z-logo
Premium
Diagnostic yield of genetic testing in epileptic encephalopathy in childhood
Author(s) -
MercimekMahmutoglu Saadet,
Patel Jaina,
Cordeiro Dawn,
Hewson Stacy,
Callen David,
Donner Elizabeth J.,
Hahn Cecil D.,
Kannu Peter,
Kobayashi Jeff,
Minassian Berge A.,
Moharir Mahendranath,
Siriwardena Komudi,
Weiss Shelly K.,
Weksberg Rosanna,
Snead O. Carter
Publication year - 2015
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12954
Subject(s) - epilepsy , encephalopathy , genetic testing , medicine , bioinformatics , pediatrics , genetics , biology , psychiatry
Summary Objective Epilepsy is a common neurologic disorder of childhood. To determine the genetic diagnostic yield in epileptic encephalopathy, we performed a retrospective cohort study in a single epilepsy genetics clinic. Methods We included all patients with intractable epilepsy, global developmental delay, and cognitive dysfunction seen between January 2012 and June 2014 in the Epilepsy Genetics Clinic. Electronic patient charts were reviewed for clinical features, neuroimaging, biochemical investigations, and molecular genetic investigations including targeted next‐generation sequencing of epileptic encephalopathy genes. Results Genetic causes were identified in 28% of the 110 patients: 7% had inherited metabolic disorders including pyridoxine dependent epilepsy caused by ALDH 7A1 mutation, Menkes disease, pyridox(am)ine‐5‐phosphate oxidase deficiency, cobalamin G deficiency, methylenetetrahydrofolate reductase deficiency, glucose transporter 1 deficiency, glycine encephalopathy, and pyruvate dehydrogenase complex deficiency; 21% had other genetic causes including genetic syndromes, pathogenic copy number variants on array comparative genomic hybridization, and epileptic encephalopathy related to mutations in the SCN 1A , SCN 2A , SCN 8A , KCNQ 2 , STXBP 1 , PCDH 19 , and SLC 9A6 genes. Forty‐five percent of patients obtained a genetic diagnosis by targeted next‐generation sequencing epileptic encephalopathy panels. It is notable that 4.5% of patients had a treatable inherited metabolic disease. Significance To the best of our knowledge, this is the first study to combine inherited metabolic disorders and other genetic causes of epileptic encephalopathy. Targeted next‐generation sequencing panels increased the genetic diagnostic yield from <10% to >25% in patients with epileptic encephalopathy.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here