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 ... 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).
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 ... 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.