is unknown. Similar terminal transverse limb anomalies and cardiovascular malformations are seen in animal models of hypoxic insults during the first trimester. Combined with the common association of cardiac and vascular abnormalities in AOS, it has been hypothesized that the spectrum of defects observed in AOS could be due to a disorder of vasculogenesis. In rare cases, AOS can be associated with chromosomal translocations. A panel of candidate genes (including ALX4, ALX1, MSX1, MSX2, P63, RUNX2 and HOXD13) were tested but no disease-causing mutations were identified. More recently, mutations in six genes have been identified, highlighting the Rho family of GTPases and the Notch signalling pathway as important factors in the pathogenesis of AOS. Diagnosis The diagnosis of AOS is a clinical diagnosis based on the specific features described above. A system of major and minor criteria was proposed. The combination of two major criteria would be sufficient for the diagnosis of AOS, while a combination of one major and one minor feature would be suggestive of AOS. Genetic testing can be performed to test for the presence of mutation in one of the known genes, but these so far only account for an estimated 50% of patients with AOS. A definitive diagnosis may therefore not be achieved in all cases. Management Management of AOS is largely symptomatic and aimed at treating the various congenital anomalies present in the individual. When the scalp and/or cranial bone defects are severe, early surgical intervention with grafting is indicated. Prognosis The overall prognosis is excellent in most cases. Most children with Adams–Oliver syndrome can likely expect to have a normal life span. However, individuals with more severe scalp and cranial defects may experience complications such as hemorrhage and meningitis, leading to long-term disability. Epidemiology AOS is a rare genetic disorder and the annual incidence or overall prevalence of AOS is unknown. Between 100-200 individuals with this disorder have been reported in the medical literature. It's estimated to affect approximately 1 in every 225,000 live births. History AOS was first reported by the American pediatric cardiologist Forrest H. Adams and the clinical geneticist Clarence Paul Oliver in a family with eight affected members. Citations References External links Genodermatoses Rare genetic syndromes Syndromes affecting the nervous system Genetic disorders with OMIM but no gene Syndromes affecting the skin Diseases named for discoverer