Genetics of congenital nemaline myopathy

Family patterns for 50 reported probands with congenital nemaline myopathy were compared with expected patterns derived from various possible genetic hypotheses. The disease had a high mortality in childhood but remained clinically stationary after this period. Some normal relatives showed nemaline rods on muscle biopsy. Chromosomes were normal in the two cases in which they were examined. Prenatal exposures appeared irrelevant to this disease. Autosomal recessive and X-linked recessive or dominant modes of inheritance were not compatible with the observed patterns, which could be explained by an autosomal dominant mode with a reduced penetrance. Normal relatives who carried rods were presumably unaffected heterozygotes of the same gene. The genetic ratio (the proportion of affected siblings) was 0.3, being short of the expected value, 0.5, probably because of the presence of these asymptomatic rod-bearing heterozygotes. While the pressure of natural selection was great in the patients who died or were severely disabled, the gene could be passed to the next generation by mildly affected patients or heterozygotes who remained unaffected.