Bethlem myopathy: a slowly progressive congenital muscular dystrophy with contractures

Abstract

Bethlem myopathy is an early-onset benign autosomal dominant myopathy with contractures caused by mutations in collagen type VI genes. It has been reported that onset occurs in early childhood. We investigated the natural course of Bethlem myopathy in five previously published kindreds and two novel pedigrees, with particular attention to the mode of onset in 23 children and the progression of weakness in 36 adult patients. Our analysis shows that nearly all children exhibit weakness or contractures during the first 2 years of life. Early features include diminished foetal movements, neonatal hypotonia and congenital contractures which are of a dynamic nature during childhood. The course of Bethlem myopathy in adult patients is less benign than previously thought. Due to slow but ongoing progression, more than two-thirds of patients over 50 years of age use a wheelchair.

A novel de novo COL6A1 mutation emphasizes the role of intron 14 donor splice site defects as a cause of moderate-progressive form of ColVI myopathy – a case report and review of the genotype–phenotype correlation

“…At this moment we cannot predict the progression of her disease. However, hip contractures, scoliosis, head dropping and pronounced distal laxity might indicate an uncertain prognosis regarding preservation of independent movement in adulthood [10]. If this was the case, we would classify the patient in the intermediate group, with a moderate-progressive course.…”

COL6A3 Protein Deficiency in Mice Leads to Muscle and Tendon Defects Similar to Human Collagen VI Congenital Muscular Dystrophy

“…Bethlem myopathy is characterized by mild to moderate muscle weakness and multiple progressive joint contractures, mainly affecting the fingers, wrists, elbows, and ankles. It is a slowly progressive disorder and about a half of the Bethlem myopathy patients need aids for mobility after age 50 years (16).…”

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.…”