Classic Ehlers-Danlos Syndrome

Excerpt

Clinical characteristics: Classic Ehlers-Danlos syndrome (cEDS) is a heritable connective tissue disorder characterized by skin hyperextensibility, atrophic scarring, and generalized joint hypermobility (GJH). The skin is soft, velvety, or doughy to the touch. In addition, the skin is hyperextensible, meaning that it extends easily and snaps back after release. The skin is fragile, as manifested by splitting of the dermis following relatively minor trauma, especially over pressure points (knees, elbows) and areas prone to trauma (shins, forehead, chin). Wound healing is poor, and stretching, thinning, and pigmentation of scars is characteristic, leading to the presence of atrophic and/or hemosiderotic scars. Easy bruising is also a hallmark of cEDS. GJH is present in most but not all affected individuals, evidenced by the presence of a Beighton score of five or greater, either on examination or historically. Joint instability complications may comprise sprains and dislocations/subluxations. Mild muscle hypotonia with delayed motor development, fatigue and muscle cramps, and some skeletal morphologic alterations (scoliosis, pectus deformities, genus/hallux valgus, pes planus) are regularly observed. While aortic root dilatation and mitral valve prolapse are seen in cEDS, they are rarely clinically significant. Arterial aneurysm and rupture have been reported in a few individuals with cEDS.

Diagnosis/testing: The diagnosis of cEDS is established in a proband with characteristic clinical features and a heterozygous pathogenic variant in COL1A1, COL5A1, or COL5A2 identified by molecular genetic testing.

Management: Treatment of manifestations: Dermal wounds are closed without tension, preferably in two layers. For other wounds, deep stitches are applied generously; cutaneous stitches are left in place twice as long as usual; and the borders of adjacent skin are carefully taped to prevent stretching of the scar. Young children with skin fragility can wear pads or bandages over the forehead, knees, and shins to avoid skin tears. Older children can wear soccer pads or ski stockings with shin padding during activities. Braces as needed to improve joint stability; referral to orthopedist, rheumatologist, or physical therapist and occupational therapist as needed. Mobility devices as needed. Adjust sleep surface as needed to improve sleep quality and decrease pain. Those with hypotonia, joint instability, and chronic pain may need to adapt lifestyles accordingly. Anti-inflammatory drugs may alleviate joint pain. Children with hypotonia and delayed motor development benefit from physiotherapy. Non-weight-bearing exercise promotes muscle strength and coordination. Ascorbic acid (vitamin C) may reduce bruising. DDAVP^® (desmopressin) may be useful to normalize bleeding time. Cardiovascular manifestations are treated in a standard manner.

Surveillance: Assess for skin fragility, joint instability, occupational and physical therapy needs, mobility issues, and pain at each visit or as needed. Evaluation for hypotonia and motor development at each visit in infants and children. Assess for easy bruising and/or prolonged bleeding at each visit. Evaluation of clotting factors if severe easy bruising is present. Yearly echocardiogram when aortic dilatation and/or mitral valve prolapse are present.

Agents/circumstances to avoid: Sports with heavy joint strain.

Genetic counseling: Classic EDS is inherited in an autosomal dominant manner. Approximately 50% of individuals diagnosed with cEDS have an affected parent; approximately 50% of individuals diagnosed with cEDS have the disorder as the result of a de novo pathogenic variant. Each child of an individual with cEDS has a 50% chance of inheriting the pathogenic variant. Once the cEDS-related pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.