Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused by RASA1 mutations. Hum Mutat 2008 Jul;29(7):959-65
Date
05/01/2008Pubmed ID
18446851DOI
10.1002/humu.20746Scopus ID
2-s2.0-46749101035 (requires institutional sign-in at Scopus site) 334 CitationsAbstract
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.
Author List
Revencu N, Boon LM, Mulliken JB, Enjolras O, Cordisco MR, Burrows PE, Clapuyt P, Hammer F, Dubois J, Baselga E, Brancati F, Carder R, Quintal JM, Dallapiccola B, Fischer G, Frieden IJ, Garzon M, Harper J, Johnson-Patel J, Labrèze C, Martorell L, Paltiel HJ, Pohl A, Prendiville J, Quere I, Siegel DH, Valente EM, Van Hagen A, Van Hest L, Vaux KK, Vicente A, Weibel L, Chitayat D, Vikkula MMESH terms used to index this publication - Major topics in bold
Arteriovenous MalformationsFamily
Humans
Immunoglobulin Variable Region
Mutation
Phenotype
Recombinant Proteins
Single-Chain Antibodies
Syndrome
Vascular Malformations
Vein of Galen Malformations
p120 GTPase Activating Protein