Genetics of human left-right axis malformations

Abstract

Like all vertebrates, humans establish anatomic left-right asymmetry during embryogenesis. Variation from this normal arrangement (situs solitus) results in heterotaxy, expressed either as randomization (situs ambiguus) or complete reversal (situs inversus) of normal organ position. Familial heterotaxy occurs with autosomal dominant, recessive, and X-linked inheritance. All possible situs variants--solitus, ambiguus, inversus--can appear among some heterotaxy families. Positional cloning has led to the identification of a gene on the X chromosome responsible for some cases of human heterotaxy. In addition to their medical relevance, human studies provide a unique contribution to our understanding of left-right axis development among all vertebrates.