Human Molecular Genetics Advance Access originally published online on July 31, 2007
Human Molecular Genetics 2007 16(R2):R140-R149; doi:10.1093/hmg/ddm211
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Genetic causes of vascular malformations
Laboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels B-1200, Belgium
* To whom correspondence should be addressed at: Laboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 74, BP 75.39, Brussels B-1200, Belgium. Tel: +32 27647496; Fax: +32 27647460; Email: miikka.vikkula{at}uclouvain.be
Received July 11, 2007; Accepted July 26, 2007
Vascular malformations are localized defects of vascular development. They usually affect a limited number of vessels in a restricted area of the body. Although most malformations are sporadic, inheritance is observed, enabling genetic analysis. Usually, sporadic forms present with a single lesion whereas multiple lesions are observed in familial cases. The last decade has seen unraveling of several causative genes and beginning of elucidation of the pathophysiological pathways involved in the inherited forms. In parallel, definition of the clinical phenotypes has improved and disorders such as Parkes-Weber syndrome (PKWS), first thought to be sporadic, is now known to be part of a more common inheritable phenotype. In addition, the concept of double-hit mechanism that we proposed earlier to explain the incomplete penetrance, variable expressivity and multifocality of lesions in inherited venous anomalies is now becoming confirmed, as some somatic mutations have been identified in venous, glomuvenous and cerebral cavernous malformations. It is thus tempting to suggest that familial forms of vascular malformations follow paradominant inheritance and that sporadic forms, the etiopathogenic causes of which are still unelucidated, are caused by somatic mutations in the same genes.