure (e.g., scuba diving); and exercise to the point of exhaustion (Paris and Brigham and Women’s Hospital, 2008; Marfan Foundation, 2017). Metabolic equivalent of task (MET), or simply metabolic equivalent, is a physiological measure expressing the energy cost (or calories expended) of physical activities as a multiple of resting energy consumption. Generally, it is recommended that individuals with MFS and related disorders keep the intensity of their physical activity in the low to moderate range (i.e., < 6 METs) (Marfan Foundation, 2017). The physical activity guidelines from The Marfan Foundation (2017, p. 3) include a table of common physical and recreational activities that fall into light (< 3 METs), moderate (3–6 METs), and vigorous (> 6 METs) categories of intensity. Also included is a table of competitive sports and athletic activities organized by risk of
contact and intensity (Marfan Foundation, 2017, p. 7). The mental and physical health benefits of exercise are well known, but it is important to tailor the type and intensity of physical activity to the specific needs of individuals with HDCTs. Especially for children and adolescents, the benefits of physical activities often extend beyond the physical. Participation in spontaneous and organized physical activities, from playing tag and climbing trees to engaging in contact sports, gymnastics, and dance, is often the center of social interaction and central to the psychosocial and emotional well-being of many children and adolescents. Research on the relative benefits versus risks of participation in common physical activities is therefore important to better inform disease management in these age groups.
Maintaining a static position uninterrupted, such as sitting (especially the prolonged sitting often required to perform sedentary work or participate in a classroom) or standing for a prolonged period of time can be particularly problematic for individuals with HDCTs. Weak connective tissue and limited functionality of primary stabilizers (ligaments and tendons) can limit the ability to be erect in sitting or standing or for travel, and POTS can limit the ability to stand for extended periods. Jobs that might be considered sedentary but require an employee to move frequently between a seated and standing position may also be difficult for individuals with orthostatic intolerance. The freedom to move about and change position as needed (e.g., sitting to standing, walking in place) is important for these individuals to maintain function and reduce impairment. Conditions such as POTS, discussed earlier, can limit an individual’s ability to remain in a seated position for even a few minutes or to function effectively while sitting or standing because of mild cognitive impairment. Individuals with EDS/HSD and other HDCTs may be unable to perform repetitive motions, including the fine manipulations, writing, and, in some cases, keyboarding that are often integral to sedentary work and school activities, over an extended period of time.
It is important to remember that the performance of a specific physical activity rarely if ever occurs independently of other physical activities. Annex Table 5-14 notes some of the overlaps among physical activities. Also, as previously mentioned, the committee includes lying down on the ground under “low work,” along with stooping, crouching, kneeling, and crawling. This contrasts with the collection of occupational data on “sitting,” which includes “active lying down. For example, a mechanic lying on a dolly working underneath a vehicle is sitting” (BLS, 2020, p. 112). Although lying on a raised surface (e.g., a bed) may be grouped with sitting, sitting is distinct from lying down on the ground (e.g., lying on a dolly underneath a vehicle). From a functional perspective, lying on the ground has more in common with other low work activities in that it includes the need to get up and down from the ground and potentially squirming around to
do work while on the ground. These are difficult tasks that are equivalent to the other low work activities.
Assessment
Annex Table 5-14 lists performance-based and self-reported outcome measures that provide information relevant to an individual’s ability to perform specific physical activities. Because of the importance of matching an individual’s functional capacities to specific job requirements, a functional capacity evaluation is advised for individuals with hEDS/HSD (De Baets et al., 2021). Alternatively, specific function testing performed by a trained clinician (e.g., physical therapist, occupational therapist, exercise physiologist), directed at an individual’s ability to perform the activities of interest, provides information about the person’s ability to sustain those activities for the length of time required to perform a specific job or participate in classroom or other activities. When extrapolating from the testing environment to the workplace or school, it is important to remember that environmental conditions can affect individuals’ symptoms and functioning. Performance at work and school, where physical, cognitive, and emotional stressors are often greater than in the testing environment, may be affected in ways not observed during testing.
Selected Assistive Technologies and Relevant Accommodations
Annex Table 5-14 lists a variety of assistive technologies and accommodations that can assist individuals in performing specific physical activities. Braces and other supports can assist with sitting, and allowing students or employees to alternate between sitting and other positions and to take rest breaks as needed can help them participate successfully in school and work. Specialized pencil/pen grips and alternative keyboards may facilitate handwriting and keyboarding. Students may benefit from a number of other school-based accommodations as well (SchoolToolkit, 2022), which can be formalized in a 504 plan or individualized education program. The use of certain assistive devices, in particular mobility devices to assist with standing and walking, including wheelchairs, can be very stressful for upper-extremity joints and may interfere with those activities requiring use of the upper extremities (e.g., lifting or carrying while using crutches). Similarly, ambulation devices that allow one to move well on a level or sloped surface may not be usable for climbing or ascending steep inclines.
VISION, HEARING, AND SPEECH FUNCTIONING
To a greater or lesser extent, vision, hearing, and speech functions may be affected in people with HDCTs (see Annex Tables 5-11 and 5-15).
Vision
Near visual acuity is defined as “clarity of vision at approximately 20 inches or less, as when working with small objects or reading small print” (BLS, 2020, p. 154). Close work, such as reading, writing, computer use, and manipulation of small objects, requires not only near visual acuity but also the ability of the eyes to work together as a team (binocular vision). When one’s eyes do not work together because of accommodative or vergence dysfunction, one’s ability to perform tasks requiring near vision (close work) may be impaired even when vision is normal in each eye independently (monocular vision). Difficulties performing close work can affect performance in school, recreational activities (sports, riding a bicycle), and jobs requiring close work.
Far visual acuity is defined as “clarity of vision at a distance of 20 feet or more, involving the ability to distinguish features of a person or objects at a distance” (BLS, 2020, p. 154). Peripheral vision refers to “what is seen above, below, to the left or right by the eye while staring straight ahead” (BLS, 2020, p. 154). Such tasks as driving, reading a blackboard, or participating in certain sports require far visual acuity. Driving and participating in certain sports are examples of tasks that also require peripheral vision.
Potential Reasons
A number of potential reasons for limitations in near and far visual acuity and peripheral vision are listed in Annex Table 5-15. They range from uncorrected refractive error to lens dislocation, retinal detachment or scarring, and cataract formation.
Assessment
Assessment of near and far visual acuity is performed using eye charts (e.g., Snellen, Bailey-Lovie) at a distance and handheld charts, respectively. Convergence (the ability of the eyes to work together) is assessed through orthoptic evaluation. One test of convergence asks the subject to maintain focus on a near target at a fixed distance while passing progressively stronger base-out prisms in front of one eye until the person experiences double vision or the examiner sees one of the eyes drift outward. Peripheral vision is assessed using kinetic or semiautomated kinetic perimetry to create
maps of an individual’s visual field. Functional Assessment for Adults with Disabilities includes a more detailed discussion of visual functioning and assessment (NASEM, 2019, pp. 128-133).
Selected Assistive Technologies and Relevant Accommodations
Assistive technologies for individuals with vision impairments include low-vision devices (refractive lenses), over-the-counter reading glasses to help with accommodative insufficiency, and base-in prism glasses to help with double vision during near work when impairment is related to convergence insufficiency. Other interventions include auditory replacements for vision tasks, glare-reducing equipment, orientation and mobility training (for impaired far and peripheral vision), and such modifications as sitting closer to the blackboard/screen in a classroom.
Hearing
Hearing is defined as the “ability to hear, understand, and distinguish speech and/or other sounds” (BLS, 2020, p. 149). Hearing is typically needed for jobs and schooling requiring communication, one-on-one and in group settings, in person or through video conferencing. It also is needed when a job requires use of a telephone or similar device, such as a radio, walkie-talkie, intercom, or public address system, or the ability to hear such sounds as machinery alarms and equipment sounds (BLS, 2020).
Potential Reasons
Hearing loss generally is classified as sensorineural, conductive, or a mix of the two, all of which may be seen in individuals with EDS/HSD, MFS, and Loeys-Dietz syndrome (LDS). People with EDS/HSD also may experience tinnitus, which refers to hearing sounds (e.g., ringing, clicking) in the absence of a corresponding external noise. Some people with tinnitus experience a muffling or distortion of external sounds (Møller, 2007).
Assessment
Performance-based measures for assessing hearing include pure tone audiometry (McBride et al., 1994; Yueh et al., 2003), speech recognition in noise testing (Giguère et al., 2008; Laroche et al., 2003), and internet- and telephone-based screening (Smits et al., 2004; Watson et al., 2012). Self-reported outcome measures for individuals with hearing impairments include the Hearing Handicap Inventory for Adults (Newman et al., 1990) and the Speech, Spatial, and Qualities of Hearing Scale (Gatehouse and
Noble, 2004). Assessment of hearing impairments and their effects on individuals’ functioning are discussed in Functional Assessment for Adults with Disabilities (NASEM, 2019, pp. 133–143).
Selected Assistive Technologies and Relevant Accommodations
A 2017 National Academies report provides an analysis of selected assistive technologies and devices, including products and technologies pertaining to hearing (NASEM, 2017). Such technologies include hearing aids, personal sound amplification products, remote microphone hearing assistive technology, captioning, and telecommunications relay services. Environmental modifications (e.g., to improve acoustics) are also helpful.
Speech
Speech is defined as the expression or exchange of “ideas by means of the spoken word to impart oral information…accurately, loudly, or quickly” (BLS, 2020, p. 149). Although functional communication need not involve speech (but may involve, for example, alternative expressive modalities, nonverbal interactions, written language, and social communication), speech is necessary for certain jobs and is important if children are to be able to participate fully in school, including interaction with their peers. Language is another component of functional communication. Whereas speech comprises the physical processes of forming word sounds to convey a message, language is defined as the use of words, grammar rules, and the like to construct the content of the message.
