A whole genome sequencing (WGS) study has been carried out across the Canadian Epilepsy Network development and epileptic encephalopathy (DEE) cohort.4 To be included in the study patients were required to have intractable epilepsy (treatment failure with 2 appropriate and well-tolerated antiseizure medications over a 6-month period), and an average of at least one focal, generalized tonic‒clonic, myoclonic, tonic, atonic or absence seizure, or epileptic spasm per month, development delay, no structural malformations (on imaging), and no family history of epilepsy.4 WGS was conducted on 197 participants with DEE and their unaffected parents.4 A molecular diagnosis was achieved in 63 participants, 53 of whom had de novo mutations, and 4 who had de novo CNVs.4
References:
1. Krey I, Platzer K, Esterhuizen A, et al. Current practice in diagnostic genetic testing of the epilepsies. Epileptic Disord 2022; 24 (5): 765‒786.
2. Grinton BE, Heron SE, Pelekanos JT, et al. Familial neonatal seizures in 36 families: Clinical and genetic features correlate with outcome. Epilepsia 2015; 56 (7): 1071‒1080.
3. Vadlamudi L, Milne RL, Lawrence K, et al. Genetics of epilepsy: the testimony of twins in the molecular era. Neurology 2014; 83 (12): 1042‒1048.
4. Hamdan FF, Myers CT, Cossette P, et al. High rate of recurrent de novo mutations in developmental and epileptic encephalopathies. Am J Hum Genet 2017; 101 (5): 664‒685.
5. McTague A, Howell KB, Cross JH, et al. The genetic landscape of the epileptic encephalopathies of infancy and childhood. Lancet Neurol 2016; 15 (3): 304‒316.
6. Cvetkovska E, Kuzmanovski I, Babunovska M, et al. Phenotypic spectrum in families with mesial temporal lobe epilepsy probands. Seizure 2018; 58: 13‒16.