Adams-Oliver Syndrome 6

A number sign (#) is used with this entry because of evidence that Adams-Oliver syndrome-6 (AOS6) is caused by heterozygous mutation in the DLL4 gene (605185) on chromosome 15q15.

Description

Adams-Oliver syndrome is a rare developmental disorder defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly). In addition, vascular anomalies such as cutis marmorata telangiectatica congenita, pulmonary hypertension, portal hypertension, and retinal hypervascularization are recurrent findings. Congenital heart defects have been estimated to be present in 20% of AOS patients; reported malformations include ventricular septal defects, anomalies of the great arteries and their valves, and tetralogy of Fallot (summary by Stittrich et al., 2014).

For a discussion of genetic heterogeneity of Adams-Oliver syndrome, see AOS1 (100300).

Molecular Genetics

Meester et al. (2015) screened 91 families with Adams-Oliver syndrome for mutations in the candidate gene DLL4 and identified heterozygous nonsense and missense mutations in 9 families (see, e.g., 605185.0001-605185.0006). Noting the marked intrafamilial variability in phenotypic expression, with some parents exhibiting isolated aplasia cutis congenita whereas their offspring were severely affected, Meester et al. (2015) suggested that other genetic, epigenetic, or environmental factors might be involved in the clinical expression of the disease. Incomplete penetrance was also observed in some families.