Hypermobile Ehlers-Danlos Syndrome

Excerpt

Clinical characteristics: Hypermobile Ehlers-Danlos syndrome (hEDS) is characterized by generalized joint hypermobility, joint instability, pain, soft and hyperextensible skin with atrophic scars and easy bruising, dental crowding, abdominal hernias, pelvic organ prolapse, marfanoid body habitus, mitral valve prolapse, and aortic root dilatation. Subluxations, dislocations, and soft tissue injury are common; they may occur spontaneously or with minimal trauma and can be acutely painful. Degenerative joint and chronic soft tissue disorders may arise due to repeated injury. Chronic pain, distinct from that associated with acute injury, is common and often neuropathic in nature. Chronic fatigue, functional bowel disorders, cardiovascular autonomic dysfunction, swallow and phonation disorders, sleep disorders including apnea, migraine, entrapment and peripheral neuropathies, inflammation from mast cell activation disorders, anxiety disorders, and urogynecologic disorders are common. Mitral valve prolapse and aortic root dilatation, when present, are typically of a mild degree with no increased risk of cardiac complications.

Diagnosis/testing: The diagnosis of hEDS is established in an adult proband based on 2017 international clinical diagnostic criteria. Currently, no underlying genetic, epigenetic, or metabolomic etiology has been identified for hEDS.

Management: Treatment of manifestations: Tailored treatment with exercise to increase core and extremity muscle strength and tone, proprioception, and joint stability; braces and splints to improve alignment and control; occupational therapy for assistive devices (e.g., wide-grip writing utensils, home and work ergonomics); physical therapy for assistive devices (e.g., wheelchair or scooter, suitable mattress, soft neck collar); pain management tailored to cause and symptoms; platelet disorders may respond to tranexamic or mefenamic acid; nutrition advice for micronutrient deficiencies; gastritis, gastroparesis, and gastroesophageal reflux disease may require intensive pharmacotherapy; therapies for other gastrointestinal, cardiovascular, ocular, neurologic, and urogynecologic manifestations; orthodontic, maxillofacial, and ENT management for narrow palate, crowded teeth, temporomandibular joint laxity and dysfunction, and disorders of swallow and phonation; standard treatment of periodontal disease; avoidance of triggers for mast cell activation disorder and pharmacotherapy or monoclonal biologic therapy as needed; counseling and pharmacotherapy for neurobehavioral and psychiatric manifestations.

Surveillance: Assess for joint manifestations, pain, disability, bleeding issues, functional bowel disorders, autonomic dysfunction, oral health needs, phonation and respiratory issues, sleep issues, vision issues, headaches and other neurologic manifestations, inflammatory disease, neurobehavioral and psychiatric manifestations, and urogynecologic manifestations annually or at each visit. Dual-energy x-ray absorptiometry in those with height loss greater than one inch, atypical/low trauma fractures, or radiographs suggestive of osteopenia. Follow-up echocardiography in those with aortic root dilatation.

Agents/circumstances to avoid: High-impact activity may increase the risk of acute subluxation/dislocation and acute and chronic pain. Chiropractic adjustment and yoga are not contraindicated but like all other physical treatments must be performed in ways that avoid iatrogenic subluxations or dislocations. Autonomic concerns, gastrointestinal disorders, and intolerances may preclude use of medications or their excipients (e.g., common analgesics in someone with slow gastrointestinal transit, vasodilator in a person with orthostatic intolerance).

Pregnancy management: Preconceptual (e.g., musculoskeletal health and medication use), antenatal (e.g., joint instability, pelvic strength, hernias, and pain management), intrapartum (e.g., birth choices, mobility in labor, anesthesia), and postpartum (e.g., wound healing, pelvic health, newborn/infant care) issues should all be addressed.

Genetic counseling: Hypermobile EDS is inherited in an autosomal dominant manner with variable expression of signs and variable severity of symptoms among affected family members. Most individuals diagnosed with hEDS have an affected parent, although a detailed history and examination of the parents is often necessary to recognize that a parent has a current or prior history of joint laxity, easy bruising, and skin manifestations despite the absence of serious complications. Each child of an individual with hEDS has a 50% chance of inheriting hEDS. Because the gene(s) and pathogenic variant(s) responsible for hEDS have not been identified, prenatal and preimplantation genetic testing are not possible.