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Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast‐flow vascular anomalies are caused by RASA1 mutations
Author(s) -
Revencu Nicole,
Boon Laurence M.,
Mulliken John B.,
Enjolras Odile,
Cordisco Maria Rosa,
Burrows Patricia E.,
Clapuyt Philippe,
Hammer Frank,
Dubois Josée,
Baselga Eulalia,
Brancati Francesco,
Carder Robin,
Quintal José Miguel Ceballos,
Dallapiccola Bruno,
Fischer Gayle,
Frieden Ilona J.,
Garzon Maria,
Harper John,
JohnsonPatel Jennifer,
Labrèze Christine,
Martorell Loreto,
Paltiel Harriet J.,
Pohl Annette,
Prendiville Julie,
Quere Isabelle,
Siegel Dawn H.,
Valente Enza Maria,
Van Hagen Annet,
Van Hest Liselot,
Vaux Keith K.,
Vicente Asuncion,
Weibel Lisa,
Chitayat David,
Vikkula Miikka
Publication year - 2008
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20746
Subject(s) - arteriovenous malformation , biology , sturge–weber syndrome , pten , penetrance , vascular malformation , macrocephaly , phenotype , intracranial arteriovenous malformations , pathology , haploinsufficiency , angiomatosis , neurofibromatosis , genetics , medicine , cerebral angiography , gene , dermatology , radiology , angiography , apoptosis , pi3k/akt/mtor pathway
Capillary malformation‐arteriovenous malformation (CM‐AVM) is a newly recognized autosomal dominant disorder, caused by mutations in the RASA1 gene in six families. Here we report 42 novel RASA1 mutations and the associated phenotype in 44 families. The penetrance and de novo occurrence were high. All affected individuals presented multifocal capillary malformations (CMs), which represent the hallmark of the disorder. Importantly, one‐third had fast‐flow vascular lesions. Among them, we observed severe intracranial AVMs, including vein of Galen aneurysmal malformation, which were symptomatic at birth or during infancy, extracranial AVM of the face and extremities, and Parkes Weber syndrome (PKWS), previously considered sporadic and nongenetic. These fast‐flow lesions can be differed from the other two genetic AVMs seen in hereditary hemorrhagic telangiectasia (HHT) and in phosphatase and tensin homolog (PTEN) hamartomatous tumor syndrome. Finally, some CM‐AVM patients had neural tumors reminiscent of neurofibromatosis type 1 or 2. This is the first extensive study on the phenotypes associated with RASA1 mutations, and unravels their wide heterogeneity. Hum Mutat 29(7), 959–965, 2008. © 2008 Wiley‐Liss, Inc.