TY - JOUR
T1 - Diagnostic yield of genetic testing in epileptic encephalopathy in childhood
AU - Mercimek-Mahmutoglu, Saadet
AU - Patel, Jaina
AU - Cordeiro, Dawn
AU - Hewson, Stacy
AU - Callen, David
AU - Donner, Elizabeth J.
AU - Hahn, Cecil D.
AU - Kannu, Peter
AU - Kobayashi, Jeff
AU - Minassian, Berge A.
AU - Moharir, Mahendranath
AU - Siriwardena, Komudi
AU - Weiss, Shelly K.
AU - Weksberg, Rosanna
AU - Snead, O. Carter
N1 - Publisher Copyright:
© Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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 ALDH7A1 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 SCN1A, SCN2A, SCN8A, KCNQ2, STXBP1, PCDH19, and SLC9A6 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.
AB - 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 ALDH7A1 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 SCN1A, SCN2A, SCN8A, KCNQ2, STXBP1, PCDH19, and SLC9A6 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.
KW - Chromosomal
KW - Epilepsy
KW - Genetics
KW - Metabolic disorders
KW - Molecular genetics
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U2 - 10.1111/epi.12954
DO - 10.1111/epi.12954
M3 - Article
C2 - 25818041
AN - SCOPUS:84929510832
SN - 0013-9580
VL - 56
SP - 707
EP - 716
JO - Epilepsia
JF - Epilepsia
IS - 5
ER -