The spectra of clinical phenotypes in aplasia cutis congenita and terminal transverse limb defects

Abstract

The combination of aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLD) is often referred to as the eponymous Adams-Oliver syndrome (AOS). The molecular basis of this disorder remains unknown, although the common occurrence of cardiac and vascular anomalies suggests a primary defect of vasculogenesis. Through the description of three previously unreported affected individuals, ascertained through the Adams-Oliver Syndrome European Consortium, we illustrate the phenotypic variability characteristically observed within extended families with AOS. Taken in combination with a detailed review of the available literature, we provide evidence for distinct clinical entities within the ACC/TTLD spectrum, which may reflect genetic heterogeneity within this spectrum of disorders.