Classic Ehlers-Danlos Syndrome

Excerpt

Clinical characteristics: Classic Ehlers-Danlos syndrome (cEDS) is a connective tissue disorder characterized by skin hyperextensibility, atrophic scarring, and generalized joint hypermobility (GJH). The skin is soft and doughy to the touch, and hyperextensible, extending easily and snapping back after release (unlike lax, redundant skin, as in cutis laxa). 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 of scars after apparently successful primary wound healing is characteristic. Complications of joint hypermobility, such as dislocations of the shoulder, patella, digits, hip, radius, and clavicle, usually resolve spontaneously or are easily managed by the affected individual. Other features include hypotonia with delayed motor development, fatigue and muscle cramps, and easy bruising. Mitral valve prolapse can occur infrequently, but tends to be of little clinical consequence. Aortic root dilatation has been reported, appears to be more common in young individuals, and rarely progresses.

Diagnosis/testing: The diagnosis of cEDS is established in a proband with the minimal clinical diagnostic criteria (skin hyperextensibility and atrophic scarring and either GJH or ≥3 minor clinical criteria) and identification on molecular genetic testing of a heterozygous pathogenic variant in COL5A1, COL5A2, or (less commonly) COL1A1.

Management: Treatment of manifestations: Children with hypotonia and delayed motor development benefit from physiotherapy. Non-weight-bearing exercise promotes muscle strength and coordination. Anti-inflammatory drugs may alleviate joint pain. Those with hypotonia, joint instability, and chronic pain may need to adapt lifestyles accordingly. 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. DDAVP^® (deamino-delta-D-arginine vasopressin) may be useful to normalize bleeding time. Cardiovascular problems are treated in a standard manner.

Prevention of primary manifestations: 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. Ascorbic acid (vitamin C) may reduce bruising.

Surveillance: Yearly echocardiogram when aortic dilatation and/or mitral valve prolapse are present.

Agents/circumstances to avoid: Sports with heavy joint strain; acetylsalicylate (aspirin).

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