Potential Reasons
Many factors contribute to communication, including the skills of the individual and the communication partner(s), as well as environmental conditions (e.g., background noise). With respect to the individual, “physical factors specific to communication (articulation accuracy, speaking rate, voice quality, loudness, fluency, effort, and fatigue) affect the intelligibility and comprehensibility of speech production” (NASEM, 2019, p. 144). Functional speech among individuals with HDCTs may be affected by temporomandibular joint dysfunction, laryngeal dysfunction, oral and dental pain, and vocal fatigue. Individuals with EDS/HSD may experience “painless dysphonia, fluctuating hoarseness, weak voice, dysphagia, recurrent episodes of laryngospasm, and subglottic stenosis” (Chohan et al., 2021, citing Arulanandam et al., 2017). Dysphonia among individuals with EDS/HSD may be attributable, at least in part, to “laxity, hypotonia, discoordination or decreased movement of the vocal cords, as well as reduced mobility of
the cricoarytenoid joint” (Chohan et al., 2021, citing Arulanandam et al., 2017; Castori et al., 2010; Hunter et al., 1998). Individuals with cervical medullary syndrome and Chiari malformation may also experience dysarthria (Henderson et al., 2019).
With respect to language, “mental factors specific to communication at the individual level (receptive, expressive, and pragmatic language skills) affect message comprehension” (NASEM, 2019, p. 144). For example, difficulties with word finding, experienced by some individuals with mild cognitive impairment, affect language.
Assessment
Annex Table 5-15 lists a selection of measures of speech function, including measures of intelligibility, dysarthria, and apraxia, as well as several communication scales. A more complete discussion of speech functioning in the context of work, along with assessment measures, is included in Functional Assessment for Adults with Disabilities (NASEM, 2019, pp. 143–157).
Selected Assistive Technologies and Relevant Accommodations
A number of technologies can assist individuals with functional communication when speech is impaired. Personal voice amplification devices may be used to increase the volume of one’s natural speech, and a wide variety of augmentative and alternative communication devices can replace oral communication if necessary (see NASEM, 2017, Chapter 6). Environmental modifications may help as well. For example, dry or dusty environments can exacerbate speech difficulties among individuals with EDS/HSD.
MENTAL FUNCTIONING
The committee focused on the mental activities included in Annex Table 5-16 because they are areas of mental functioning of particular interest to SSA for adults and children aged 3–18 years. The following mental activities are found in Paragraph B of SSA’s Listing of Impairments for mental disorders (SSA, n.d.-c, n.d.-d): understand, remember, and apply information; concentrate, persist, or maintain pace; problem solve; interact with others; and adapt or manage oneself. Annex Table 5-2 provides definitions for each of these areas of mental functioning. Difficulties in these areas can affect quality of life in individuals with HDCTs.
A study of executive functioning and quality of life in adults with MFS found that “mental fatigue, commitment, instructions, problem solving, prospective memory, impulsivity, and flexibility” were all reliable predictors
of satisfaction with quality of life (Ratiu et al., 2018). Cognitive dysfunction also has been reported in patient populations with conditions associated with HDCTs, including POTS (Raj et al., 2018; Ross et al., 2013; Wells et al., 2020) and CFS (Ocon, 2013). Such patients often complain of “brain fog,” a type of cognitive dysfunction involving mild cognitive impairment. Patient-reported descriptors of “brain fog” include forgetfulness, difficulty thinking, difficulty focusing, feeling cloudy, difficulty finding the right words/communicating, mental fatigue, slowness, mind going blank, feeling “spacey,” and difficulty processing what others say (Ross et al., 2013). Individuals reporting “brain fog” have shown mild to moderate cognitive impairment (Raj et al., 2018). Specific deficits have been found in short-term and working memory, selective attention, cognitive processing, reaction times, and executive functioning, although specific results vary among studies (Arnold et al., 2015; Ocon, 2013; Wells et al., 2020). Chapman (2020) reports effects on verbal recall and ability to do basic math, as well as short-term memory and concentration; word choice and language may also be affected.
Ross and colleagues (2013) found that 96 percent of respondents (aged 14–29) with POTS reported “brain fog,” with 67 percent experiencing it daily. The majority of respondents said their symptoms adversely affected “their ability to complete schoolwork (86%), be productive at work (80%), and participate in social activities (67%).” These findings are consistent with other reports that individuals with “brain fog” “often complain of an inability to perform day-to-day tasks, organize thoughts, or hold a conversation,” as well as difficulty with focus, learning and retaining information, and maintaining employment (Chapman, 2020).
A recent review of literature on the psychological burden associated with EDS/HSD found the highest prevalence for “language disorders (63.2%), attention-deficit/hyperactivity disorder (ADHD) (52.4%), anxiety (51.2%), learning disabilities (42.4%), and depression (30.2%),” although there often is great variability among studies in the prevalence reported (Kennedy et al., 2022). The reported prevalence for depression, for example, ranged from 11.1 to 30.2 percent, while that for anxiety ranged from 9.0 to 51.2 percent (Kennedy et al., 2022). Anxiety can manifest as feeling nervous, restless, or tense; worry; brooding—trouble concentrating or thinking about anything except the present worry; anticipatory anxiety; a sense of dread; task avoidance; and irritability, as well as physical symptoms (Mayo Clinic, 2022a; NLM, 2020). Depressive episodes manifest in symptoms (sadness, irritability, and emptiness; loss of pleasure or interest in activities) that persist for most of the day, almost every day, for at least 2 weeks (WHO, 2022). Other symptoms may include trouble concentrating, a feeling of excessive guilt or low self-worth, and hopelessness, in addition to physical symptoms (Mayo Clinic, 2022b; WHO, 2022). Anxiety
and depression, which may coexist, can significantly interfere with daily activities, including participation in school and work; personal and social activities; and relationships with family, friends, teachers, coworkers, and others (Mayo Clinic 2022b; WHO, 2022).
Potential Reasons
Importantly, both physical and psychiatric conditions contribute to decrements in mental functioning. Chronic pain, fatigue, cognitive impairments, depression, mood disorders, anxiety, and impulsivity, individually and collectively, can affect mental functioning in the areas identified (see Annex Table 5-16).
Impaired cerebral blood flow associated with POTS (Ross et al., 2013; Wells et al., 2020); chronic inflammatory processes, which may disrupt the normal neuroimmune communication that is important to learning and memory (Mackay, 2015); and fatigue and poor sleep quality (Ross et al., 2013) may play a role in the cognitive dysfunction experienced by patients. Orthostatic and cognitive stressors, such as prolonged standing and prolonged concentration, have been reported to trigger or worsen cognitive dysfunction (Ocon, 2013; Ross et al., 2013), although some patients have reported that symptoms continue even after they return to a supine position, and others have reported that cognitive stressors (e.g., prolonged concentration) trigger symptoms while they are lying down (Ross et al., 2013).
Research on the effects of anxiety and depression on work and school performance in populations without HDCTs shows that both conditions can adversely affect performance (Beck et al. 2019; Jaycox et al., 2009; Mazzone et al., 2007; Plaisier et al., 2010), although depression may have a larger effect than anxiety (Plaisier et al., 2010). Plaisier and colleagues (2010) found that the risk of absenteeism and decreased work performance was greater among individuals who had more severe anxiety and depression. Beck and colleagues (2019) also found a relationship between productivity loss and severity of depression based on PHQ-9 scores, with even minor levels of depression being associated with decreased work function. In another study, teenagers with versus those without depression reported significantly greater impairment in academic, peer, and family functioning and physical health-related quality of life, as well as more days of impairment (Jaycox et al., 2009). Anxiety also adversely affects school performance and is associated with impaired memory and cognitive functions (Mazzone et al., 2007). Anxiety may interfere as well with the development of social skills, social life, and overall well-being (Mazzone et al., 2007).
Assessment
Annex Table 5-16 lists a variety of psychological and neuropsychological measures for assessing individuals’ functioning in each of the areas of interest. More generally, as discussed in the section on work-related functioning, ADLs, and IADLs, the SDS has been widely used to assess the effects of symptoms of different mental health conditions on an individual’s functioning at work or in school, in social life, and in family or home responsibilities (Sheehan, 1983). In addition, the WD-FAB is designed to assess cognitive functioning; communication; and management of mood, emotions, and behaviors relevant to work (Marfeo et al., 2019).
Selected Assistive Technologies and Relevant Accommodations
Annex Table 5-16 lists a number of accommodations that may support or improve individuals’ mental functioning in the specified areas. Providing short, step-by-step instructions and breaking work tasks down into sequential steps is helpful, along with providing a written summary of the steps or recording them for playback by the individual as needed. Arranging for work to be performed in a quiet area without distractions and allowing individuals to sit or stand at will and take breaks as needed can also improve functioning.
HERITABLE DISORDERS OF CONNECTIVE TISSUE AND THE U.S. SOCIAL SECURITY ADMINISTRATION’S LISTING OF IMPAIRMENTS
The statement of task for this study asked the committee to “identify [for the selected HDCTs] non-exertional physical limitations (e.g., balancing or using the upper extremities for fine or gross movements) and mental limitations (e.g., cognitive or behavioral) that are equivalent in severity to the standard represented in the listings (i.e., that would prevent any gainful activity) but are not captured by currently existing listings and are not currently reflected in SSA’s disability grid rules.”
