Cerebral cavernous malformation: new molecular and clinical insights

Nicole Revencu ¹ and Miikka Vikkula ^2*

¹ Institute of Cellular Pathology, Belgium
² Laboratory of Human Molecular Genetics, Belgium

^* To whom correspondence should be addressed. E-mail: vikkula{at}bchm.ucl.ac.be.

Accepted 9 March 2006

Abstract

Cerebral cavernous malformation (CCM) is a vascular malformation causing neurological problems, such as headaches, seizures, focal neurological deficits and cerebral haemorrhages. CCMs can occur sporadically or as an autosomal dominant condition with variable expression and incomplete penetrance. Familial forms have been linked to three chromosomal loci and loss-of-function mutations have been identified in the KRIT1/CCM1, the MGC4607/CCM2 and the PDCD10/CCM3 genes. Recently, many new pieces of data have been added to the CCM puzzle. It has been shown that the three CCM genes are rather expressed in neurons than in blood vessels. The interaction between CCM1 and CCM2, which was expected on the basis of their structure, has also been proven suggesting a common functional pathway. Finally, in a large series of KRIT1 mutation carriers, clinical and neuroradiological features have been characterized. This data should lead to more appropriate follow-up, treatment and genetic counselling. The recent developments will also help to elucidate the precise pathogenetic mechanisms leading to CCM, contributing to a better understanding of normal and pathological angiogenesis, and finally, to the development of targeted therapies.

Keywords: CCM, angiogenesis, cerebral cavernous malformation, vascular malformation

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