Association of Adams-Oliver syndrome with pulmonary arterio-venous malformation in the same family: A further support to the vascular hypothesis

Abstract

Adams-Oliver syndrome (AOS) is a rare disease characterized by congenital scalp defects, terminal transverse limb defects and cutis marmorata telangiectatica. A significant incidence of cardiac and vascular malformations has been reported, leading to the hypothesis of a vascular defect early involved in the pathogenesis. We report two members of the same family with previously diagnosed AOS based on clinical phenotype and later recognized to have pulmonary arterio-venous malformation (PAVM). None of the subjects fulfilled current diagnostic criteria of hereditary hemorrhagic telangiectasia, which is the most common cause of PAVM. The occurrence of PAVM in AOS lends support to the hypothesis that endothelial specific abnormalities could be a patho-physiological mechanism in its development. Therefore, the role of screening for PAVM in clinical management of subjects with AOS should deserve further studies.

Adams–Oliver syndrome: further evidence of an autosomal recessive variant

“…Cardiovascular anomalies were described in AOS (Zapata et al, 1995;Lin et al, 1998;Sankhyan et al, 2006), yet none of our patients had cardiac lesions or echocardiography changes. Pulmonary hypertension and pulmonary arterioveneous malformations were reported by Toriello et al (1988), Swartz et al (1999), Piazza et al (2004) and Maniscalco et al (2005) but were not present in our patients, yet follow-up is carried out owing to the potentially hazardous complications of such associations. Farrell et al (1993) described a sporadic case of AOS with ASD, chylothorax and chronic juvenile myelogeneous leukemia.…”

“…Many theories explain the associated physical anomalies in AOS by implicating in-utero vascular insufficiency or compromise (Toriello et al, 1988;Jaeggi et al, 1990;Fryns et al, 1996;Maniscalco et al, 2005). The vascular anomaly could be the result of a gene defect that seems to express a predisposition for a vasculopathy (Piazza et al, 2004).…”

“…Interfamilial variability exists in relation to the presence of abnormalities including scalp and limb defects (Amor et al, 2000;Verdyck et al, 2006). Most described cases supported autosomal dominant inheritance (Bonafede and Beighton, 1979;Kuster et al, 1988;Maniscalco et al, 2005;Verdyck et al, 2006). The syndrome is characterized by variability of expression and reduced penetrance in some cases (Scribanu and Temtamy, 1975).…”

A Rare de novo Interstitial Duplication at 4p15.2 in a Boy with Severe Congenital Heart Defects, Limb Anomalies, Hypogonadism, and Global Developmental Delay

“…RBPJ is known to be a transcription factor in the Notch/RBPJ signaling pathway and plays an important role in neurodevelopment. Haploinsufficiency of the RBPJ gene causes Adams-Oliver syndrome 3, AOS3 (MIM 614814), a rare dominant genetic condition, characterized by aplasia cutis congenita, transverse terminal limb defects, cutis marmorata telangiectatica congenita, and cardiovascular malformations [Lin et al, 1998;Maniscalco et al, 2005;Snape et al, 2009;Algaze et al, 2013]. In addition, numerous studies indicate that Notch signaling in Sertoli cells is crucial for proper regulation of the testis stem cell niche essential for directing the population size and differentiation fate of spermatogonial stem cells [Kitadate et al, 2010;Garcia et al, , 2014.…”

Adams-Oliver syndrome associated with bilateral anterior polar cataracts and optic disk drusen

“…5 The role of early embryonic vascular disruption, as one of the underlying causes of AOS, is further supported by the occurrence of vascular malformations in this syndrome, including cutis marmorata telangiectatica congenita and abnormal pulmonary and portal vasculature. 6 Postmortem examination of an AOS patient with pulmonary hypertension revealed abnormalities in the vascular smooth muscle cells and pericyte coverage of the vasculature associated with vessel dilatation (pericyte absence) or stenosis (pericyte hyperproliferation). 2 Vascular disruption associated with AOS may cause developmental abnormalities with an early arrest in the lens cell differentiation, leading to the formation of cataracts.…”