For SSA, nonexertional limitations occur when “limitations and restrictions imposed by [an individual’s] impairment(s) and related symptoms, such as pain, affect only [their] ability to meet the demands of jobs other than the strength demands.”3 Examples include “difficulty functioning because [one is] nervous, anxious, or depressed”; “difficulty maintaining attention or concentrating”; “difficulty understanding or remembering detailed instructions”; “difficulty in seeing or hearing”; “difficulty tolerating
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3 20 CFR 404.1569a.
some physical feature(s) of certain work settings, e.g., one cannot tolerate dust or fumes”; and “difficulty performing the manipulative or postural functions of some work such as reaching, handling, stooping, climbing, crawling, or crouching.”4
It is clear from the variety of physical and mental secondary impairments throughout all body systems, related symptoms (e.g., pain, fatigue), and potential environmental triggers experienced by individuals with HDCTs that they can experience nonexertional limitations in any of the above areas. In some cases, the limitations may be sufficiently severe as to preclude the individual’s participation in any gainful activity. In other cases, the combined effects of an individual’s qualifying physical and/or mental secondary impairments may limit function sufficiently to preclude participation in work “in an ordinary work setting, on a regular and continuing basis, and for 8 hours a day, 5 days a week, or an equivalent work schedule” (SSA, 2021) or, for children, to cause “marked and severe functional limitations.”5
Some individuals with HDCTs may qualify for SSA disability benefits at the listing-level step in the determination process on the basis of the secondary impairment(s) they are experiencing, rather than the HDCT itself. With the exception of MFS, which is identified under the cardiovascular listing 4.10 (aneurysm of aorta or major branches), HDCTs are not currently specified in the listings; for both adults and children, SSA disability claims related to HDCTs are evaluated under listings for the affected body system. Annex Table 5-17 includes some of the listings that may apply to certain individuals with HDCTs, as well as notes indicating special considerations. Examples of musculoskeletal SSA listings that could apply directly to some applicants with an HDCT include
Joint and soft-tissue injury or abnormalities and pain are very common in individuals with HDCTs and hypermobility, resulting in significant functional limitations. It is important to note that certain abnormalities
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4 20 CFR 404.1569a.
5 20 CFR 416.906.
may not be seen on standard imaging, necessitating the use of specialized imaging (e.g., flexion or extension imaging; magnetic resonance imaging [MRI], potentially upright, if tolerated; dynamic or soft-tissue imaging). In addition, as discussed previously, individuals with versus those without HDCTs are more likely to have poor outcomes with major surgery, especially if their HCDT was not previously recognized or taken into account in performing the surgery and providing aftercare. Wound healing is slow in many HDCTs, and wound dehiscence may occur despite excellent surgical and postoperative care. Some patients are unable to engage fully in postoperative therapy because of such HDCT-associated problems as fatigue, orthostatic intolerance, MCAD, depression, mild cognitive impairment, gastrointestinal disorders, or other musculoskeletal issues, which may further comprise surgical outcomes. As a result, surgical intervention, especially repeated surgery, for soft-tissue injuries or abnormalities may be contraindicated in some people with HDCTs even if it would be standard treatment for someone without an HDCT. The absence of surgery therefore need not imply that the person’s functional limitations are any less severe. Further, individuals with significant upper-extremity involvement may not be candidates for assistive technology to aid mobility because they would not be able to use it effectively and therefore may not have been prescribed such a device.
Listings in other body systems that may apply directly to some individuals with HDCTs include
The relationship between HDCTs and immune system dysfunction is a subject of ongoing research. It is clear that immune system dysfunction (e.g., MCAD) mediates HDCT-related secondary impairments in multiple
body systems. Criteria in two of the listings for immune system disorders are especially relevant to the multisystem presentation and symptoms of HDCTs. The specific disorders listed—systemic lupus erythematosus and Sjogren’s syndrome—are central to each set of criteria but are not common to HDCTs. The criteria listed for these disorders include
-
Involvement of two or more organs/body systems, with:
- One of the organs/body systems involved to at least a moderate level of severity; and
- At least two of the constitutional symptoms or signs (severe fatigue, fever, malaise, or involuntary weight loss).
OR
-
Repeated manifestations of [the listed disorder], with at least two of the constitutional symptoms or signs (severe fatigue, fever, malaise, or involuntary weight loss) and one of the following at the marked level:
- Limitation of activities of daily living.
- Limitation in maintaining social functioning.
- Limitation in completing tasks in a timely manner due to deficiencies in concentration, persistence, or pace. (SSA, n.d.-b, 14.02, 14.10)
Given that individuals with HDCTs typically experience physical and mental secondary impairments in multiple body systems, it is important to assess the collective effect of all their physical and mental impairments on their ability to function in daily life, including at work and in school. This is particularly true when a person has multiple impairments that individually do not rise to the level of severity required by SSA but collectively may do so. The concept of functional equivalence used by SSA in some disability determinations in children is particularly well suited to evaluating the combined effects on an applicant’s functioning of the many and varied impairments that often manifest in HDCTs and other multisystem disorders.
FINDINGS AND CONCLUSIONS
Findings
5-1. The number, type, and severity of the physical and mental secondary impairments experienced by an individual with a heritable disorder of connective tissue (HDCT) drive the person’s functioning and potential disability.
5-2. Environmental factors (e.g., temperature extremes, noise, vibration, atmospheric conditions, inhaled or skin irritants) can have significant adverse effects on function for some individuals with HDCTs.
5-3. Both physical and mental conditions can precipitate or exacerbate decrements in physical and mental functioning in individuals with HDCTs.
5-4. Chronic pain, chronic fatigue, and mild cognitive impairment are some of the most common and potentially disabling manifestations of the Ehlers-Danlos syndromes (EDS), especially hypermobile EDS (hEDS), hypermobility spectrum disorders (HSD), and Marfan syndrome (MFS).
5-5. A complex relationship exists among pain, fatigue, postural orthostatic tachycardia syndrome, and mast cell activation disease.
5-6. Pain can interfere with all types of physical activities that may be entailed in work or school, including sedentary activities. Pain also has an effect on cognitive functioning.
5-7. Fatigue associated with EDS/HSD and MFS can result in a number of physical and mental functional impairments that affect daily activities, including participation in work and physical activities.
5-8. Mild cognitive impairment can adversely affect participation in school, work, and social activities.
5-9. A challenge in assessment of functioning is capturing the full effect of individuals’ impairments on their daily activities, including at work and in school. This is particularly true when a person has multiple impairments.
5-10. Numerous validated performance-based and self-reported measures are available for assessing physical and mental functioning, including several that can be used to perform an integrated assessment of an individual’s overall physical and mental functioning.
5-11. Performance of a specific physical activity rarely if ever occurs independently of other physical activities.
5-12. Performance at work and in school, where physical, cognitive, and emotional stressors are often greater than in the testing environment, may be affected in ways not observed during testing.
5-13. Physical activity guidelines and restrictions for individuals with HDCTs need to be tailored to the specific person.
5-14. General physical activity guidelines exist for people with MFS and related disorders, such as avoidance of intense isometric exercise, contact sports that can lead to blows to the head, activities that involve rapid acceleration and deceleration over short distances (sprinting) or rapid changes in pressure (e.g., scuba diving), and exercise to the point of exhaustion.
5-15. Depending on a person’s underlying impairment(s), assistive technologies and relevant accommodations can improve physical and mental functioning in some cases.
5-16. Some of the listings in SSA’s Listing of Impairments—Adult Listings include severity criteria for some of the secondary impairments that may be experienced by individuals with HDCTs such as MFS, EDS, and related disorders.
5-17. Individuals with HDCTs may experience significant variability in their physical and/or mental secondary impairments from day to day or even within a single day. This variability is often unpredictable and may limit the ability to sustain gainful employment.
Conclusions
5-1. Given that individuals with HDCTs typically experience physical and mental secondary impairments in multiple body systems, it is important to assess the collective effect of all their physical and mental impairments on their ability to function in daily life, including at work and in school.
5-2. Accurately assessing the full effect of an individual’s impairment(s) is especially important for SSA disability determinations. This is particularly true when a person has multiple impairments that individually do not rise to the level of severity required by SSA but collectively may do so. The concept of functional equivalence used by SSA in some disability determinations in children is particularly well suited to evaluating the combined effects on an applicant’s functioning of the many and varied impairments that often manifest in HDCTs and other multisystem disorders.
5-3. Because of the importance of matching an individual’s functional capacities to specific job requirements, functional capacity evaluation or specific function testing, performed by a trained clinician and directed at an individual’s ability to perform the activities of interest, is suggested to provide information about the person’s ability to sustain those activities for the length of time required to perform a specific job or participate in classroom or other activities.
5-4. When extrapolating from the testing environment to the workplace or school, it is important to take into account specific environmental conditions that can affect the individual’s symptoms and functioning.
5-5. Some of SSA’s Listing of Impairments—Adult Listings apply directly to secondary impairments experienced by individuals with HDCT syndromes and could be used to evaluate disability in those individuals. Other listings, with some modification, could apply to individuals with certain secondary impairments associated with their HDCTs.
5-6. The combined effects of an individual’s physical and/or mental secondary impairments may limit function with a degree of severity sufficient to preclude the ability to participate in work on a “regular and continuing basis” (8 hours per day, 5 days per week, or an equivalent work schedule) or, for children, to cause “marked and severe functional limitations.”
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Williams, K. T. 2018. Expressive Vocabulary Test, 3rd ed. https://www.pearsonassessments.com/store/usassessments/en/Store/Professional-Assessments/Academic-Learning/Brief/Expressive-Vocabulary-Test-%7C-Third-Edition/p/100001982.html (accessed January 12, 2022).
