Skip to main content

Currently Skimming:

4 Ehlers-Danlos Syndromes and Hypermobility Spectrum Disorders
Pages 73-124

The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.


From page 73...
... , although they do not meet the diagnostic criteria for EDS. This chapter describes the history, diagnosis, and characteristics of EDS/HSD, and reviews their treatment, management, and selected associated physical and mental secondary impairments, many of which can limit activities and restrict participation of affected individuals in work and school.
From page 74...
... McKusick's first edition of Heritable Disorders of Connective Tissue (1956) chronicled fewer than 100 reports in the literature; this number had risen to 300 by 1966, when the third edition was published.
From page 75...
... c.3227C>T, p.(Arg1093Cys) 5 Hypermobile EDS hEDS AD Unknown Unknown 6 Arthrochalasia EDS aEDS AD COL1A1, COL1A2 Type I collagen 7 Dermatosparaxis dEDS AR ADAMTS2 ADAMTS-2 EDS 8 Kyphoscoliotic EDS kEDS AR PLOD1 LH1 FKBP14 FKBP22 9 Brittle Cornea BCS AR ZNF469 ZNF469 syndrome continued
From page 76...
... NOTE: AD, autosomal dominant; AR, autosomal recessive, IP, inheritance pattern; NMD, nonsense-mediated mRNA decay. them, the International Consortium on the Ehlers-Danlos Syndromes & Hypermobility Spectrum Disorders convened in 2016 to refine the diagnostic criteria for hEDS.
From page 77...
... . DIAGNOSIS OF EHLERS-DANLOS SYNDROMES AND HYPERMOBILITY SPECTRUM DISORDERS Each type of EDS, as well as HSD, has its own set of specific diagnostic criteria (see Annex Table 4-1)
From page 78...
... The clinical diagnostic criteria for 12 other types of EDS are provided on the Ehlers-Danlos Society website,1 but because of the overlap of symptoms among many types of EDS and HSD, definitive diagnosis includes confirmation through genetic testing of those types for which the responsible genes have been identified. The classical type (cEDS)
From page 79...
... Problems in the immune system, for example, such as mast cell activation disease (MCAD) , can manifest as symptoms in other body systems, such as gastrointestinal disorders, respiratory difficulties, nonmigraine headaches, and cognitive dysfunction or impairment, sometimes referred to as "brain fog" (Maitland, 2020)
From page 80...
... The question of whether the symptoms commonly associated with a variety of mental disorders (e.g., anxiety disorders, eating disorders, attentiondeficit/hyperactivity disorder) are manifestations of a physical disorder (e.g., dysautonomia)
From page 81...
... . CHARACTERISTICS OF EHLERS-DANLOS SYNDROMES AND HYPERMOBILITY SPECTRUM DISORDERS Clinical Picture The natural history of EDS/HSD is variable.
From page 82...
... and mental health of children and adolescents aged 4–18 with a variety of HDCTs -- MFS, LDS, hEDS, and other EDS types -- through child- and parent-reported questionnaires (Warnink-Kavelaars, et al., 2022)
From page 83...
... . Rarer EDS types include vEDS, with an estimated prevalence of 1/50,000 (Byers, 2019)
From page 84...
... A recent estimate of the prevalence of EDS/HSD derives from a national electronic cohort study and nested case control study conducted in Wales, United Kingdom. To derive this estimate, the researchers identified persons who were assigned a coded diagnosis of EDS/HSD or joint hypermobility syndrome (an older diagnostic term that includes both HSD and hEDS)
From page 85...
... . Notably, the pathophysiologic relationship between EDS/HSD and many of these manifestations and comorbid conditions is unclear, and the evidence linking them is primarily associative; many are also common in chronic conditions that are not characterized by connective tissue dysfunction.
From page 86...
... . In addition, EDS/HSD patients are at increased risk of craniocervical and other spinal instability and such central nervous system pathologies as Chiari 1 malformation, intracranial hypertension, tethered cord syndrome, and syringomyelia (Henderson et al., 2017; Klinge et al., 2021, 2022)
From page 87...
... . Depression is common among individuals with other chronic conditions, including pain, and dysautonomias can cause symptoms commonly associated with anxiety.
From page 88...
... . More recent clinical guidance was published in the December 2021 issue of the American Journal of Medical Genetics (Hakim et al., 2021)
From page 89...
... Anyone newly diagnosed with vEDS or some other rare EDS type that is considered to pose a high risk of significant cardiovascular involvement should be referred to a clinical center with experience and expertise in EDS management (Byers et al., 2017)
From page 90...
