Cutaneous venous malformations in familial cerebral cavernomatosis caused by KRIT1 gene mutations.

BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular lesions characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. Although often asymptomatic, seizures, cerebral haemorrhages and focal neurological deficits are well-documented complications. Mutations in the CCM1 (7q21-22), CCM2 (7p13-15) and CCM3 (3q25.2-27) genes have been identified in familial CCM. In rare instances, the association of congenital hyperkeratotic cutaneous capillary-venous malformations (HCCVMs) with CCM1 has been reported. OBSERVATIONS: We studied 6 members of a family with CCMs. Four members of the family developed late-onset multiple, tiny, bluish, soft, cutaneous papules, mainly located on the face, arm and abdominal area, corresponding histologically to venous malformations. A splice donor site mutation in intron 4 (c. 1146 + 1 G-->A) in the CCM1 gene was identified. CONCLUSIONS: Our findings suggest that mutations in the KRIT1 gene may cause phenotypically heterogeneous cutaneous vascular lesions other than those previously described as HCCVMs.