Willy, R. W., L. T. Hoglund, C. J. Barton, L. A. Bolgla, D. A. Scalzitti, D. S. Logerstedt, A. D. Lynch, L. Snyder-Mackler, and C. M. McDonough. 2019. Patellofemoral pain. Journal of Orthopaedic and Sports Physical Therapy 49(9):CPG1-CPG95. https://doi.org/10.2519/jospt.2019.0302.
Wyller, V. B., J. A. Evang, K. Godang, K. K. Solhjell, and J. Bollerslev. 2010. Hormonal alterations in adolescent chronic fatigue syndrome. Acta Paediatrica 99(5):770-773. https://doi.org/10.1111/j.1651-2227.2010.01701.x.
Yasuda, S., K. Imoto, K. Uchida, D. Machida, H. Yanagi, T. Sugiura, K. Kurosawa, and M. Masuda. 2013. Successful endovascular treatment of a ruptured superior mesenteric artery in a patient with Ehlers-Danlos syndrome. Annals of Vascular Surgery 27(7):e971-e975. https://doi.org/10.1016/j.avsg.2013.01.004.
Yorkston, K. M., and D. R. Beukelman. 1984. Assessment of intelligibility of dysarthric speech. Austin, TX: PRO-ED.
Yueh, B., N. Shapiro, C. H. MacLean, and P. G. Shekelle. 2003. Screening and management of adult hearing loss in primary care: Scientific review. JAMA 289(15):1976-1985. https://doi.org/10.1001/jama.289.15.1976.
Zhang, L., and T. F. Yuan. 2019. Exercise and substance abuse. International Review of Neurobiology 147:269-280. https://doi.org/10.1016/bs.irn.2019.07.007.
ANNEX TABLE 5-1
Levels of Work Based on Physical Exertion Requirements
| Level of Work | Definition |
|---|---|
| Sedentary | Sedentary work involves “lifting no more than 10 pounds at a time and occasionally lifting or carrying articles like docket files, ledgers, and small tools” (SSA, n.d.-e). Although a sedentary job is defined as one that involves sitting, |
|
a certain amount of walking and standing is often necessary in carrying out job duties. Jobs are sedentary if walking and standing are required occasionally and other sedentary criteria are met. By its very nature, work performed primarily in a seated position entails no significant stooping. Most unskilled sedentary jobs require good use of the hands and fingers for repetitive hand-finger actions. |
|
|
“Occasionally” means occurring from very little up to one-third of the time. Since being on one’s feet is required “occasionally” at the sedentary level of exertion, periods of standing or walking should generally total no more than about 2 hours of an 8-hour workday, and sitting should generally total approximately 6 hours of an 8-hour workday. Work processes in specific jobs will dictate how often and how long a person will need to be on his or her feet to obtain or return small articles. (SSA, n.d.-e; see also CFR § 416.967) |
|
| Light | Light work involves |
|
lifting no more than 20 pounds at a time with frequent lifting or carrying of objects weighing up to 10 pounds. Even though the weight lifted in a particular light job may be very little, a job is in this category when it requires a good deal of walking or standing—the primary difference between sedentary and most light jobs. A job is also in this category when it involves sitting most of the time but with some pushing and pulling of arm-hand or leg-foot controls, which require greater exertion than in sedentary work; e.g., mattress sewing machine operator, motor-grader operator, and road-roller operator (skilled and semiskilled jobs in these particular instances). Relatively few unskilled light jobs are performed in a seated position. |
|
|
“Frequent” means occurring from one-third to two-thirds of the time. Since frequent lifting or carrying requires being on one’s feet up to two-thirds of a workday, the full range of light work requires standing or walking, off and on, for a total of approximately 6 hours of an 8-hour workday. Sitting may occur intermittently during the remaining time. The lifting requirement for the majority of light jobs can be accomplished with occasional, rather than frequent, stooping. Many unskilled light jobs are performed primarily in one location, with the ability to stand being more critical than the ability to walk. They require use of arms and hands to grasp and to hold and turn objects, and they generally do not require use of the fingers for fine activities to the extent required in much sedentary work. (SSA, n.d.-e; see also CFR § 416.967) |
|
| Level of Work | Definition |
|---|---|
| Medium | Medium work involves |
|
lifting no more than 50 pounds at a time with frequent lifting or carrying of objects weighing up to 25 pounds. A full range of medium work requires standing or walking, off and on, for a total of approximately 6 hours in an 8-hour workday in order to meet the requirements of frequent lifting or carrying objects weighing up to 25 pounds. As in light work, sitting may occur intermittently during the remaining time. Use of the arms and hands is necessary to grasp, hold, and turn objects, as opposed to the finer activities in much sedentary work, which require precision use of the fingers as well as use of the hands and arms. |
|
|
The considerable lifting required for the full range of medium work usually requires frequent bending-stooping. (Stooping is a type of bending in which a person bends his or her body downward and forward by bending the spine at the waist.) Flexibility of the knees as well as the torso is important for this activity. (Crouching is bending both the legs and spine in order to bend the body downward and forward.) However, there are relatively few occupations in the national economy which require exertion in terms of weights that must be lifted at time (or involve equivalent exertion in pushing and pulling), but are performed primarily in a sitting position, e.g., taxi driver, bus driver, and tank-truck driver (semiskilled jobs). In most medium jobs, being on one’s feet for most of the workday is critical. Being able to do frequent lifting or carrying of objects weighing up to 25 pounds is often more critical than being able to lift up to 50 pounds at a time. (SSA, n.d.-e; see also CFR § 416.967) |
|
| Heavy | “Heavy work involves lifting no more than 100 pounds at a time with frequent lifting or carrying of objects weighing up to 50 pounds” (CFR § 416.967). |
| Very heavy | “Very heavy work involves lifting objects weighing more than 100 pounds at a time with frequent lifting or carrying of objects weighing 50 pounds or more” (CFR § 416.967). |
SOURCES: SSA, n.d.-e; CFR § 416.967.
ANNEX TABLE 5-2
Physical Activities; Vision, Hearing, and Speech; and Mental Activities
| Activity | Definition |
|---|---|
| Physical Activities | |
| Sitting | For the purpose of collecting occupational data, the U.S. Bureau of Labor Statistics considers sitting to be present |
|
when any of the following conditions exists:
From a functional perspective, however, sitting as a physical activity involves resting one’s lower body (buttocks) on a seat or the ground, while maintaining one’s upper body (torso, neck, head) in an upright position. In addition to strong neck, shoulder, and core muscles, sitting requires balance and good proprioception. Although lying on a raised surface (e.g., a bed) may be grouped with sitting, sitting is distinct from lying down on the ground (e.g., lying on a dolly underneath a vehicle), which this report groups under low work. |
|
| Standing | For the purpose of collecting occupational data, the Occupational Requirements Survey distinguishes only between sitting (as defined previously) and standing/walking defined as “whenever workers are not sitting or lying down,” including “time spent stooping, crawling, kneeling, crouching, or climbing” (BLS, 2020, p. 112). In other words, “a worker is always either sitting or standing/walking” (BLS, 2020, p. 112). |
| From a functional perspective, standing is distinct from walking, which in turn is distinct from low work (stooping, crawling, kneeling, crouching), or climbing. For the purpose of this report, standing is defined as being “in an upright position with all of [one’s] weight on [one’s] feet” (Stand, n.d.). | |
| Walking | Moving along on foot or advancing by steps, with one foot always on the ground. |
| Distance (long or short) and surface type (uneven, rough) can affect an individual’s ability to walk. | |
| Strenuous physical activity | Strenuous physical activity captures activities that require exertion and stamina—for example, running, jumping, swimming, throwing, catching, and the like. It potentially includes all other physical activities, in addition to running and other impact activities. |
| Lifting (floor to waist and overhead) | Use of upper and/or lower extremities to raise or lower an object from one level to another, including upward pulling (BLS, 2020, p. 118). |
| Carrying | “Transporting an object, usually by holding it in the hands or arms, or wearing it on the body, usually around the waist or upper torso” (BLS, 2020, p. 118). |
| Carrying usually also requires the ability to stand, lift, and walk. | |
| Activity | Definition |
|---|---|
| Pushing/pulling | Use of upper and/or lower extremities to exert force upon an object so that the object moves away from or toward the origin of the force (BLS, 2020, p. 125). |
| Reaching | “Extending the hand(s) and arm(s) in any direction, requiring the straightening and extending of the arm(s) and elbow(s) and the engagement of the shoulder(s)” (BLS, 2020, p. 130). |
| Reaching may require standing. | |
| Overhead reaching | Extending the arm(s) with the hand(s) higher than the head and (1) the elbow is bent and the angle at the shoulders is about 90 degrees or more or (2) the elbow is extended and the angle at the shoulder is about 120 degrees or more (BLS, 2020, p. 130). |
| Overhead reaching requires neck extension and may require standing. | |
| At/below the shoulder reaching | Reaching that does not meet the threshold for overhead reaching described above (BLS, 2020, p. 130). |
| At/below the shoulder reaching may require standing. | |
| Gross manipulation | Gross manipulation involves “seizing, holding, grasping, turning, or otherwise working with the hand(s). Fingers are involved only to the extent that they are an extension of the hand to hold or operate an object or tool, such as hammer” (BLS, 2020, p. 187). It includes handling of large objects. |
| Fine manipulation | Fine manipulation involves “touching, picking, pinching, or otherwise working primarily with fingers rather than with the whole hand or arm” (BLS, 2020, p. 133). It includes writing, typing, or handling small objects (fingering). |
| Foot/leg controls | Refers to the “use of one or both feet or legs to move controls on machinery or equipment. Controls include, but are not limited to, pedals, buttons, levers, and cranks” (BLS, 2020, p. 133). |
| Climbing | “The act of ascending or descending stairs, ramps, ladders, ropes or scaffolding and similar structures using feet, legs, hands, and/or arms” (BLS, 2020, p. 142). |
| Activity | Definition |
|---|---|
