Ullrich Congenital Muscular Dystrophy

Ullrich congenital muscular dystrophy is the severe form of collagen VI-related muscular dystrophy (COL6A1, COL6A2, COL6A3), with neonatal hypotonia, distal joint hyperlaxity, proximal contractures and progressive respiratory failure. Inheritance is recessive or de novo dominant.

Pathophysiology. Severe collagen VI deficiency or dominant negative variants disrupt the extracellular matrix, causing muscle fibre loss and fibrosis.

Neonatal hypotonia, congenital hip dislocation, torticollis, distal hyperlaxity with proximal contractures (hips, knees, elbows), kyphoscoliosis, protruding calcanei, soft palmar skin, keloid scarring and follicular hyperkeratosis. Motor milestones are delayed, with some achieving walking and later loss before adulthood. Respiratory failure appears in the first or second decade. Cognition is normal.

Red flags.

• Nocturnal hypoventilation, morning headache or recurrent chest infection.
• Rapidly progressive scoliosis.

Creatine kinase is normal or mildly raised. Muscle MRI shows rim sign and central shadow. Muscle biopsy and immunostaining of collagen VI (muscle and fibroblasts) show deficiency. Genetic testing of COL6 genes confirms the diagnosis. Assess pulmonary function, sleep study, echocardiography and spine imaging.

Differential diagnosis.

• Bethlem myopathy, rigid spine syndrome (SEPN1) and Emery-Dreifuss muscular dystrophy.
• Other congenital muscular dystrophies, spinal muscular atrophy and Pompe disease.

Respiratory care. Overnight oximetry and capnography, non-invasive ventilation as soon as hypoventilation appears, cough assistance, vaccination and early antibiotic treatment of chest infections. Tracheostomy in some cases.

Orthopaedic. Stretching, bracing, treatment of hip dislocation and scoliosis, and foot care. Contracture surgery needs caution because of keloid and wound healing issues.

Nutrition. Dietitian review, and gastrostomy if growth falters.

Cardiac. Baseline echocardiography, with cardiology follow up as indicated.

Support. Education, psychosocial support and palliative care planning in severe cases.

Monitoring. Respiratory function every 6 months, spine and growth.

Referral and escalation. Refer to paediatric neuromuscular, respiratory and orthopaedic services.

Special groups. Genetic counselling for families and prenatal testing.