SNOMEDCT: 782675008; ORPHA: 178400; DO: 0111187;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2p13.2 | Myopathy, distal, with anterior tibial onset | 606768 | Autosomal recessive | 3 | DYSF | 603009 |
A number sign (#) is used with this entry because of evidence that distal myopathy with anterior tibial onset (DMAT) is caused by homozygous mutation in the gene encoding dysferlin (DYSF; 603009) on chromosome 2p13.
Mutations in the DYSF gene also cause Miyoshi myopathy (MMD1; 254130) and autosomal recessive limb-girdle muscular dystrophy-2 (LGMDR2; 253601).
Distal myopathy with anterior tibial onset (DMAT) is an autosomal recessive muscle disorder with onset of anterior tibial weakness in the second or third decade of life. The disease course progresses rapidly to include lower and upper proximal muscles, necessitating use of a wheelchair 11 to 22 years from onset (Illa et al., 2001).
Liu et al. (1998) and Illa et al. (2001) described a novel form of autosomal recessive distal myopathy in a consanguineous Spanish family. Onset of the disorder is between 14 and 28 years of age and the anterior tibial muscles are the first muscle group to be involved. The disorder has a rapidly progressive course successively involving the lower and upper proximal muscles, with patients being confined to a wheelchair 11 to 22 years from onset. The cranial muscles are spared. Serum creatine kinase level is increased 20 to 70 times the normal value and muscle histopathologic studies show moderate myopathic changes without vacuoles. The disorder is similar to Nonaka myopathy (605820) in that onset occurs in the anterior tibial muscles, but is distinguished clinically from that disorder by the high creatine kinase levels and the absence of vacuoles in the muscle biopsies.
The transmission pattern of DMAT in the Spanish family reported by Liu et al. (1998) was consistent with autosomal recessive inheritance.
In affected members of a Spanish family with distal myopathy with anterior tibial onset, Liu et al. (1998) identified a 5966delG mutation in the DYSF gene (603009.0002). This mutation yields an absence of dysferlin on the sarcolemma of muscle fibers in affected patients.
In affected members of 2 families from Sueca, Spain, with DMAT, Vilchez et al. (2005) identified a homozygous missense mutation in the DYSF gene (R1905X; 603009.0012).
Illa, I., Serrano-Munuera, C., Gallardo, E., Lasa, A., Rojas-Garcia, R., Palmer, J., Gallano, P., Baiget, M., Matsuda, C., Brown, R. H. Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype. Ann. Neurol. 49: 130-134, 2001. [PubMed: 11198284]
Liu, J., Aoki, M., Illa, I., Wu, C., Fardeau, M., Angelini, C., Serrano, C., Urtizberea, J. A., Hentati, F., Ben Hamida, M., Bohlega, S., Culper, E. J., Amato, A. A., Bossie, K., Oeltjen, J., Bejaoui, K., McKenna-Yasek, D., Hosler, B. A., Schurr, E., Arahata, K., de Jong, P. J., Brown, R. H., Jr. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nature Genet. 20: 31-36, 1998. [PubMed: 9731526] [Full Text: https://doi.org/10.1038/1682]
Vilchez, J. J., Gallano, P., Gallardo, E., Lasa, A., Rojas-Garcia, R., Freixas, A., De Luna, N., Calafell, F., Sevilla, T., Mayordomo, F., Baiget, M., Illa, I. Identification of a novel founder mutation in the DYSF gene causing clinical variability in the Spanish population. Arch. Neurol. 62: 1256-1259, 2005. [PubMed: 16087766] [Full Text: https://doi.org/10.1001/archneur.62.8.1256]