| Low work | Low work is a group of activities that includes stooping, crouching, kneeling, crawling, and lying on the ground. |
| From a functional perspective, lying on the ground has more in common with other low work activities in that it includes the need to get up and down from the ground and potentially squirming around to do work while on the ground. These are difficult tasks that are equivalent to the other low work activities. | |
| Vision, Hearing, and Speaking Activities | |
| Near visual acuity | “Clarity of vision at approximately 20 inches or less, as when working with small objects or reading small print” (BLS, 2020, p. 154), including the use of a computer in support of a critical job function, regardless of distance. |
| Far visual acuity | “Clarity of vision at a distance of 20 feet or more, involving the ability to distinguish features of a person or objects at a distance” (BLS, 2020, p. 154). |
| Peripheral vision | “What is seen above, below, to the left or right by the eye while staring straight ahead” (BLS, 2020, p. 154). |
| Hearing | “Ability to hear, understand, and distinguish speech and/or other sounds” (BLS, 2020, p. 149). Includes hearing in-person one-on-one and group or conference communication; telephones and similar devices, such as radios, walkie-talkies, intercoms, and public address systems; and other such sounds as machinery alarms and equipment sounds. Passing a hearing test may be required for certain jobs. |
| Activity | Definition |
|---|---|
| Speaking | “Expressing or exchanging ideas by means of the spoken word to impart oral information to clients or the public and to convey detailed spoken instructions to other workers accurately, loudly, or quickly” (BLS, 2020, p. 149). |
| Mental Activities | |
| Understand, remember, and apply information | The abilities to learn, recall, and use (apply) information (SSA, n.d.-c, n.d.-d). |
| Concentrate, persist, or maintain pace | The abilities to focus attention on work/school activities and stay on task at a sustained rate (SSA, n.d.-c, n.d.-d). |
| Problem solve | “Analyze issues and make decisions that have a moderate to significant level of difficulty (e.g., the full extent of issues may not be readily apparent and requires independent judgment and research or investigation). The defining characteristics of problem solving are that there is no obvious, immediate solution to a problem or issue, and the worker must identify and weigh alternatives to arrive at a solution” (BLS, 2020, p. 99). |
| Interact with others |
The abilities to relate to and work with supervisors, coworkers, the public, teachers, peers, and others—for example,
cooperating with others; asking for help when needed; handling conflicts with others; stating [one’s] point of view; initiating or sustaining conversation; understanding and responding to social cues (physical, verbal, emotional); responding to requests, suggestions, criticism, correction, and challenges; and keeping social interactions free of excessive irritability, sensitivity, argumentativeness, or suspiciousness. (SSA, n.d.-c; see also SSA, n.d.-d) |
| Adapt or manage oneself |
The abilities to “regulate emotions, control behavior, and maintain well-being” in a work or school setting—for example,
responding to demands; adapting to changes; managing [one’s] psychologically based symptoms; distinguishing between acceptable and unacceptable work performance; setting realistic goals; making plans for [oneself] independently of others; maintaining personal hygiene and [appropriate attire]; and being aware of normal hazards and taking appropriate precautions. (SSA, n.d.-c; see also SSA, n.d.-d) |
SOURCES: BLS, 2020; SSA, n.d.-c, n.d.-d.
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Subluxations and dislocations | Patella |
|
|
|
| Shoulder |
|
|
||
| Hip |
|
|
||
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Ankle/subtalar joint |
|
|
||
| Temporomandibular joint (TMJ) |
|
|
|
|
| Rib |
|
|
||
| Other common joints |
|
|
||
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Instability | Cervical |
|
|
|
| Lumbar and sacroiliac |
|
|
|
|
| Costochondritis |
|
|
||
| Hand/finger instability |
|
|
||
| Pain | Joint pain |
|
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Chronic pain syndrome |
|
|
|
|
| Spinal pain (including, but not limited to, instability, muscle spasm, nerve compression, facet joint syndromes) |
|
|
||
| Headache |
|
|
|
|
| Tendon and ligament disorders | Tendon abnormalities |
|
|
|
| Plantar fasciitis |
|
|
||
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Cartilage disorders | Meniscus tears |
|
|
|
| Hip labrum tears, “snapping hip syndrome,” hip impingement |
|
|
||
| Shoulder labrum tears |
|
|
||
| Triangular fibrocartilage complex |
|
|
||
| Myofascial disorders | Muscle spasms/trigger points |
|
|
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| Myofascial restriction |
|
|
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| TMJ myofascial pain |
|
|
||
| Chronic pelvic pain |
|
|
||
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Nerve compression disorders | Thoracic outlet syndrome |
|
|
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| Carpal tunnel |
|
|
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| Cubital tunnel |
|
|
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| Sciatica |
|
|
||
| Morton’s neuroma |
|
|
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| Scoliosis |
|
|
|
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| Joint contractures |
|
|
||
NOTES: CCA = congenital contractural arachnodactyly; CT = computed tomography; EDS = Ehlers-Danlos syndromes; EMG = electromyogram; HDCT = heritable disorder of connective tissue; HSD = hypermobility spectrum disorders; LDS = Loeys-Dietz syndrome; MFS = Marfan syndrome.
a Physical therapy includes, but is not limited to, the following interventions:
- Education about posture, body mechanics, ergonomics, joint protection, trigger point management, pain self-management (pain neuroscience, physiological quieting, biofeedback, self-care), POTS self-care, MCAS self-care
- Neuromuscular reeducation: proprioception, motor control, stabilization, balance; may include forms of movement biofeedback; also includes breathing retraining
- Exercise, including range of motion, strengthening, muscle/fascia stretching, cardiovascular exercise; includes named exercise approaches, such as Pilates, tai chi, and yoga, if instructed by someone knowledgeable about EDS; also includes POTS-specific prescribed exercise
- Recommending, training, and/or fitting for braces, splints, orthotics, assistive devices, taping, compression clothing
- Gait training with or without assistive devices, particularly for lumbar and lower extremity conditions
- Physical modalities should not be the core of clinic management but may be helpful to permit active interventions. Modalities include heat/ice, transcutaneous electric nerve stimulation, with less evidence for ultrasound, laser, infrared, and shock wave. Cervical and lumbar traction are a precaution in hypermobility, so should only be used with caution.
- In addition to physical therapy, manual therapy approaches may be performed by a variety of professionals and include, but are not limited to, massage, soft-tissue mobilization, myofascial release, joint mobilizations (mobilizations are a precaution, and manipulations are contraindicated except by experts in manual therapy for EDS), acupuncture, dry needling, and other named manual therapy approaches (e.g., “Mobilization with Movement,” “Visceral Mobilization,” or “Strain Counterstrain”; many other terms are used).
b Self-administered interventions with guidance from a health care provider include, but are not limited to, the following interventions:
- Posture, joint protection principles, ergonomic modifications
- Exercise (including all types that could be recommended/instructed by a physical therapist, occupational therapist, or other qualified health care provider, including Pilates, tai chi, qigong, some forms of yoga, and breathing exercises)
- Physical modalities, such as ice, heat, transcutaneous electric nerve stimulation (TENS).
- Over-the-counter topicals (e.g., diclofenac cream, lidocaine spray, menthol spray/cream, salicylate, CBD, capsaicin) and oral analgesics (e.g., acetaminophen, ibuprofen).
- Using splints, braces, orthoses, compression clothing, assistive devices, taping, etc.
- Self-management of trigger points through exercise, self-manual therapy, topicals, etc.
- Pain self-management using principles of pain neuroscience, physiological quieting, biofeedback, pacing
c Occupational therapy includes, but is not limited to, the following interventions:
- Adapting of person, tasks, and environment to increase function and decrease pain
- Education about posture, body mechanics, ergonomics, joint protection, trigger point management, pain self-management (pain neuroscience, physiological quieting, biofeedback, self-care)
- Neuromuscular reeducation: proprioception, motor control, stabilization, including breathing retraining and, possibly, forms of movement biofeedback
- Exercise: including range of motion, strengthening, muscle/fascia stretching, cardiovascular exercise
- Recommending, training, fabrication, and/or fitting for braces, splints, assistive devices, taping, compression clothing
- Manual therapy: massage, soft-tissue mobilization, myofascial release, joint mobilizations/manipulations (manipulations and, to a lesser degree, mobilizations are a precaution), dry needling (where allowed), and other named manual therapy approaches (e.g., “Mobilization with Movement,” or “Strain Counterstrain”; many terms are used)
- Physical modalities should not be the core of clinical management, but may be helpful to permit active interventions. These modalities include heat/ice and transcutaneous electroneural stimulation, with less evidence for ultrasound, laser, infrared, and shock wave.
- Cognitive retraining
- Work retraining
SOURCES: Barrett et al., 2021; Bier et al., 2018; Blanpied et al., 2017; Butts et al., 2017; Carpal tunnel syndrome, 2019; Celletti et al., 2021; Clinical guidance to optimize work participation after injury or illness, 2021; Daley et al., 2021; De Baets et al., 2021; Enseki et al., 2014; Erickson et al., 2019; Exercise for knee injury prevention, 2018; Finucane et al., 2020; George et al., 2021; JOSPT infographic, 2021; Kareha et al., 2021; Knee ligament sprain guidelines, 2017; Lin et al., 2020; Logerstedt et al., 2017; Logerstedt et al., 2018; Martin et al., 2021; Minhas, 2021; Oliveira et al., 2018a; Palmer et al., 2021; Physical therapy after an ankle sprain, 2021; Price et al., 2020; Reischl et al., 2020; Reychler et al., 2021; Røe, 2014; Steinberg et al., 2021; van Rossom et al., 2018; Wallis et al., 2021; Willy et al., 2019.