... Scoliosis may be diagnosed in both children and adults, and clinically significant scoliosis may necessitate bracing or surgical intervention, especially in patients with kEDS but also in those with the cEDS, hEDS/HSD, and arthrochalasia EDS types. Experts in spine care should be involved in the care of EDS/ HSD patients experiencing neck pain; headaches; migraines; or signs and symptoms suggestive of Chiari I malformation, intracranial hypertension, craniocervical or atlantoaxial instability, tethered cord, syringomyelia, dystonias, or Tarlov cysts (Henderson et al., 2017)
From page 91...
... . Immunologic involvement, particularly in patients with recurrent infections or those with symptoms of mast cell activation, requires consultation with a provider with expertise in allergy and immunology.
From page 92...
... Determining the presence and severity of patient-specific and EDS/HSD type–specific manifestations, such as bleeding, poor wound healing, cardiovascular involvement, or increased risk of joint subluxation or dislocation and cervical spine injury, is crucial during preoperative consultation. Tissue fragility associated with HDCTs motivated a recent assessment of surgical risk associated with EDS/HSD (and Marfan syndrome)
From page 93...
... . Mast cells play a role in wound healing (Komi et al., 2020)
From page 94...
... Perform skin closure in is not severe in JHS/EDS-HT, and two layers (cutaneous and delayed wound healing with Rosenberg, subcutaneous) without excessive consequent suture widening, 2012; tension.
From page 95...
... . PROGNOSIS The prognosis and clinical course of EDS/HSD depend on individual patient factors (e.g., personal factors in the International Classification of Functioning, Disability and Health [ICF]
From page 96...
... Longitudinal studies of individuals with different types of EDS/HSD would increase understanding of the clinical course of the disorders; their effects on functioning; and potentially the impact of interventions, including reasonable accommodations, on participation in work and school. EMERGING TREATMENTS Emerging treatments or interventions for EDS/HSD are limited; clinical trials evaluating the efficacy of various treatments, aimed not only at the underlying disease but also at the specific disease-associated manifestations, are generally lacking.
From page 97...
... Hypermobility spectrum disorders (HSD) are also multisystem connective tissue disorders that are clinically similar to hypermobile EDS (hEDS)
From page 98...
... 4-3. Management of EDS/HSD requires a multidisciplinary approach and involves early diagnosis of the multisystem findings, treatment of associated physical and mental secondary impairments, and mea sures to reduce or prevent problems that may present over time.
From page 99...
... American Journal of Medical Genetics Part C: Seminars in Medical Genetics 187(4)
From page 100...
... American Journal of Medical Genetics Part C: Seminars in Medical Genetics 175(1)
From page 101...
... 2021. Updates on the psychological and psychiatric aspects of the Ehlers-Danlos syndromes and hyper mobility spectrum disorders. American Journal of Medical Genetics Part C: Seminars in Medical Genetics 187(4)
From page 102...
... American Journal of Medical Genetics Part C: Seminars in Medical Genetics 169C(1)
From page 103...
... 2005. Generalized joint hypermobility and temporomandibular disorders: Inherited connective tissue disease as a model with maximum expression.
From page 104...
... American Journal of Medical Genetics Part C: Seminars in Medical Genetics 175(1)
From page 105...
... American Journal of Medical Genetics Part C: Seminars in Medical Genetics 175(1)
From page 106...
... American Journal of Medical Genetics Part C: Seminars in Medical Genetics 169C(1)
From page 107...
... American Journal of Medical Genetics Part C: Seminars in Medical Genetics 187(4)
From page 108...
... American Journal of Medical Genetics.
From page 109...
... American Journal of Human Genetics 92(6)
From page 110...
... American Journal of Medical Genetics Part C: Seminars in Medical Genetics 187(4)
From page 111...
... In Connective tissue and its heritable disorders: Molecular, genetic, and medical aspects. 2nd ed., edited by B
From page 112...
... 2022. Heritable connective tissue disorders in childhood: Decreased health-related quality of life and mental health. American Journal of Medical Genetics.
From page 113...
... American Journal of Medical Genetics Part C: Seminars in Medical Genetics 187(4)
From page 114...
... Classical EDS The classical type of EDS is an autosomal-dominant connective Diagnostic criteria tissue disorder associated with skin hyperextensibility, articular International EDS Consortium hypermobility, and tissue fragility with peculiar "cigarette- Laboratory genetic (mutation) paper" scars.
