Congenital Muscular Dystrophy, Ullrich Type

Ullrich congenital muscular dystrophy (UCMD) is characterized by early-onset, generalized and slowly progressive muscle weakness, multiple proximal joint contractures, marked hypermobility of the distal joints and normal intelligence.

Epidemiology

Less than 50 molecularly confirmed cases have been reported worldwide.

Clinical description

Weakness of the facial muscles, a high-arched palate, congenital hip dislocation, protrusion of the calcaneus, torticollis, transient kyphotic deformity, contractures (particularly involving the elbows and knees), and distal laxity (involving the hands, feet, and fingers) may be the neonatal findings. Motor milestones are delayed. The distal joints of the hands, ankles, toes, and fingers show lifelong hyperextensibility, but with age the distal hyperlaxity can give way to marked long lasting finger flexion contractures and tight Achilles tendons. Failure to thrive is frequent. Early in the disease course, most contractures release spontaneously but recur over the years. With progression of the disease, spinal rigidity and scoliosis typically develop (in the first or second decade of life). UCMD patients usually have dry soft skin and follicular hyperkeratosis over the extensor surfaces of the extremities. Early respiratory failure is a common complication and potential cause of death.

Etiology

UCMD is caused by mutations in the genes coding for the alpha chains of collagen VI (COL6A1, COL6A2, and COL6A3) and is transmitted in an autosomal recessive manner.

Diagnostic methods

Diagnosis is based on patient history and recognition of the typical clinical features. Laboratory studies may show that serum creatine kinase concentrations are normal or mildly increased. Muscle biopsy typically shows complete or partial absence of collagen VI immunolabeling. Detection of mutations in the three collagen VI genes is the gold standard for diagnosis.

Differential diagnosis

In the neonatal period, the differential diagnoses include Bethlem myopathy and other forms of congenitalmuscular dystrophy (CMD) and myopathy, spinal muscular atrophy, forms of Ehlers-Danlos syndrome, and Marfan syndrome (see these terms). Some CMD subtypes such as merosin-deficient congenital muscular dystrophy (MDC1A), Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama CMD (see these terms) should also be considered, although in these disorders intellectual deficit is a major symptom.

Antenatal diagnosis

Prenatal diagnosis is feasible.

Management and treatment

Currently, there is no curative therapy, but supportive treatment can dramatically improve the quality of life of patients with UCMD. Physiotherapy, early mobilization, regular stretching and splinting are the main forms supportive care. Respiratory support with nocturnal ventilation usually becomes necessary in the first or second decade of life. Prophylaxis of chest infections and timely use of antibiotics is mandatory. Feeding by gastrostomy, surgical release of the contractures and surgery to prevent progression of scoliosis may be needed. It has recently been shown that UCMD patients may benefit from cyclosporin A.

Prognosis

UCMD is a severe progressive disorder. Most patients are unable to walk or manage to walk for only a short period of time, usually before puberty. Children can stand and walk with the aid of leg splints.