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Cranial disorders | Migraines |
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| Empty sella turcica syndrome |
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| Delayed cognitive development |
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| Craniosynostosis |
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|
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| Intracranial venous stenosis |
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| Eagle syndrome |
|
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|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Intracranial pressure | Intracranial hypertension |
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| Intracranial hypotension |
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| Chiari malformation |
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| Spinal disorders | Atlanto-occipital instability |
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| Atlanto-axial instability |
|
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| Basilar invagination |
|
|
|
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| Spontaneous CSF leak |
|
|
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| Vertebral artery torsion |
|
|
|
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| Myodural bridges |
|
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|
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| Tethered cord syndrome |
|
|
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|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Segmental instability |
|
|
|
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| Segmental kyphosis |
|
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| Scoliosis |
|
|
|
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| Tarlov cysts |
|
|
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| Dural ectasia |
|
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| Instability or malformation of the cervical and thoracic spine |
|
|
|
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| Movement disorders | Dystonia |
|
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| Tremor |
|
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|
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| Chorea |
|
|
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| Myoclonus |
|
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| Tic disorders |
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| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Neuropathies | Compression neuropathy |
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| Overstretch neuropathy |
|
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| Brachial plexopathy |
|
|
|
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| Common peroneal neuralgia |
|
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|
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| Complex regional pain syndrome |
|
|
|
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| Axonal polyneuropathy |
|
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| Small fiber neuropathy |
|
|
|
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| Dysautonomia | POTS |
|
|
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| Hyperadrenergic POTS |
|
|
|
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| Neurocardiogenic syncope |
|
|
|
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| Multiple system atrophy |
|
|
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Pure autonomic failure |
|
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|
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| Autoimmune autonomic ganglionopathy |
|
|
|
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| Thoracic outlet syndrome (TOS) | Neurogenic TOS |
|
|
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| Venous TOS |
|
|
|
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| Arterial TOS |
|
|
|
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| Anterior cutaneous nerve entrapment syndrome |
|
|
|
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| Mitochondrial dysfunction, secondary |
|
|
|
|
NOTE: CSF = cerebrospinal fluid; EDS = Ehlers-Danlos syndrome; HDCT = heritable disorder of connective tissue; hEDS = hypermobile Ehlers-Danlos syndrome; HSD = hypermobility spectrum disorders; LDS = Loeys-Dietz syndrome; MFS = Marfan syndrome.
SOURCES: Bozkurt et al., 2018; Bragée et al., 2020; Carvalho et al., 2020; Castori et al., 2015a; Castori and Voermans, 2014; Cazzato et al., 2016; Collins and Orpin, 2021; Corbett et al., 1982; Donkervoort et al., 2015; Ezzeddine et al., 2005; Fu and Levine, 2015, 2018; Galan and Kousseff, 1995; Grabb et al., 1999; Granata et al., 2013; Halko et al., 1995; Henderson et al., 2017; 2019; Jacome, 1999; Klinge, 2015; Levine et al., 2021; Levine and Rigby, 2018; Martin and Neilson, 2014; Milhorat et al., 2007; Papapetropoulos et al., 1981; Pretorius and Butler, 1983; Puledda et al., 2015; Rozen et al., 2006; Rubinstein and Cohen, 1964; Sadler et al., 2020; Savasta et al., 2011; Schievink et al., 1990; 1996; Schoolman and Kepes, 1967; Song et al., 2020; Toprak Celenay and Ozer Kaya, 2017; Vitaliti et al., 2017; Voermans et al., 2010a.
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments |
|---|---|---|---|
| Ascending aortic aneurysm |
|
|
|
| Descending aortic dissection |
|
|
|
| Ascending aortic dissection |
|
|
|
| Aortic regurgitation |
|
|
|
| Bicuspid aortic valve |
|
|
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| Mitral valve prolapse |
|
|
|
| Arterial tortuosity |
|
|
|
| Arterial rupture |
|
|
|
| Varicose veins |
|
|
|
| Anemia |
|
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments |
|---|---|---|---|
| Excessive bleeding associated with minor trauma, dental procedures, surgical interventions, menstruation, postpartum bleeding, etc. |
|
|
|
NOTE: CBC = complete blood count; CCA = congenital contractural arachnodactyly; CT = computed tomography; EDS = Ehlers-Danlos syndromes; HDCT = heritable disorder of connective tissue; ISTH = International Society on Thrombosis and Haemostasis; LDS = Loeys-Dietz syndrome; MFS = Marfan syndrome; SGS = Shprintzen Goldberg syndrome; vWF = von Willebrand Factor.
SOURCES: Beighton, 1969; Castori et al., 2012; D’Hondt et al., 2018; Drera et al., 2011; Gilliam et al., 2020; Jesudas et al., 2019; Kornhuber et al., 2019; Lind and Wallenburg, 2002; Makatsariya et al., 2020; Murray et al., 2014.
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Inflammatory | Asthma |
|
Objective confirmation of diagnosis
Assessment of control
Asthma phenotype screening
Environmental screening
Exclusionary testing
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Chronic or recurrent sinusitis |
|
If chronic sinusitis:
|
|
|
| Recurrent bronchitis or pneumonia |
|
|
|
|
| Bronchiectasis |
|
|
|
|
| Costochondritis |
|
|
|
|
| Functional | Obstructive sleep apnea |
|
|
|
| Central sleep apnea |
|
|
|
|
| Tracheomalacia |
|
|
|
|
| Reduced inspiratory muscle strength |
|
|
|
|
| Obstructive physiology |
|
|
|
|
| Thoracic Insufficiency Syndrome |
|
|
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Structural, lung | Spontaneous pneumothorax |
|
|
|
| Pulmonary cysts, blebs, and/or bullae |
|
|
|
|
| Hemopneumo-thorax, lung hemorrhage |
|
|
|
|
| Early onset emphysema |
|
|
|
|
| Fibrous nodules |
|
|
|
|
| Structural, musculoskeletal | Diaphragm rupture |
|
|
|
| Cervical spine instability |
|
|
|
|
| Kyphosis or scoliosis |
|
|
|
|
| Pectus excavatum or carinatum |
|
|
|
|
| Rib subluxation |
|
|
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Procedural or postprocedural complications | Increased rates of respiratory failure post–vascular surgery |
|
|
|
| Hemorrhage |
|
|
|
|
NOTE: BHDS = Birt-Hogg-Dubé syndrome; CT = computed tomography; EDS = Ehlers-Danlos syndrome; GERD = gastroesophageal reflux disease; GI = gastrointestinal; HSD = hypermobility spectrum disorder; HDCT = heritable disorder of connective tissue; LDS = Loeys-Dietz syndrome; LPR = laryngopharyngeal reflux; MFS = Marfan syndrome.
SOURCES: Abishek et al., 2019; American Thoracic Society and European Respiratory Society, 2002; Bascom et al., 2021; Bezerra et al., 2014; Birchall et al., 2021; Boone et al., 2019; Camacho et al., 2015; Chohan et al., 2021; Cloutier et al., 2020; Culver et al., 2017; Global Initiative for Asthma, 2021; Graham et al., 2019; Hakim et al., 2021; Halvorsen et al., 2017; Henderson et al., 2017; Henneberger et al., 2011; Holguin et al., 2020; Holland et al., 2014, 2021; Jayarajan et al., 2020; Khatri et al., 2021; Mott et al., 2021; Oliveira et al., 2018b; Qiu et al., 2021; Reychler et al., 2019; Rosen et al., 2018; Rueda et al., 2020; Schoser et al., 2017; Shusterman et al., 2017; Stachler et al., 2018; Tun et al., 2021.
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Mast cell activation disease (MCAD)—single organ |
Skin
|
|
|
|
Airway
|
||||
Gastrointestinal disorders
|
|
|||
Neuropsychiatric
|
|
|
||
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Mast cell activation disease (MCAD)—single organ |
Genitourinary
|
|
|
|
| MCAD—multiorgan disease Mast cell activation syndrome (MCAS) |
|
|
|
|
| Delayed-type hypersensitivity (DTH) Eosinophilic/T2 inflammation |
|
|
|
|
| Primary immunodeficiency (PID)/dysfunction |
|
|
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Autoinflammatory disorders |
|
|
|
|
| DTH: Gastrointestinal disorders |
Hypersensitivity gastroenteritis (see above) |
|
|
|
|
Eosinophilic esophagitis/gastroenteritis |
||||
|
Inflammatory bowel disease (ulcerative colitis, Crohn’s disease) |
|
|
||
| Celiac disease |
|
|
||
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| DTH: Endocrinopathies | Addison’s disease |
|
|
|
|
Thyroiditis (Hashimoto’s disease) |
|
|
||
|
|
|
||
| DTH: Cutaneous disorders | Contact dermatitis |
|
|
|
|
Hereditary angioedema (swelling): skin, oropharynx |
|
|
Acute attacks:
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| DTH: Neurological disorders |
Autoimmune neuropathies/encephalopathies |
|
|
|
|
Chronic immune demyelinating neuropathy |
|
|||
| Multiple sclerosis |
|
|||
|
Postural orthostatic tachycardia syndrome/neuronal mediated hypotension |
|
|
||
|
Small fiber neuropathy |
|
|
||
| DTH: Musculoskeletal and rheumatological disorders |
Arthritides
|
|
|
|
NOTE: ACTH = adrenocorticotropic hormone; CRP = C-reactive protein; CSF = cerebrospinal fluid; EDS = Ehlers-Danlos syndromes; ESR = erythrocyte sedimentation rate; HDCT = heritable disorder of connective tissue; HSCT = hematopoietic stem cell transplantation; HSD = hypermobility spectrum disorder; IPEX = immune dysregulation, polyendocrinopathy, enteropathy, X-linked; RAST = radioallergosorbent test.
