Fibular aplasia with ectrodactyly

Abstract

Fibular aplasia with split hand/foot or other defects of the central axis is a rare disorder that shares several characteristics with the better known tibial aplasia-ectrodactyly syndrome. They appear to be inherited in an autosomal dominant fashion. In both, however, the phenotype is markedly variable, penetrance is reduced, and apparently sporadic cases are relatively frequent. We report a new case of this disorder and review the clinical and demographic findings in 47 others identified from the literature or other sources. A key observation was that the sex ratio is biased toward males, especially in apparently sporadic cases. This male bias is largely explained by a lower penetrance rate in women. Both affected males and females had affected children, but the risk to offspring was higher when the mother carried the gene, in keeping with a mixed model for genetic susceptibility, i.e., the penetrance of the major predisposing gene is acting against a multifactorially determined level of liability. Given the high degree of nonpenetrance and very variable expressivity, counseling with respect to recurrence risk is problematic and will likely remain so, even when the major predisposing gene is identified.