The natural course of Bethlem myopathy in five previously published kindreds and two novel pedigrees was investigated, with attention to the mode of onset in 23 children and the progression of weakness in 36 adult patients followed at the Academic Medical Center, Amsterdam, The Netherlands. Onset was characterized by diminished fetal movements, neonatal hypotonia and congenital contractures including torticollis, nearly all children exhibiting weakness or contractures and slightly delayed milestones during the first 2 years of life. Symptoms became more evident at 5 years of age, with worsening of contractures and weakness during childhood, followed by relative recovery during puberty. During early adult life, many patients were nearly asymptomatic except for contractures. From middle age onwards, the contractures remained constant but weakness and incapacity showed slow but ongoing progression into adulthood, more than two-thirds of patients over 50 years of age requiring a wheelchair. [1]

COMMENT. In 1976, Bethlem and van Wijngaarden described three families with an early-onset benign autosomal dominant myopathy with contractures. Contractures involved fingers, wrists, elbows, shoulders, knees and hips. Weakness was mild, affecting proximal and extensor muscles, with only limited functional impairment, even in old age. Cranial and cardiac muscles were not involved. Serum CPK was normal or slightly elevated and muscle biopsy changes were nonspecific. Subsequent reports included slightly variable manifestations, some children showing highly elevated CPK, up to 15 times normal, and muscle biopsies with dystrophic, necrotic and degenerating changes. Genetic tests find collagen type VI as the defective protein in Bethlem myopathy. The present study defines further variations in the clinical manifestations of the disease, with onset of symptoms at or even before birth, and a slowly progressive course in middle to late adulthood.