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Cerebral cavernous malformations: clinical insights from genetic studies.
- Source :
-
Neurosurgical focus [Neurosurg Focus] 2006 Jul 15; Vol. 21 (1), pp. e1. Date of Electronic Publication: 2006 Jul 15. - Publication Year :
- 2006
-
Abstract
- Familial disease is responsible for one third to one half of cerebral cavernous malformation (CCM) cases presenting to clinical attention. Much has been learned in the past decade about the genetics of these cases, which are all inherited in an autosomal dominant pattern, at three known chromosome loci. Unique features of inherited CCMs in Hispanic-Americans of Mexican descent have been described. The respective genes for each locus have been identified and preliminary observations on disease pathways and mechanisms are coming to light, including possible explanations for selectivity of neural milieu and relationships to endothelial layer abnormalities. Mechanisms of lesion genesis in cases of genetic predisposition are being investigated, with evidence to support a two-hit model emerging from somatic mutation screening of the lesions themselves and from lesion formation in transgenic murine models of the disease. Other information on potential inflammatory factors has emerged from differential gene expression studies. Unique phenotypic features of solitary versus familial cases have emerged: different associations with venous developmental anomaly and the exceptionally high penetrance rates that are found in inherited cases when high-sensitivity screening is performed with gradient echo magnetic resonance imaging. This information has changed the landscape of screening and counseling for patients and their families, and promises to lead to the development of new tools for predicting, explaining, and modifying disease behavior.
- Subjects :
- Animals
Brain Neoplasms diagnosis
Brain Neoplasms physiopathology
Cerebral Veins abnormalities
Cerebral Veins pathology
Cerebral Veins physiopathology
Disease Models, Animal
Hemangioma, Cavernous, Central Nervous System diagnosis
Hemangioma, Cavernous, Central Nervous System physiopathology
Hispanic or Latino genetics
Humans
Inheritance Patterns genetics
Mice
Brain Neoplasms genetics
Genetic Predisposition to Disease
Hemangioma, Cavernous, Central Nervous System genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1092-0684
- Volume :
- 21
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neurosurgical focus
- Publication Type :
- Academic Journal
- Accession number :
- 16859247
- Full Text :
- https://doi.org/10.3171/foc.2006.21.1.2