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Incidence

It is an extremely rare disorder, with fewer than 100 families worldwide known to have it. Bethlem myopathy is estimated to occur in 1 in 200,000 individuals. It is an autosomal dominant myopathy. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. Rarely, this condition is inherited in an autosomal recessive pattern.

Clinical Characteristics

It is an autosomal dominant myopathy, classified as a congenital form of muscular dystrophy, that is caused by a variation in one of the three genes coding for type VI collagen. These include COL6A1, COL6A2, and COL6A3. The clinical picture is characterized by proximal weakness and wasting of the limb girdle associated with mild contractures of the fingers and other joints. The clinical features do not differ markedly from those of other mild forms of progressive muscular dystrophy with the exception of finger contractures, which are sometimes suggestive of the diagnosis. Onset is usually in early childhood, sometimes at birth (with congenital torticollis as the presenting symptom). Hypotonia and mild muscle weakness in proximal rather than distal muscles is often noted. Contractures are an almost constant feature in this condition and occur predominantly in the fingers, elbows, knees and ankles. They are highly suggestive of the diagnosis, when they involve the interphalangeal joints of the last 4 fingers. This myopathy is a benign form of autosomal dominant muscular dystrophy (MD). It generates mild clinical symptoms with proximal muscle weakness and early contractures notably in the fingers. The slow progression of the disease and the absence of pseudohypertrophic calves and cardiomyopathy are distinctive features. Progression is slow and occasionally leads the patient to be wheelchair-bound after 25 to 40 years of evolution. The disease course, most often slow, may vary from one individual to another, even within the same family. Respiratory involvement is not a cardinal feature and is rarely reported. Routine laboratory findings are not very informative. Serum CK levels are often normal or slightly elevated. Electromyographic studies show a myopathic pattern. Muscle histology demonstrates a non-specific myopathy with fiber-size variation, few necrotic/regenerative fibers and a mild increase of connective tissue, all these features appearing mild to moderate. The diagnosis is based on clinical findings and should be confirmed at the molecular level whenever possible.

Precipitants

None

Provocation Tests

None

Diagnostic Procedures

The diagnosis is first considered at the clinical level. Muscle imaging may contribute to assessing the selectivity of muscle involvement. Routine tests (CK, EMG) are not very specific. Mutations in one of the 3 subunits of collagen VI can be investigated only in a few specialized laboratories. These include COL6A1, COL6A2, and COL6A3. The diagnosis is based on clinical findings and should be confirmed at the molecular level whenever possible.