Collagen VI-related dystrophy is a group of disorders that affect skeletal muscles (which are the muscles used for movement) and connective tissue (which provides strength and flexibility to the skin, joints, and other structures throughout the body). Most affected individuals have muscle weakness and joint deformities called contractures that restrict movement of the affected joints and worsen over time. Researchers have described several forms of collagen VI-related dystrophy, which range in severity: Bethlem muscular dystrophy is the mildest, an intermediate form is moderate in severity, and Ullrich congenital muscular dystrophy is the most severe.

Variants (also known as mutations) in the COL6A1, COL6A2, and COL6A3 genes can cause the various forms of collagen VI-related dystrophy. These genes each provide instructions for making one component of a protein called type VI collagen. Type VI collagen makes up part of the extracellular matrix that surrounds muscle cells and connective tissue. This matrix is an intricate lattice that forms in the space between cells and provides structural support. The extracellular matrix is necessary for cell stability and growth. Research suggests that type VI collagen helps secure and organize the extracellular matrix by linking the matrix to the cells it surrounds.

Collagen VI-related dystrophy is rare. Bethlem muscular dystrophy is estimated to occur in 0.77 per 100,000 individuals, and Ullrich congenital muscular dystrophy is estimated to occur in 0.13 per 100,000 individuals. Only a few cases of the intermediate form have been described in the scientific literature.

Collagen VI-related dystrophy is often inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Bethlem muscular dystrophy is typically inherited in an autosomal dominant manner. The affected person usually inherits the variant from one affected parent. The intermediate form and  Ullrich congenital muscular dystrophy can also follow an autosomal dominant inheritance pattern. These forms typically result from new variants in the gene and occur in people with no history of the disorder in their family.

Published Date: July 19, 2022
Published By: National Institutes of Health