PT  - JOURNAL ARTICLE
AU  - Li, Chunwang
AU  - Zhuo, Lingyun
AU  - Kang, Yaqing
AU  - Liu, Penghui
AU  - Huang, Weilin
AU  - Li, Qixuan
AU  - Ma, Ke
AU  - Huang, Shuna
AU  - Lin, Xinru
AU  - Zhuang, Weiheng
AU  - Wang, Haojie
AU  - Chen, Darong
AU  - Wang, Huimin
AU  - He, Qiu
AU  - Gao, Zhuyu
AU  - Niu, Xuegang
AU  - Jing, Yajun
AU  - Yan, Lingjun
AU  - Gao, Bin
AU  - Wang, Dengliang
AU  - Lin, Shaowei
AU  - Wu, Siying
AU  - Lin, Yuanxiang
AU  - Kang, Dezhi
AU  - Lin, Fuxin
TI  - Prevalence, genetic and clinical characteristics in first-degree relatives of patients with familial cerebral cavernous malformations in China
AID  - 10.1136/svn-2023-003004
DP  - 2025 Feb 01
TA  - Stroke and Vascular Neurology
PG  - 45--54
VI  - 10
IP  - 1
4099  - http://svn.bmj.com/content/10/1/45.short
4100  - http://svn.bmj.com/content/10/1/45.full
SO  - Stroke Vasc Neurol2025 Feb 01; 10
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.