Alternative titles; symbols
ORPHA: 431272; DO: 0060253;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xq26.3 | Scapuloperoneal myopathy, X-linked dominant | 300695 | X-linked dominant | 3 | FHL1 | 300163 |
A number sign (#) is used with this entry because of evidence that X-linked dominant scapuloperoneal myopathy is caused by mutation in the FHL1 gene (300163).
Wilhelmsen et al. (1996) examined 44 members of an Italian-American family segregating scapuloperoneal muscular dystrophy which affected 14 individuals. The diagnosis of scapuloperoneal syndrome was based on clinical features including foot drop as an 'invariable early sign,' proximal arm weakness always preceding hand weakness, and scapular winging on examination of all patients. Serum creatine kinase (CK) levels were elevated in all patients. Quantitative electromyography as well as 2 autopsies demonstrated a myopathy with normal motor neurons and peripheral nerves. In the 2 autopsies there were hyaline desmin (125660)-containing cytoplasmic inclusions in combination with focal myopathic changes, possibly a specific marker of this disorder. There was no documented male-to-male transmission although 1 patient may have inherited the disease from his father who died while still at risk. Wilhelmsen et al. (1996) stated that focal atrophy in the muscle biopsy as well as inconclusive electromyography in other individuals could give rise to confusion of this disorder with neurogenic scapuloperoneal amyotrophy (see 181400 and 181405).
Quinzii et al. (2008) reevaluated the family originally reported by Wilhelmsen et al. (1996), including 14 affected individuals, 8 women and 6 men, in 5 generations. Two of these affected individuals had been considered unaffected in the previous report. Affected men had earlier age at onset than affected women, and were more severely affected.
Schessl et al. (2009) stated that muscle biopsies from patients from the family reported by Quinzii et al. (2008) had been reexamined and found to contain reducing bodies, suggesting that the phenotype in this family may represent a mild form of X-linked reducing body myopathy (300718).
Wilhelmsen et al. (1996) used linkage analysis to map scapuloperoneal myopathy in a large Italian-American family to chromosome 12q. Ten individuals classified as 'not affected' shared the chromosome 12q haplotype with affected individuals, suggesting incomplete penetrance, double recombination in these 'not affected' individuals, or false-positive linkage. Therefore, Quinzii et al. (2008) performed a new genomewide scan with microsatellite markers in leukocyte DNA from 27 family members (14 affected and 13 unaffected), which established linkage to chromosome Xq26.
In all affected members of the large family with scapuloperoneal myopathy originally reported by Wilhelmsen et al. (1996), Quinzii et al. (2008) detected a missense change (W122S; 300163.0001) in the FHL1 gene, encoding 4-and-a-half-LIM domains protein-1. The mutation alters a conserved residue in the second LIM domain of the protein. Affected males were hemizygous, and affected females heterozygous, for the mutation. This was the first report of X-linked dominant scapuloperoneal myopathy and the first human mutation in FHL1.
Quinzii, C. M., Vu, T. H., Min, K. C., Tanji, K., Barral, S., Grewal, R. P., Kattah, A., Camano, P., Otaegui, D., Kunimatsu, T., Blake, D. M., Wilhelmsen, K. C., Rowland, L. P., Hays, A. P., Bonilla, E., Hirano, M. X-linked dominant scapuloperoneal myopathy is due to mutation in the gene encoding four-and-a-half-LIM protein 1. Am. J. Hum. Genet. 82: 208-213, 2008. [PubMed: 18179901] [Full Text: https://doi.org/10.1016/j.ajhg.2007.09.013]
Schessl, J., Taratuto, A. L., Sewry, C., Battini, R., Chin, S. S., Maiti, B., Dubrovsky, A. L., Erro, M. G., Espada, G., Robertella, M., Saccoliti, M., Olmos, P., and 11 others. Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1. Brain 132: 452-464, 2009. [PubMed: 19181672] [Full Text: https://doi.org/10.1093/brain/awn325]
Wilhelmsen, K. C., Blake, D. M., Lynch, T., Mabutas, J., De Vera, M., Neystat, M., Bernstein, M., Hirano, M., Gilliam, T. C., Murphy, P. L., Sola, M. D., Bonilla, E., Schotland, D. L., Hays, A. P., Rowland, L. P. Chromosome 12-linked autosomal dominant scapuloperoneal muscular dystrophy. Ann. Neurol. 39: 507-520, 1996. [PubMed: 8619529] [Full Text: https://doi.org/10.1002/ana.410390413]