Alternative titles; symbols
SNOMEDCT: 763895001; ORPHA: 289380;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 21q22.3 | ?Myosclerosis, congenital | 255600 | Autosomal recessive | 3 | COL6A2 | 120240 |
A number sign (#) is used with this entry because of evidence that autosomal recessive myosclerosis is caused by homozygous mutation in the COL6A2 gene (120240). One such family has been reported.
Lowenthal (1954) described symmetrical congenital contractures of the joints in 4 sibs, offspring of normal parents. Sclerosis of both muscle and skin was thought to be present.
Merlini et al. (2008) reported 2 sibs, born of consanguineous parents, with a phenotype consistent with myosclerosis. The boy showed difficulty in running and climbing stairs and had Achilles tendon contractures during early childhood. This was followed by progressive contractures of all joints, including jaws, spine, shoulders, elbows, wrists, fingers, hips, and knees. On examination at age 21, he was short with mild thoracolumbar scoliosis, accentuated lumbar lordosis, mild facial weakness, mild girdle and proximal limb weakness, and moderate distal weakness. The muscles were thin and sclerotic on palpation. He had diffuse restriction of movements of all joints and was severely limited by the contractures. His sister developed progressive contractures after age 4 years, necessitating Achilles tendon release. At age 17, she had diffuse and severe contractures involving the jaw, spine, upper and lower girdles, and proximal and distal limb joints. Her muscles were thin and of a woody consistency. Both patients had increased serum creatine kinase. Skeletal muscle biopsies showed a myopathic pattern with fibrosis, proliferation of endomysial and perimysial connective tissue, variation of myofiber diameter, and internal nuclei. Staining for collagen VI revealed a discontinuous distribution at the basal lamina of myofibers, and Western blot confirmed decreased amounts of collagen VI.
The transmission pattern of myosclerosis in the family reported by Merlini et al. (2008) was consistent with autosomal recessive inheritance.
In 2 sibs with myosclerosis, Merlini et al. (2008) identified a homozygous truncating mutation in the COL6A2 gene (120240.0011). The unaffected parents were heterozygous for the mutation.
Lowenthal, A. Un groupe heredodegeneratif nouveau: les myoscleroses heredofamiliales. Acta Neurol. Psychiat. Belg. 54: 155-165, 1954. [PubMed: 13157969]
Merlini, L., Martoni, E., Grumati, P., Sabatelli, P., Squarzoni, S., Urciuolo, A., Ferlini, A., Gualandi, F., Bonaldo, P. Autosomal recessive myosclerosis myopathy is a collagen VI disorder. Neurology 71: 1245-1253, 2008. [PubMed: 18852439] [Full Text: https://doi.org/10.1212/01.wnl.0000327611.01687.5e]