Musculocontractural Ehlers-Danlos Syndrome

Musculocontractural Ehlers-Danlos syndrome is a rare autosomal recessive disorder of dermatan sulphate biosynthesis, caused by CHST14 (type 1) or DSE (type 2) variants. It combines congenital contractures, distinctive facial features and progressive skin, joint and visceral fragility.

Pathophysiology. Loss of dermatan 4-O-sulphotransferase 1 (CHST14) or dermatan sulphate epimerase (DSE) replaces dermatan sulphate with chondroitin sulphate in decorin and other proteoglycans. Collagen fibril assembly is disrupted, causing tissue fragility.

It is very rare, found in many ethnic groups, and presents at birth with contractures and dysmorphism.

Complications accumulate with age and include haematomas, bowel perforation and cardiac valve disease.

• Congenital adduction flexion contractures of thumbs and fingers, and clubfoot
• Characteristic face: large fontanelle, hypertelorism, short nose, long philtrum, micrognathia
• Hyperextensible, thin, fragile skin with atrophic scars and easy bruising
• Large subcutaneous haematomas
• Joint hypermobility, recurrent dislocation, kyphoscoliosis
• Ocular findings: myopia, strabismus, glaucoma, microcornea
• Cardiac valve disease, diverticular disease and bowel perforation
• Hydronephrosis, cryptorchidism, hearing loss

• Genetic testing of CHST14 and DSE, with deletion and duplication analysis.
• Biochemical studies: urinary glycosaminoglycan analysis showing increased chondroitin or dermatan sulphate ratios may support the diagnosis.
• Clinical evaluation: contractures, facial features and skin signs in a newborn.
• Cardiac imaging: echocardiography for valve regurgitation and aortic root.
• Abdominal and renal ultrasound: hydronephrosis, diverticula, and organ anomalies.
• Ophthalmology and audiology assessment.
• Brain imaging if there are neurological features.

Differential diagnosis.

• Classical Ehlers-Danlos syndrome
• Kyphoscoliotic Ehlers-Danlos syndrome
• Spondylodysplastic Ehlers-Danlos syndrome
• Arthrogryposis and Larsen syndrome
• Marfan syndrome and Beals syndrome
• Other congenital contracture syndromes

• Contractures and clubfoot: early serial casting and splinting, with physiotherapy, and surgery when casting fails (followed by careful soft tissue handling).
• Skin protection and wound care: avoid trauma, use padded clothing, and close wounds in two layers with sutures retained longer than usual (14 to 21 days).
• Haematomas: conservative management with rest, compression and monitoring for expansion. Drain only when tense or infected and with caution.
• Cardiac valve disease: monitor with echocardiography and treat heart failure in the usual way, with surgical valve repair or replacement for severe regurgitation.
• Bowel complications: a high fibre diet and laxatives such as macrogol 1 to 3 sachets daily to avoid straining, and surgical assessment for diverticulitis or perforation, using limited resection with stoma where needed.
• Renal care: treatment of hydronephrosis and urinary infection.
• Spine: bracing for progressive scoliosis, and cautious surgery.
• Eye and hearing care: correction of myopia, glaucoma treatment, hearing aids.
• Pain: paracetamol 1 g orally up to four times daily (maximum 4 g daily). Avoid NSAIDs because of bleeding tendency, and avoid long term opioids.
• Genetic counselling: each sibling of an affected child has a 25% chance of being affected.

Special groups.

• Surgery or invasive procedures: plan carefully, use soft tissue techniques and arrange blood availability.

Monitoring. Review skin, joints and development every 6 months in childhood. Echocardiography every 1 to 2 years. Abdominal and renal ultrasound every 1 to 2 years. Annual eye and hearing assessment.

Referral and escalation. Refer to clinical genetics, orthopaedics, cardiology and paediatric surgery. Emergency for severe abdominal pain, expanding haematoma, or signs of heart failure.