Description of Two Families with New Mutations in Familial Cerebral Cavernous Malformations Genes

Cerebral cavernous malformations (CCMs) are dilated aberrant leaky capillaries located in the Central Nervous System. Familial CCM is an autosomal dominant inherited disorder related to mutations in KRIT1, Malcavernin or PDCD10. We show two unrelated families presenting familial CCM due to two new mutations in KRIT1 and PDCD10, producing truncated proteins. Clinical phenotype was highly variable among patients from asymptomatic individuals to diplopia, seizures or severe intracranial hemorrhage. PDCD10 patients usually show a more aggressive course and they frequently showed multiple meningiomas. This work provides evidence for the pathogenicity of two new mutations in CCM genes and supports previous findings regarding familial CCM and multiple meningiomas.

Automated summary

Familial CCM is an autosomal dominant inherited disorder related to mutations in KRIT1, Malcavernin or PDCD10, with clinical phenotype ranging from asymptomatic individuals to severe intracranial hemorrhage. Patients with PDCD10 mutations often exhibit a more aggressive course and frequently show multiple meningiomas. This study provides evidence for the pathogenicity of new mutations in CCM genes and supports previous findings on familial CCM and multiple meningiomas.