SOURCES: Abonia et al., 2013; Arkwright and Gennery, 2011; Cazzato et al., 2016; Cheung and Vadas, 2015; Dang et al., 2019; Hamilton, 2018; Hamilton et al., 2021; Khan, 2013; Leganger et al., 2022; Louisias et al., 2013; Luskin et al., 2021; Lyons et al., 2016; Morgan et al., 2007; Shin et al., 2010; Theoharides et al., 2015; Whitmore and Theoharides, 2011.
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| GastrointestinaI (GI) bleeding |
|
|
|
|
| Visceroptosis |
|
|
|
|
| Intussusception/volvulus |
|
|
|
|
| Diverticulitis |
|
|
|
|
| Organ rupture (e.g., bowel, liver, spleen) |
|
|
|
|
| Median arcuate ligament syndrome |
|
|
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Superior mesenteric artery syndrome |
|
|
|
|
| Eventration of the diaphragm |
|
|
|
|
| Immune-mediated GI disorders | Irritable bowel syndrome |
|
|
|
| Gastroparesis |
|
|
|
|
Inflammatory bowel diseases:
|
|
|
|
|
| Celiac disease |
|
|
|
|
| Eosinophilic gastrointestinal disease |
|
|
|
|
NOTE: CBC = complete blood count; EDS = Ehlers-Danlos syndrome; HDCT = heritable disorder of connective tissue; LDS = Loeys-Dietz syndrome; MFS = Marfan syndrome.
SOURCES: Brooks et al., 2021; Castori et al., 2015b; de Leeuw et al., 2012; Dordoni et al., 2013; Fikree et al., 2017; Frank et al., 2019; Guerrerio et al., 2016; Hassan et al., 2002; Huynh et al., 2019; Inayet et al., 2018; Iwama et al., 1989; Kahn et al., 1988; Kucera and Sullivan, 2017; Laszkowska et al., 2016; Leganger et al., 2016; Lybil and Genie, 2019; MacCarrick et al., 2014; Malyuk et al., 2022; Nelson et al., 2015a; Reinstein et al., 2012; Suster et al., 1984; Yasuda et al., 2013.
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Structural |
|
|
|
|
|
|
|
|
|
| Inflammatory |
Inflammatory dermatoses Atopic dermatitis |
|
|
|
| Urticaria/angioedema |
|
|
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Neuropathic |
Complex regional pain syndrome Reflex sympathetic dystrophy syndrome |
|
|
|
Erythromelalgia
|
|
|
|
|
|
Diaphoresis or hyperhidrosis |
|
|
|
|
NOTE: ANA = antinuclear antibody; BCS = brittle cornea syndrome; EDS = Ehlers-Danlos syndrome; ESR = erythrocyte sedimentation rate; HDCT = heritable disorder of connective tissue; HSD = hypermobility spectrum disorder; LDS = Loeys-Dietz syndrome; MFS=Marfan syndrome.
SOURCES: American Academy of Dermatology Association, 2022; Bechara et al., 2007; Castori, 2012; Catala-Pétavy et al., 2009; Kalava et al., 2013; Malfait et al., 2017; Oaklander and Klein, 2013; Tang et al., 2015.
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Pelvic floor disorders | Stress urinary incontinence |
|
|
|
| Urge urinary incontinence | ||||
| Urinary retention and voiding dysfunction | ||||
| Urinary problems secondary to vascular and neurologic complications |
|
|
||
| Pelvic organ prolapse (bowel, uterus, bladder) |
|
|
|
|
| Vulvodynia and dyspareunia |
|
|
|
|
| Chronic pelvic pain |
|
|
|
|
| Uterine disorders | Menorrhagia |
|
|
|
| Dysmenorrhea |
|
|
||
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Renal abnormalities | Cysts |
|
|
|
| Focal glomerulosclerosis |
|
|
|
|
| Interstitial cystitis |
|
|
|
|
| Pregnancy-related diagnoses | Preterm delivery/premature rupture of membranes |
|
|
|
| Cervical insufficiency |
|
|
|
|
| Aortic root dissection |
|
|
|
|
| Uterine rupture |
|
|
|
|
| Obstetrical hemorrhage |
|
|
|
|
NOTE: CT = computed tomography; EDS = Ehlers-Danlos syndrome; HDCT = heritable disorder of connective tissue; HSD = hypermobility spectrum disorder; LDS = Loeys-Dietz syndrome; MFS = Marfan syndrome.
SOURCES: Bas et al., 2015; Berglund and Björck, 2012; Blagowidow, 2021; Carley and Schaffer, 2000; Carr et al., 1994; Castori et al., 2012; Cauldwell et al., 2019a,b; Chan et al., 2019; Chow et al., 2007; De Martino et al., 2019; De Toma et al., 2000; Demirdas et al., 2017; Donnez, 2011; Drera et al., 2011; Gilliam et al., 2020; Glayzer et al., 2021; Gupta et al., 2010; Henderson et al., 2017; Hentzen et al., 2018; Hernandez and Dietrich, 2020; Hugon-Rodin et al., 2016; Hurst et al., 2014; Jabs and Child, 2016; Jesudas et al., 2019; Kho and Shields, 2020; Kliethermes et al., 2016; Lind and Wallenburg, 2002; Makatsariya et al., 2020; Practice bulletin no. 176: Pelvic organ prolapse, 2017; Ritelli et al., 2013; Rosen et al., 2019; Russo et al., 2018; Sorokin et al., 1994; van de Laar et al., 2011; van de Laar et al., 2012; Wallace et al., 2019.
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Vision | ||||
| Disorders of cornea | Thinning and steepening |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Disorders of conjunctiva |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Disorders of lens/iris |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Disorders of eyelid/face/orbit |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Disorders of optic nerve/brain |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Manifestations | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments | |
|---|---|---|---|---|
| Disorders of retina |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Hearing | ||||
| Disorders of hearing |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Speech | ||||
| Disorders of speech |
|
|
|
|
NOTE: BCS = brittle cornea syndrome; CT= computed tomography; CTA = computed tomography angiography; EDS = Ehlers-Danlos syndrome; HDCT = heritable disorder of connective tissue; HSD = hypermobility spectrum disorder; ICP = intracranial pressure; IOP = intraocular pressure; LDS = Loeys-Dietz syndrome; MFS = Marfan syndrome; MRA = magnetic resonance angiography; MRI = magnetic resonance imaging; MRV = magnetic resonance venography; OCT = optical coherence tomography; UBM = ultrasound biomicroscopy.
SOURCES: ASHA, 2005; Braverman et al., 2020; Gao et al., 2021; Hamberis et al., 2020; Hear.com, n.d.; Islam et al., 2020; Jeon et al., 2022; Kanigowska et al., 2006; NASEM, 2016, p. 82; NORD, 2017a; Perez-Roustit et al., 2019; Rezar-Dreindl et al., 2019; Roeser et al., 2000; Romano et al., 2002; Segev et al., 2006; University of California San Fransico Health, n.d.
| Conditions | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments |
|---|---|---|---|
| Cognitive dysfunction/mild cognitive impairment |
|
Structured interviews:
Performance-based measures:
|
|
| Depression |
|
Structured interviews:
Self-reported measures:
|
|
| Anxiety disorders |
|
Structured interviews:
Self-reported measures:
|
|
| Conditions | HDCTs (Selected) | Common Diagnostic Techniques | Potential Treatments |
|---|---|---|---|
| Intellectual disability |
|
Performance-based measures:
|
|
| Personality disorder |
|
Self-reported measures:
|
|
| Sleep disorders |
|
Structured interviews:
Self-reported measures:
|
|
| Eating disorders |
|
Structured interviews:
Self-reported measures:
|
|
| Attention-deficit/hyperactivity disorder (ADHD) |
|
Structured interviews:
Self-reported measures:
|
|
NOTE: ADL = activities of daily living; EDS = Ehlers-Danlos syndrome; HDCT = heritable disorder of connective tissue; hEDS = hypermobile EDS; HSD = hypermobility spectrum disorder; MFS = Marfan syndrome; SGS = Shprintzen-Goldberg syndrome.
SOURCES: Arnold et al., 2015; Baeza-Velasco et al., 2016, 2017, 2018, 2021, 2022a,b; Becker et al., 2021; Berglund et al., 2015; Bulbena-Cabré et al., 2021; Cederlöf et al., 2016; Cicerone et al., 2019; Doğan et al., 2011; Domany et al., 2018; Eccles et al., 2014; Greally, 2020; Hershenfeld et al., 2016; Hofman et al., 1988; Huang et al., 2020; Kandola and Stubbs, 2020; Kandola et al., 2018; Lambez et al., 2020; Langhinrichsen-Rohling et al., 2021; Lannoo et al., 1996; Moss et al., 2018; Nijs et al., 2018; NORD, 2017b; Oppizzi and Umberger, 2018; Pasquini et al., 2014; Reisberg et al., 1982; Ross et al., 2013; Shiari et al., 2013; Smith et al., 2013; Tsui et al., 2017; Wasim et al., 2019; Wells et al., 2020; Zhang and Yuan, 2019.
