RT Journal Article
SR Electronic
T1 Prevalence, genetic and clinical characteristics in first-degree relatives of patients with familial cerebral cavernous malformations in China
JF Stroke and Vascular Neurology
JO Stroke Vasc Neurol
FD BMJ Publishing Group Ltd
SP 45
OP 54
DO 10.1136/svn-2023-003004
VO 10
IS 1
A1 Li, Chunwang
A1 Zhuo, Lingyun
A1 Kang, Yaqing
A1 Liu, Penghui
A1 Huang, Weilin
A1 Li, Qixuan
A1 Ma, Ke
A1 Huang, Shuna
A1 Lin, Xinru
A1 Zhuang, Weiheng
A1 Wang, Haojie
A1 Chen, Darong
A1 Wang, Huimin
A1 He, Qiu
A1 Gao, Zhuyu
A1 Niu, Xuegang
A1 Jing, Yajun
A1 Yan, Lingjun
A1 Gao, Bin
A1 Wang, Dengliang
A1 Lin, Shaowei
A1 Wu, Siying
A1 Lin, Yuanxiang
A1 Kang, Dezhi
A1 Lin, Fuxin
YR 2025
UL http://svn.bmj.com/content/10/1/45.abstract
AB Objective This study aims to investigate the prevalence of familial cerebral cavernous malformations (FCCMs) in first-degree relatives (FDRs) using familial screening, to describe the distribution of initial symptoms, lesion count on cranial MRI and pathogenic gene in patients.Methods Patients with multiple CCMs who enrolled from the Treatments and Outcomes of Untreated Cerebral Cavernous Malformations in China database were considered as probands and FDRs were recruited. Cranial MRI was performed to screen the CCMs lesions, and whole-exome sequencing was performed to identify CCM mutations. MRI and genetic screening were combined to diagnose FCCM in FDRs, and the results were presented as prevalence and 95% CIs. The Kaplan-Meier (KM) method was used to calculate the cumulative incidence of FCCM.Results 33 (76.74%) of the 43 families (110 FDRs) were identified as FCCM (85 FDRs). Receiver operating characteristic analysis revealed three lesions on T2-weighted imaging (T2WI) were the strong indicator for distinguishing probands with FCCM (sensitivity, 87.10%; specificity, 87.50%). Of the 85 FDRs, 31 were diagnosed with FCCM, resulting in a prevalence of 36.5% (26.2%–46.7%). In families with FCCMs, the mutation rates for CCM1, CCM2 and CCM3 were 45.45%, 21.21% and 9.09%, respectively. Furthermore, 53.13% of patients were asymptomatic, 17.19% were intracranial haemorrhage and 9.38% were epilepsy. The mean age of symptom onset analysed by KM was 46.67 (40.56–52.78) years.Conclusion Based on MRI and genetic analysis, the prevalence of CCMs in the FDRs of families with FCCMs in China was 36.5%. Genetic counselling and MRI screening are recommended for FDRs in patients with more than three CCM lesions on T2WI.Data are available on reasonable request.