GENETICS OF CEREBRAL CAVERNOUS MALFORMATIONS: IDENTIFICATION OF RESPONSIBLE GENES

Cerebral Cavernous Malformations are vascular malformations, mostly located in the central nervous system, with a prevalence of 0.1-0.5% in the general population. These lesions are characterized by abnormally enlarged and leaky capillary cavities (caverns) lined by a thin endothelium layer ranging in size from a few millimeters to a few centimeters. They can be either clinically silent or give rise to clinical symptoms ranging from headaches and focal neurological deficits to seizures and fatal intracerebral hemorrhage. Identification of these lesions is important because surgical removal of many is possible and necessary for patients with recurrent hemorrhage or intractable seizures. Magnetic resonance imaging (MRI) is the diagnostic modality of choice and symptomatic disease typically begins in the third-fifth decades of life, although lesions have been described in all age groups. The past few years have seen rapid advances in our understanding of the genetics of Cerebral Cavernous Malformations with the identification of three causative genes. Objective of this proposal is the identification of additional causative genes responsible for Cerebral Cavernous Malformations. Our proposed research can help to better understand the molecular mechanisms underlying pathogenesis and to develop therapeutic methods.