Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused byRASA1 mutations

作者：Nicole Revençu, Laurence Myriam Boon, John Butler Mulliken, Odile Enjolras, Maria Rosa Cordisco, Patricia E. Burrows, Philippe R. M. Clapuyt, Frank Hammer, Josée Dubois, Eulàlia Baselga, Francesco Brancati, Robin Carder, José Miguel Ceballos Quintal, Bruno Dallapiccola, Gayle O. Fischer, Ilona J. Frieden, María Camila Fontecha Garzón, John I Harper, Jennifer Johnson-Patel, Christine Labrèze, Loreto Martorell, Harriet J. Paltiel, Annette Pohl, Julie Prendiville, Isabelle Quéré, Dawn H. Siegel, Enza Maria Valente, Annet van Hagen, Liselot van Hest, Keith K. Vaux, Asunción Vicente, Lisa Weibel, David A. Chitayat, Miikka Vikkula · 发表于：Human Mutation · 年份：2008 · DOI：10.1002/humu.20746 · 被引用次数：437 · 研究领域：Vascular Malformations Diagnosis and Treatment、Vascular Malformations and Hemangiomas、Vascular Anomalies and Treatments

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.