Abstract
Mutations in the genes COL6A1, COL6A2, and COL6A3, coding for three α chains of collagen type VI, underlie a spectrum of myopathies, ranging from the severe congenital muscular dystrophy-type Ullrich (UCMD) to the milder Bethlem myopathy (BM), with disease manifestations of intermediate severity in between. UCMD is characterized by early-onset weakness, associated with pronounced distal joint hyperlaxity and the early onset or early progression of more proximal contractures. In the most severe cases ambulation is not achieved, or it may be achieved only for a limited period of time. BM may be of early or later onset, but is milder in its manifestations, typically allowing for ambulation well into adulthood, whereas typical joint contractures are frequently prominent. A genetic spectrum is emerging, with BM being caused mostly by dominantly acting mutations, although rarely recessive inheritance of BM is also possible, whereas both dominantly as well as recessively acting mutations underlie UCMD.