Clinicoradiologic data of familial cerebral cavernous malformation with age‐related disease burden

Abstract

Abstract Objective Familial cerebral cavernous malformation (FCCM) is an autosomal dominant disease induced by loss‐of‐function mutations in three CCM genes, KRIT1, CCM2, and PDCD10. However, previous studies paid little attention to analyzing the radiologic features and age‐related disease burden according to the genes. Therefore, we retrospectively reviewed the genetic tests of our center's clinical FCCM patients. Method This study investigated clinical FCCM patients with multiple lesions or a family history of CCMs who underwent the FCCM gene (KRTI1, CCM2, and PDCD10) panel test. The clinical, genetic, and radiologic features were analyzed. Result Among the patients (n = 34) undergoing the FCCM gene test, twenty‐seven patients had CCM confirmed by brain MRI, and twenty‐one patients were considered to have FCCM (cohort 1). In cohort 1, thirteen patients had mutations in the FCCM gene, but eight did not. Cohort 2 comprised cohort 1 and four family members with the same mutation as the probands. Six novel variants in CCM genes were detected (KRIT1 c.22_26del, c.815dup, c.1094_1098del, c.1147‐2A>G, c.2124dup, and PDCD10 c.150 + 1dup). Cohort 1 demonstrated that brainstem lesions were mostly associated with the mutation detection in CCM genes (brainstem, lateral temporal, and parietal lesions vs. lateral temporal and parietal lesions, AUC 0.928 vs. 0.779, P = 0.0389). The radiologic severity worsened according to age in the KRIT1 group compared with the Mutation not detected group (correlation coefficient 0.75 (P < 0.001) versus 0.53 (P = 0.004)). Conclusion The brainstem lesion could be the radiologic marker for FCCM with the mutation detected. The age‐related disease burden regarding FCCM according to genetic information was demonstrated.