Adams–Oliver syndrome review of the literature: Refining the diagnostic phenotype

Abstract

The Adams-Oliver syndrome (AOS) is defined as aplasia cutis congenita (ACC) with transverse terminal limb defects (TTLD). Frequencies of associated anomalies are not well characterized. Six causative genes have been identified: ARHGAP31, DOCK6, EOGT, RBPJ, NOTCH1, and DLL4. We review 385 previously described individuals (139 non-familial and 246 familial probands and family members) and add clinical data on 13 previously unreported individuals with AOS. In addition to ACC and TTLD, the most commonly associated anomalies included a wide variety of central nervous system (CNS) anomalies and congenital heart defects each seen in 23%. CNS anomalies included structural anomalies, microcephaly, vascular defects, and vascular sequelae. CNS migration defects were common. Cutis marmorata telangiectasia congenita (CMTC) was found in 19% of the study population and other vascular anomalies were seen in 14%. Hemorrhage was listed as the cause of death for five of 25 deaths reported. A relatively large number of non-familial probands were reported to have hepatoportal sclerosis with portal hypertension and esophageal varices. Non-familial probands were more likely to have additional anomalies than were familial probands. The data reported herein provide a basis for refining the diagnostic features of AOS and suggest management recommendations for probands newly diagnosed with AOS. © 2017 Wiley Periodicals, Inc.

Effects of Notch glycosylation on health and diseases

“…Adams-Oliver syndrome (AOS) is a rare disease that is characterized by defects in the skin and bones of the parietal region and transverse defects of the extremities and is accompanied by vascular abnormalities (Hassed, Li, Mulvihill, Aston, & Palmer, 2017). Although the molecular mechanism including the causative gene ( …”

“…Adams-Oliver syndrome (AOS) is a rare disease that is characterized by defects in the skin and bones of the parietal region and transverse defects of the extremities and is accompanied by vascular abnormalities (Hassed, Li, Mulvihill, Aston, & Palmer, 2017). Although the molecular mechanism including the causative gene(s) of AOS remained unknown for a long time, Notch signaling-related factors, such as NOTCH1 Stittrich et al, 2014), DLL4 (Aminkeng, 2015;Meester et al, 2015), EOGT (Cohen et al, 2014;Shaheen et al, 2013), and RBP-J (Hassed et al, 2012) have recently been reported as the causative genes in this condition.…”

Integration of Drosophila and Human Genetics to Understand Notch Signaling Related Diseases

“…Adams-Oliver syndrome (AOS) is a developmental disorder characterized by aplasia cutis congenital (a congenital skin defect, typically of the scalp) and transverse limb defects (typically digital amputations) [293,294]. In addition, some AOS patients exhibit nervous system and cardiac/vascular abnormalities.…”

Current opinion in the molecular genetics of Adams-Oliver syndrome

“…[3,4] Congenital heart defects (CHDs) are detected in 23% of cases and represent significant morbidity and mortality. [2,5] AOS-related CHDs cover a wide range of severity, predominantly encompassing leftsided obstructive defects, and are often associated with vascular abnormalities, the most frequent of which is cutis marmorata telangiectatica congenita (CMTC). Other vascular defects may impact the lower limb vasculature, portal and cortical renal veins, or the pulmonary vasculature.…”

“…[7] Abnormalities of the central nervous system (CNS) and structural eye anomalies, for example microphthalmia and retinal vasculopathy, appear more commonly associated with autosomal recessive inheritance. [2,5,8] Developmental delay and seizures each occur in 8-9% of AOS cases overall, but are significantly more frequent (>45%) in patients with microcephaly and are strongly correlated with intracranial vascular defects. [5,9] Additional developmental defects manifesting in <2% of cases include gastrointestinal, renal or reproductive anomalies and facial dysmorphism.…”