Clinical and genetic features in patients with reflex bathing epilepsy
Accogli, Andrea; Striano, Pasquale (2021), Clinical and genetic features in patients with reflex bathing epilepsy, Dryad, Dataset, https://doi.org/10.5061/dryad.w0vt4b8qr
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.
Study design and participant recruitment
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.
Genomic DNA was isolated from leukocytes of peripheral blood by using standard protocols. Target genetic analysis of SYN1 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 guidelines21. In parallel, we screened for SYN1 mutations in a previously reported10 cohort of 21 HWE patients to gain further insights into genotype-phenotype correlations of water-related reflex epilepsies.
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.