DLL4

Adams-Oliver syndrome

At least nine DLL4 gene mutations have been found in people with Adams-Oliver syndrome, a condition characterized by areas of missing skin (aplasia cutis congenita), usually on the scalp, and malformations of the hands and feet. Some of these mutations lead to production of an abnormally short protein that is likely broken down quickly, causing a shortage of DLL4. Other mutations change single protein building blocks (amino acids) in the DLL4 protein. These changes are thought to alter the structure of the protein, impairing its ability to function. Loss of DLL4 function may underlie blood vessel abnormalities in people with Adams-Oliver syndrome; however, some people with DLL4-related Adams-Oliver syndrome do not have these abnormalities. It is not clear how loss of DLL4 function leads to the scalp and limb abnormalities characteristic of the condition. Researchers suggest these features may be due to abnormal blood vessel development before birth.