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.


METHODS
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.
Toll
Agustí
A
Department of Dermatology, Hospital del Mar, IMAS, Barcelona ES-08003, Spain. 93828@imas.imim.es
Parera
Elisabet
E
Giménez-Arnau
Ana M
AM
Pou
Alejandro
A
Lloreta
Josep
J
Limaye
Nisha
N
Vikkula
Miikka
M
Pujol
Ramon M
RM
D000328:Adult; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000150:complications / Q000235:genetics*; D020785:Central Nervous System Vascular Malformations / Q000150:complications / Q000235:genetics*; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000150:complications / Q000235:genetics*; D006801:Humans; D000075927:KRIT1 Protein; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017445:Skin Diseases, Vascular / Q000150:complications / Q000235:genetics* / Q000473:pathology; D054079:Vascular Malformations / Q000150:complications / Q000235:genetics* / Q000473:pathology; D014680:Veins / Q000002:abnormalities
D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins