CADASIL type 1 with cysteine-sparing P572L mutation on exon 11 presenting as focal onset epilepsy: a case report

Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small-vessel disease, typically with adult-onset. It is most often caused by NOTCH3 mutations that involve cysteine residues. Cases of CADASIL type 1 with cysteine-sparing mutations presenting with seizures are rarely reported. Case presentation A 66-year-old Chinese Han woman was admitted for two episodes of focal to bilateral tonic-clonic seizures, as documented by interictal video electroencephalogram (VEEG). Brain magnetic resonance imaging (MRI) showed severe white matter hyperintensity (WMH) sparing the temporal lobes and lacunar infarcts in the basal ganglia. She had a 31-year history of cognitive impairment, a 26-year history of headaches, and a six-month history of gait disturbance. Whole exome sequencing (WES) identified a heterozygous NOTCH3 c.1715 C > T (p. Pro572Leu) mutation on exon 11, which, despite being a variant of uncertain significance (VUS) in ClinVar, is suggested to be pathogenic by in silico tools and family co-segregation, supporting the diagnosis of CADASIL type 1. Her affected son carried the same mutation, while her two daughters did not. The proband improved with valproate, aspirin, atorvastatin, and donepezil. Conclusions This report is the first to comprehensively describe a CADASIL type 1 patient with cysteine-sparing Pro572Leu mutation presenting with focal to bilateral tonic-clonic seizures.