Abstract
Cerebral cavernous malformations (CCM) are congenital vascular anomalies predominantly
of the central nervous system but may include lesions in other tissues such as the
retina, skin, and liver. These hamartomatous dysplasias, generally occurring sporadically,
consist of dynamic clustered convoluted capillary cavities without intervening brain
parenchyma that may lead to headaches, seizures, paresis, cerebral hemorrhages and
focal neurological deficits. Familial forms of CCM, inherited in an autosomal dominant
manner with incomplete penetrance and variable expression, are attributed to mutations
in three genes, CCM1, CCM2 and CCM3. Here, we report a kindred of Persian descent exhibiting a range of clinical symptoms
and features that include seizures, multiple lesions of the brain and spinal cord,
and severe hyperkeratotic cutaneous capillary–venous malformations. Sanger DNA sequencing
and deletion/duplication testing of the CCM1, CCM2, and CCM3 genes in the proband revealed a CCM1 c.601C>G mutation. Targeted mutation analysis in family members confirmed that this
mutation segregated with the disease in the family. This family illustrates the phenotypic
heterogeneity that has been observed in other reported CCM-pedigrees and highlights
the importance of genetic testing for early diagnosis in familial CCM. To our knowledge,
this is the first genetic investigation of CCM in the Persian population.
Keywords
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Article info
Publication history
Published online: September 05, 2013
Accepted:
July 29,
2013
Received in revised form:
July 17,
2013
Received:
September 13,
2012
Identification
Copyright
© 2013 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
