Benign Myopathy, With Autosomal Dominant Inheritance

Abstract

Three pedigrees are described in which 28 living siblings suffered from a benign myopathy. The first symptoms were observed around the fifth year of life. The proximal muscles were more involved than the distal muscles, the extensors more than the flexors. Due to a marked paresis of the extensor digitorum communis muscles 22 patients showed a flexion contracture of the interphalangeal joints of the last four fingers. In addition 20 patients showed a flexion contracture of the elbows and 12 patients had a plantar flexion contracture of the ankles. A high incidence of congenital torticollis was found. The histopathological features were non-specific and remarkably uniform and consisted of a marked variation in muslce fibre diameter and a very marked increase of fatty tissue. Light-microscopy and electronmicroscopy did not show any specific structural changes. There was normal distribution of type I and type II fibres, without type-grouping or preferential atrophy of one of the fibre types. Lobulated type I fibres were found in 6 out of 12 biopsies. Post-mortem study of one case did not show any convincing features of a neurogenic disorder. As no relationship could be found between the siblings of the 3 pedigrees as far back as the beginning of the eighteenth century, this myopathy seemed to be a new nosological entity.

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

“…Mutations in the genes that codify the three collagen VI subunits lead to the second most common form of CMD, Ullrich atonic-sclerotic CMD [72][73][74][75] and to Bethlem myopathy 76,77 that now is included into CMD classification 8 .…”

“…3), and Col6A3 (2 q37) that encode respectively the alpha-1, alpha-2 and alpha-3 chains of collagen VI, cause two types of muscle disorders: Bethlem myopathy, with mild or moderate phenotype, and Ullrich CMD, with severe phenotype [1][2][3][4]6,7,69,117 . Bethlem myopathy is a slowly progressive disorder with variable age of onset, congenital or within the first or second decade of life, and marked flexion contractures of several joints 7,69,76,77,[117][118][119] . Ullrich CMD is an early onset condition with severe weakness and progressive course that manifests proximal joint contractures and marked distal hyperlaxity.…”

Therapy of Collagen VI-Related Myopathies (Bethlem and Ullrich)

“…Mutations in the genes encoding collagen VI (COL6A1, COL6A2, and COL6A3) cause the collagen VI-related myopathies, which comprise two major clinical forms, Bethlem myopathy (BM [MIM 158810]) 1 and Ullrich congenital muscular dystrophy (UCMD [MIM 254090]), 2 but also the limb girdle 3 and the myosclerosis variants. 4 Bethlem myopathy is an autosomal dominant disorder characterized by slowly progressive axial and proximal muscle weakness with finger flexion contractures.…”

Bethlem myopathy (BETHLEM) and Ullrich scleroatonic muscular dystrophy: 100th ENMC International Workshop, 23–24 November 2001, Naarden, The Netherlands

“…Bethlem myopathy (OMIM # 158810) is an early-onset benign myopathy characterized by proximal muscle weakness and multiple flexion contractures [1][2][3]. It is caused by dominant mutations in COL6A1 (OMIM # 120220), COL6A2 (OMIM # 120240) [4], and COL6A3 (OMIM # 120250) [5] genes.…”