From page 115...
... Classical-like EDS type 2 Classical-like EDS type 2 is an autosomal-recessive disorder that Diagnostic criteria falls in the EDS spectrum, associated with joint hypermobility, Similar to classical form of EDS but skin laxity, delayed wound healing, abnormal scarring, and aortic with autosomal-recessive inheritance dilation. Clinical findings include joint laxity with dislocations, Laboratory genetic (mutation)
From page 116...
... The vascular form of EDS is an autosomal-dominant disorder Diagnostic criteria defined by the major complications of arterial and bowel rupture, Suspected if patient, particularly and uterine rupture during pregnancy. Clinical features include younger than age 40, presents short stature; thin lips; lobeless ears; keratoconus; pinched- with one of the following: arterial appearing, thin nose; periodontal disease and early loss of aneurysms, dissection, or rupture; teeth; mitral valve prolapse; intracranial aneurysms; spontaneous intestinal rupture; uterine rupture pneumothorax and hemoptysis; inguinal hernias; spontaneous during pregnancy; family history of rupture of bowel; uterine rupture during pregnancy; uterine and vEDS bladder prolapse; joint laxity of the distal phalanges with acro- Laboratory genetic (mutation)
From page 117...
... include mild to moderate short stature; midface hypoplasia; testing severe joint dislocations with recurrent joint subluxations; early- COL1A1 onset osteoarthritis; osteopenia with increased risk for fractures; COL1A2 kyphoscoliosis and scoliosis; congenital hip dislocations; thin, hyperextensible, atrophic scars; hypotonia with gross-motor developmental delay. Dermatosparaxis EDS Dermatosparaxis EDS is an autosomal-recessive disorder of Diagnostic criteria connective tissue resulting from deficiency of procollagen Autosomal-recessive inheritance peptidase.
From page 118...
... include rupture of medium-size arteries, cardiac failure, decreased testing pulmonary function, recurrent pneumonias, and respiratory PLOD1 insufficiency secondary to chest deformity. Other laboratory findings Increased ratio of deoxypyridinoline to pyridinoline crosslinks in urine measured by high-performance liquid chromatography  Kyphoscoliotic EDS type 2 Kyphoscoliotic EDS type 2 is an autosomal-recessive disorder Diagnostic criteria caused by mutations in the gene encoding FKBP14.
From page 119...
... Laboratory genetic (mutation) testing ZFN469 Other laboratory findings Normal lysyl hydroxylase activity  Normal dermal hydroxylysine content  Brittle cornea syndrome type 2 Brittle cornea syndrome type 2, one of the EDS, is an autosomal- Diagnostic criteria recessive disorder due to mutations in the gene PDRM5.
From page 120...
... Laboratory genetic (mutation) testing B3GALT7 Other laboratory findings Galactosyltransferase I deficiency in fibroblasts  Spondylodysplastic EDS type 2 Spondylodysplastic EDS type 2 is an autosomal-recessive disorder Diagnostic criteria caused by mutations in the B3GALT6 gene.
From page 121...
... ratio approximately 1 (nl LP/HP: 0.2 + 0.03) Musculocontractural EDS type 1 Musculocontractural EDS type 1 is an autosomal-recessive disorder Diagnostic criteria caused by mutations in the CHST14 gene.
From page 122...
... Characteristic Clinical findings findings include hypotonic facies with prominent and abnormally Laboratory genetic (mutation) shaped ears, hypertelorism, blue sclera, mitral valve prolapse testing and regurgitation, mixomatous degeneration of mitral valve, DSE eventration of abdominal wall after surgery, hernia, uterine and Other laboratory findings bladder prolapse in females, arachnodactyly, camptodactyly, talipes Adulthood, abnormal muscle fiber equinovarus, delayed wound healing with atrophic scars, recurrent pattern in histology large subcutaneous hematomas, postecchymotic calcifications, generalized muscle weakness, pain, and occasional cerebral atrophy.
From page 123...
... bruisability, pretibial hyperpigmentation, and pretibial plaques. testing C1R Other laboratory findings Electron microscopy: Abnormally enlarged endoplasmic reticulum cisterna  Abnormal variation in collagen fibril diameter  Periodontal EDS type 2 Periodontal EDS type 2 is an autosomal-dominant disorder caused Diagnostic criteria by heterozygous mutation in the C1S gene.
From page 124...
... G-HSD can be also associated with extra-articular complications that include anxiety disorders, orthostatic tachycardia, a variety of functional gastrointestinal disorders, and pelvic and bladder dysfunction often similar to what is seen in hEDS. NOTE: HDCT = heritable disorder of connective tissue and disability.


This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More information on Chapter Skim is available.