Adams–Oliver syndrome and portal hypertension: Fortuitous association or common mechanism?

Silva, Gisela; Braga, Alexandre; Leitão, Banquart; Mesquita, Abel; Reis, Aldina; Duarte, Carlos; Barbot, José; Silva, Ermelinda Santos

doi:10.1002/ajmg.a.34435

Cited by 4 publications

(5 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The clinical phenotype of 3-II-1 from family 3 was described in detail by Silva et al 12 In summary, this now 14-year-old boy was affected by aplasia of the scalp, underlying cranial defect, cutis marmorata, brachysyndactyly of the toes, hypoplastic fingernails, inguinal and umbilical hernias, mild pulmonary stenosis, and hypoplasia of the intrahepatic portal venous tree. He developed portal venous thrombosis in infancy, which led to symptomatic portal hypertension; a mesenteroportal shunt was placed, but this was also complicated by thrombosis.…”

mentioning

confidence: 73%

“…Necrotic, hemorrhagic digits have also been observed in a preterm neonate with AOS, in keeping with the notion that some of the limb defects in AOS might be due to a NOTCH1-related vasculopathy. 49 Underbranching of vasculature trees, irregular vascular smooth muscle cell coverage, tortuous ectatic vessels, and a general paucity of small to medium blood vessels are key features of the AOS vasculopathy 12,47 and might also explain other symptoms observed with AOS, including CNS microbleeds, retinopathy and visual impairment due to failed retinal vascularization, portal hypertension, ischemic bowel disease, placental insufficiency, and pulmonary hypertension.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Mutations in NOTCH1 Cause Adams-Oliver Syndrome

Stittrich

Lehman

Bodian

et al. 2014

The American Journal of Human Genetics

155

132

View full text Add to dashboard Cite

Notch signaling determines and reinforces cell fate in bilaterally symmetric multicellular eukaryotes. Despite the involvement of Notch in many key developmental systems, human mutations in Notch signaling components have mainly been described in disorders with vascular and bone effects. Here, we report five heterozygous NOTCH1 variants in unrelated individuals with Adams-Oliver syndrome (AOS), a rare disease with major features of aplasia cutis of the scalp and terminal transverse limb defects. Using whole-genome sequencing in a cohort of 11 families lacking mutations in the four genes with known roles in AOS pathology (ARHGAP31, RBPJ, DOCK6, and EOGT), we found a heterozygous de novo 85 kb deletion spanning the NOTCH1 5' region and three coding variants (c.1285T>C [p.Cys429Arg], c.4487G>A [p.Cys1496Tyr], and c.5965G>A [p.Asp1989Asn]), two of which are de novo, in four unrelated probands. In a fifth family, we identified a heterozygous canonical splice-site variant (c.743-1 G>T) in an affected father and daughter. These variants were not present in 5,077 in-house control genomes or in public databases. In keeping with the prominent developmental role described for Notch1 in mouse vasculature, we observed cardiac and multiple vascular defects in four of the five families. We propose that the limb and scalp defects might also be due to a vasculopathy in NOTCH1-related AOS. Our results suggest that mutations in NOTCH1 are the most common cause of AOS and add to a growing list of human diseases that have a vascular and/or bony component and are caused by alterations in the Notch signaling pathway.

show abstract

mentioning

confidence: 73%

mentioning

confidence: 99%

Mutations in NOTCH1 Cause Adams-Oliver Syndrome

Stittrich

Lehman

Bodian

et al. 2014

The American Journal of Human Genetics

155

132

View full text Add to dashboard Cite

show abstract

“…It [Pouessel et al, 2006] Hepatoportal sclerosis +/+/À CMTC Gi-pt1 [Girard et al, 2005] Hepatoportal sclerosis +/+/Extra-hepatic portal vein obstruction CMTC Gi-pt2 [Girard et al, 2005] Hepatoportal sclerosis +/+/Extra-hepatic portal vein obstruction None known Sz-pt1 [Swartz et al, 1999] Hepatoportal sclerosis +/+/abnormal portal branches Extensive CMTC; lung plexigenic arteriopathy Shi-pt1 [Snape et al, 2009] Hepatoportal sclerosis +/?/? (unknown) Sp-pt2 [Snape et al, 2009] Fibrosis +/+/Absent & hypo-plastic portal branches CMTC Si-pt1 [Silva et al, 2012] Sinusoidal dilatation + /+/Hypoplastic portal branches; late obstruction CMTC; distal watershed stokes Fy-pt1 [Fayol et al, 2006] Massive steatosis À/À/À extensive CMTC; heart, kidney, brain (autopsy) Mee-pt5 first cousin [Meester et al, 2015] Fibrosis +/+/? None known…”

Section: Discussionmentioning

confidence: 99%

“…In 2014, mutations in NOTCH1 (MIM#190198) were identified in a father and daughter with AOS, three additional non-familial probands (one was previously described by Silva et al [2012]) and the proband from a fifth family previously described by Vandersteen and Dixon [2011] whose sister and father were not tested because they are no longer living [Stittrich et al, 2014]. Meester et al in 2015 screened 91 families with AOS and identified mutations in DLL4 (MIM#605185) in nine of those families [Meester et al, 2015].…”

Section: Introductionmentioning

confidence: 99%

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

Hassed

Mulvihill

et al. 2017

American J of Med Genetics Pt A

View full text Add to dashboard Cite

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.

show abstract

“…It is suggested that the disorder results from an early ontogenetic vascular abnormality. There is an association between the syndrome and portal hypertension due to hepatoportal sclerosis and extrahepatic portal vein obstruction, associated with nodular regenerative hyperplasia (Girard et al 2005;Silva et al 2012).…”

Section: Adams-oliver Syndromementioning

confidence: 99%

Tumor-Like Vascular Malformations

Zimmermann¹

2016

Tumors and Tumor-Like Lesions of the Hepatobiliary Tract

View full text Add to dashboard Cite

Vascular malformations represent a broad and complex spectrum of in part congenital and tumor-like conditions that occur either as systemic disorders or organ-specific pathologies. Hemodynamically, vascular malformations are classified as slow flow, high flow, and mixed malformations. The slow-flow disorders, Klippel-Trenaunay syndrome, Sturge-Weber syndrome, and unilateral nevoid telangiectatic syndrome, rarely involve the liver, where they manifest as abnormal vessels, mainly venous abnormalities, angiectases, and angioma-like lesions, sometimes associated with focal nodular hyperplasia or related changes. A distinct group of disorders is congenital and acquired venovenous malformations of the liver and patent ductus venosus, resulting in portosystemic shunts and associated parenchymal changes.

show abstract

Adams–Oliver syndrome and portal hypertension: Fortuitous association or common mechanism?

Cited by 4 publications

References 16 publications

Mutations in NOTCH1 Cause Adams-Oliver Syndrome

Mutations in NOTCH1 Cause Adams-Oliver Syndrome

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

Tumor-Like Vascular Malformations

Contact Info

Product

Resources

About