Familial Cerebral Cavernous Malformations : A Clinical Series and Literature Review

Abstract

Objective: Familial cerebral cavernous malformation (FCCM) is a genetically inherited condition involving the collection of abnormal slow-flow venous capillaries with no cerebral parenchyma in between. In this case series, we review the clinical, radiological, pathological, and genetic findings of seven blood relatives diagnosed with FCCM and discuss their treatment in light of the different presentations.

Methods: The patients with FCCMs were assessed in our neurosurgery clinic between April 2016 and October 2024. All patients underwent detailed clinical evaluation, radiological imaging, histopathological examination, and genetic testing. Functional outcomes were evaluated using the Karnofsky performance scale (KPS).

Results: Five of the seven patients were symptomatic, while the remaining two were asymptomatic carriers. On radiological examination, hemorrhagic type I lesions were detected in symptomatic cases, whereas the asymptomatic carriers had non-hemorrhagic type 4 lesions. Genetic testing revealed a heterozygous pathogenic mutation in the CCM1 gene in one of the symptomatic patients. The three symptomatic cases underwent surgery for complete resection of the lesions; no additional neurological deficit or residual lesion was detected postoperatively (postoperative KPS score, 100). Histopathological examination revealed benign cavernous angioma in all cases. Over the postoperative follow-up, no seizures were detected in patients who underwent surgery due to refractory epilepsy.

Conclusion: Advances in molecular genetic testing have allowed for prompt diagnosis and timely management of patients with FCCMs. Surgical treatment is an effective option in symptomatic cases with progressive neurological deficits and refractory epilepsy. Regular neurological monitoring and radiological assessment are recommended in symptomatic cases and asymptomatic carriers.

Keywords: Cerebral cavernous malformation; Cerebral cavernous malformations 1 protein; Family characteristics.