DOI: 10.5061/dryad.w0vt4b8qr
title: Clinical and genetic features in patients with reflex bathing epilepsy

description: 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.
description: <b>Study
 design and participant recruitment</b> We enrolled 12 previously unreported probands from 10 unrelated families (Figure 1A) with reflex epilepsy induced by showering or bathing through the network therapy of rare epilepsies (NETRE). Inclusion criteria were patients with bathing/showering induced seizures documented either via video-EEG or home-video recordings by the parents. After ethical approval from the IRCCS ‘G. Gaslini’ Institute (Genova, Italy), clinical data including genetic findings, neurodevelopmental performance, epilepsy phenotype, and treatment response were collected using an anonymized, electronic questionnaire. Interictal/ictal (video)-EEG recordings, brain MRI, and neuropsychological tests were centrally reviewed. The neuropsychological and behavioral evaluation was assessed by the Wechsler Intelligence Scale for Children-IV (WISC-IV), Wechsler Preschool and Primary Scale of Intelligence-III (WPPSI-III), Autism Diagnostic Observation Schedule (ADOS), and Griffiths Mental Development Scale- Extended Revised (GMDS-ER). Individualized patient consent was taken and retained by the local clinicians. <b>Genetic investigations</b> Genomic DNA was isolated from leukocytes of peripheral blood by using standard protocols. Target genetic analysis of <i>SYN1</i> was performed by Sanger sequencing in subjects of families 1-4, 7, 8. Other subjects were investigated either by epilepsy gene panels (family 6, 10) or whole-exome sequencing (WES) (families 5, 9) and identified variants were confirmed by Sanger sequencing (additional details about sequencing process and data analysis are available in Supplemental Data). Variants were classified according to the ACMG guidelines<sup>21</sup>. In parallel, we screened for SYN1 mutations in a previously reported<sup>10</sup> cohort of 21 HWE patients to gain further insights into genotype-phenotype correlations of water-related reflex epilepsies.
description: These supplemental files include an extensive clinical
 description of affected patients, methods of genetic testing, EEG finidngs
 and several video showing typical presentation of reflex bathing
 epilepsy.