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Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused by RASA1 mutations

✍ Scribed by Nicole Revencu; Laurence M. Boon; John B. Mulliken; Odile Enjolras; Maria Rosa Cordisco; Patricia E. Burrows; Philippe Clapuyt; Frank Hammer; Josée Dubois; Eulalia Baselga; Francesco Brancati; Robin Carder; José Miguel Ceballos Quintal; Bruno Dallapiccola; Gayle Fischer; Ilona J. Frieden; Maria Garzon; John Harper; Jennifer Johnson-Patel; Christine Labrèze; Loreto Martorell; Harriet J. Paltiel; Annette Pohl; Julie Prendiville; Isabelle Quere; Dawn H. Siegel; Enza Maria Valente; Annet Van Hagen; Liselot Van Hest; Keith K. Vaux; Asuncion Vicente; Lisa Weibel; David Chitayat; Miikka Vikkula


Book ID
102262106
Publisher
John Wiley and Sons
Year
2008
Tongue
English
Weight
260 KB
Volume
29
Category
Article
ISSN
1059-7794

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✦ Synopsis


Communicated by Peter Byers

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