ANNEX TABLE 5-13
Global Functioning Associated with Heritable Disorders of Connective Tissue
| Domain | Potential Reasons for Limitation or Symptom | Selected Assessments | Selected Assistive Technologies and Relevant Accommodations |
|---|---|---|---|
| Full-body functioning (physical) |
|
Performance-based measures:
Self-reported measures:
|
|
| Domain | Potential Reasons for Limitation or Symptom | Selected Assessments | Selected Assistive Technologies and Relevant Accommodations |
|---|---|---|---|
| Work-related functioning, activities of daily living (ADLs), and instrumental activities of daily living (IADLs) |
|
Performance-based measures:
Observation and interview-based measures:
|
|
|
Self-reported measures:
Caregiver-reported measures:
|
|||
| Domain | Potential Reasons for Limitation or Symptom | Selected Assessments | Selected Assistive Technologies and Relevant Accommodations |
|---|---|---|---|
| Pain |
|
Self-reported measures:
|
|
| Fatigue |
|
Performance-based measures:
Self-reported measures:
|
|
* Multidimensional assessment: Balance, coordination, dexterity, functional mobility, gait, strength, upper-extremity, function, vestibular.
| Activity | Potential Reasons for Activity Limitation | Selected Functional Assessments | Selected Assistive Technologies and Reasonable Accommodations |
|---|---|---|---|
| Sitting Note: especially prolonged sitting |
|
Physical performance measures:
Self-reported outcome measures:
|
|
| Standing Note: especially prolonged standing, but intermittent standing and ability to get to standing may also be affected; using assistive devices can be very stressful to upper-extremity (UE) joints |
|
Physical performance measures:
Self-reported outcome measures:
|
|
| Activity | Potential Reasons for Activity Limitation | Selected Functional Assessments | Selected Assistive Technologies and Reasonable Accommodations |
|---|---|---|---|
| Walking Note: may be impaired for long or short distances, over uneven ground or different surfaces; using assistive devices can be very stressful to UE joints |
|
Physical performance measures:
Self-reported outcome measures:
|
|
| Strenuous physical activity Note: potentially includes all other activities in this table, plus running and impact activities |
|
Physical performance measures:
|
|
| Lifting from floor to waist or overhead |
|
Physical performance measures:
Self-reported outcome measures:
|
|
| Activity | Potential Reasons for Activity Limitation | Selected Functional Assessments | Selected Assistive Technologies and Reasonable Accommodations |
|---|---|---|---|
| Carrying Note: usually requires ability to stand, lift, and walk |
|
Physical performance measures:
Self-reported outcome measures:
|
|
| Pushing or pulling Note: includes UE and LE; for UE, usually requires ability to stand and walk (or move wheelchair) with at least one hand free for pushing/pulling |
|
Physical performance measures:
Self-reported outcome measures:
|
|
| Reaching Note: may require standing |
|
Physical performance measures:
Self-reported outcome measures:
|
|
| Reaching overhead Note: requires neck extension; may require standing |
|
Physical performance measures:
|
|
| Reaching at or below the shoulder Note: may require standing |
|
Physical performance measures:
Self-reported outcome measures:
|
|
| Activity | Potential Reasons for Activity Limitation | Selected Functional Assessments | Selected Assistive Technologies and Reasonable Accommodations |
|---|---|---|---|
| Gross manipulation Note: requires ability to sit and/or stand |
|
Physical performance measures:
Self-reported outcome measures:
|
|
| Fine manipulation |
|
Physical performance measures:
Self-reported outcome measures:
|
|
| Foot/leg controls |
|
Physical performance measures:
Self-reported outcome measures:
|
|
| Climbing Note: may include stairs, ramps, ladders, scaffolding, ropes, etc. Normal ambulation devices might not be usable for climbing. |
|
Physical performance measures:
Self-reported outcome measures:
|
|
| Activity | Potential Reasons for Activity Limitation | Selected Functional Assessments | Selected Assistive Technologies and Reasonable Accommodations |
|---|---|---|---|
| Low work, including stooping, crouching, kneeling, crawling or lying on the ground Note: includes need to get up and down from the ground |
|
Physical performance measures:
Self-reported outcome measures:
|
|
NOTE: KOOS = Knee Injury and Osteoarthritis Outcome Score; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.
| Activity | Potential Reasons for Activity Limitation | Selected Functional Assessments | Selected Assistive Technologies and Reasonable Accommodations |
|---|---|---|---|
| Near visual acuity |
|
|
|
| Distance (far) visual acuity |
|
|
|
| Binocular function |
|
|
|
| Activity | Potential Reasons for Activity Limitation | Selected Functional Assessments | Selected Assistive Technologies and Reasonable Accommodations |
|---|---|---|---|
| Peripheral vision |
|
|
|
| Hearing |
|
Performance-based measures:
Self-reported outcome measures:
|
|
| Speaking |
|
|
|
NOTE: ASHA = American Speech-Language-Hearing Association; EDS = Ehlers-Danlos syndrome.
SOURCES: Giguère et al., 2008; Laroche et al., 2003; McBride et al., 1994; Smits et al., 2004; Watson et al., 2012; Yueh et al., 2003.
| Activity | Potential Reasons for Activity Limitation | Selected Functional Assessments | Selected Assistive Technologies and Reasonable Accommodations |
|---|---|---|---|
| Understand, remember, and apply information |
|
Intellectual abilities and general cognition
|
|
|
Executive functioning
Attention and working memory
Self-reported measures:
|
|||
| Activity | Potential Reasons for Activity Limitation | Selected Functional Assessments | Selected Assistive Technologies and Reasonable Accommodations |
|---|---|---|---|
| Problem solve |
|
Intellectual abilities and general cognition
Executive functioning
Self-reported measures:
|
|
| Concentrate, persist, or maintain pace |
|
Attention and working memory
Processing speed
Self-reported measures:
|
|
| Activity | Potential Reasons for Activity Limitation | Selected Functional Assessments | Selected Assistive Technologies and Reasonable Accommodations |
|---|---|---|---|
| Interact with others |
|
Adaptability/personal interactions Self-reported measures:
Language
|
|
| Adapt or manage oneself |
|
Adaptive functioning
Adaptability/personal interactions
Attention and working memory
Processing speed
Executive functioning
Self-reported measures:
|
|
NOTE: ADHD = attention deficit hyperactivity disorder.
| Listings* | Notes |
|---|---|
| 1.15 Disorders of the skeletal spine resulting in compromise of a nerve root(s) | Standard imaging may not clearly demonstrate abnormalities. Flexion and extension imaging, or magnetic resonance imaging (upright, if tolerated) may be needed. |
| 1.16 Lumbar spinal stenosis resulting in compromise of the cauda equine | Standard imaging might not detect abnormalities. Specialized imaging such as flexion or extension imaging may be needed. Some individuals may be unable to use mobility devices due to upper-extremity impairments. |
| 1.17 Reconstructive surgery or surgical arthrodesis of a major weight-bearing joint | Individuals with HDCTs are more likely to have a poor outcome with major surgery, especially if the HCDT was not previously recognized or taken into account in performing surgery and after-care. Wound healing is slow in many HDCTs and wound dehiscence may occur despite excellent surgical and postoperative care. Some individuals may be unable to use mobility devices due to upper-extremity impairments. Patients are sometimes unable to fully engage in postoperative therapy because of associated problems such as fatigue, orthostatic intolerance, mast cell activation disease, depression, brain fog, gastrointestinal disorders, or other musculoskeletal issues. Surgical outcomes may therefore be compromised. |
| 1.18 Abnormality of a major joint(s) in any extremity | Frequent episodes of subluxation or dislocation strongly impacting function often influence how consistent people can be in performing work activities. For example, if a person’s hip dislocates, they will be unable to stand or walk. Individuals prone to dislocations may be afraid to perform certain activities or even to leave their homes for fear of causing a dislocation. Physical examination and standard imaging might not identify subluxations that only occur with movement or weight bearing. Specific imaging such as dynamic imaging, imaging at end-range, or visualization of soft-tissue damage may be needed. Patients with significant upper-extremity involvement may not be candidates for assistive technology to aid mobility. Consequently, the patient might not have been given a mobility device because he/she would not have been able to effectively use it. |
| Listings* | Notes |
|---|---|
| 1.21 Soft-tissue injury or abnormality under continuing surgical management | Soft-tissue injuries/pain are very common. Sometimes a single body part is severely involved, but it is also common that there may be many body parts that combine to create severe functional limitations. For example, involvement of bilateral upper-extremity involvement in addition to bilateral lower-extremity involvement may limit capacity to use mobility devices. For example, using a wheelchair may aggravate hand instability and pain, thus incapacitating the hands as well. Surgery is often less successful and more often avoided in patients with than in those without hypermobility. Therefore, the requirement of past surgery is less likely to be met even though a patient may have equally severe functional limitations due to soft-tissue problems. Patients are sometimes unable to fully engage in therapy because of associated problems such as fatigue, depression, brain fog, gastrointestinal disorders, or other musculoskeletal issues. |
| 2.02 Loss of central visual acuity (meeting the specified criteria) | |
| 2.03 Contraction of the visual field in the better eye (meeting the specified criteria) | |
| 2.04 Loss of visual efficiency, or visual impairment, in the better eye (meeting the specified criteria) | |
| 2.07 Disturbance of labyrinthine-vestibular function (including Ménière’s disease), characterized by a history of frequent attacks of balance disturbance, tinnitus, and progressive loss of hearing | Might meet vestibular criteria but hearing criteria may not be applicable. |
| 3.03 Asthma | |
| 3.07 Bronchiectasis | |
| 3.14 Respiratory failure | |
| 4.10 Aneurysm of aorta or major branches | |
| 5.08 Weight loss due to any digestive disorder (meeting the specified criteria) | |
| Listings* | Notes |
|---|---|
| 11.08 Spinal cord disorders | |
| 12.04 Depressive, bipolar, and related disorders | |
| 12.06 Anxiety and obsessive-compulsive disorders | |
| 14.09 Inflammatory arthritis | |
* SSA, n.d.-b, provides the criteria for each of the listings included here.
