SYN1 Mutation Causes X-Linked Toothbrushing Epilepsy in a Chinese Family

Toothbrushing epilepsy is a rare form of reflex epilepsy (RE) with sporadic incidence. To characterize the genetic profile of reflex epilepsy patients with tooth brushing-induced seizures in a Chinese family. Solo clinical whole-exome sequencing (WES) of the proband, a 37-year-old Chinese man, was performed to characterize the genetic etiology of toothbrushing epilepsy. Mutations in the maternal X-linked synapsin 1 (SYN1) identified in the proband and his family members were confirmed by Sanger sequencing. The pathogenicity of these mutations was determined using in silico analysis. The proband had four episodes of toothbrushing-induced seizures. The semiology included nausea, twitching of the right side of the mouth and face, followed by a generalized tonic-clonic seizure (GTCS). The proband's elder maternal uncle had three toothbrushing-induced epileptic seizures at the age of 26. The proband's younger maternal uncle had no history of epileptic seizures but had a learning disability and aggressive tendencies. We identified a deleterious nonsense mutation, c.1807C>T (p.Q603Ter), in exon 12 of the SYN1 gene (NM_006950), which can result in a truncated SYN1 phosphoprotein with altered flexibility and hydropathicity. This novel mutation has not been reported in the 1000G, EVS, ExAC, gnomAD, or HGMD databases. We identified a novel X-linked SYN1 exon 12 mutant gene in a Chinese family with toothbrushing epilepsy. Our findings provide novel insights into the mechanism of this complex form of reflex epilepsy that could potentially be applied in disease diagnosis.

Symptomatic eating epilepsy: two novel pediatric patients and review of literature

Eating epilepsy (EE) is a form of reflex epilepsy in which seizures are triggered by eating. It is a rare condition but a high prevalence has been reported in Sri Lanka. In EE, the ictal semiology includes focal seizures with or without secondary generalization or generalized seizures. Some cases are idiopathic while focal structural changes on imaging, if present, are often confined to the temporal lobe or perisylvian region. On the other hand, some cases support the hypothesis of a genetic aetiology. The prognosis of EE is extremely variable due to the different nature of the underlying disorder. We describe two patients with symptomatic eating epilepsy, a 13-year-old boy with a bilateral perisylvian polymicrogyria and a 2-year-old boy with a genetic cause. The presence of structural lesions or the dysfunction of specific cortical regions in the context of a germline genetic alteration might lead to a hyperexcitation fostering the epileptogenesis. We review the available literature to clarify the aetiopathogenesis and the mechanisms underlying EE to improve the diagnosis and the management of these rare conditions.

Clinical and Genetic Features in Patients With Reflex Bathing Epilepsy

Objective:To describe the clinical and genetic findings in a cohort of subjects with bathing epilepsy, a rare form of reflex epilepsy.Methods:We investigated by Sanger and targeted re-sequencing the SYN1 gene in 12 individuals from 10 different families presenting with seizures primarily triggered by bathing or showering. Additional twelve subjects with hot-water epilepsy were also screened.Results:In all families with bathing epilepsy we identified 8 distinct pathogenic or likely pathogenic variants and 2 variants of unknown significance in SYN1, nine of which are novel. Conversely, none of the subjects with hot-water epilepsy displayed SYN1 variants. In mutated subjects, seizures were typically triggered by showering or bathing regardless of the water temperature. Additional triggers included fingernail-clipping, hair-cutting, or watching someone take a shower. Non-provoked seizures and a variable degree of developmental delay were also common.Conclusion:bathing epilepsy is genetically distinct reflex epilepsy mainly caused by SYN1 mutations.