MED23-associated refractory epilepsy successfully treated with the ketogenic diet.
We report a new patient with refractory epilepsy associated with a novel pathogenic homozygous MED23 variant. This 7.5-year-old boy from consanguineous parents had infantile onset global developmental delay and refractory epilepsy. He was treated with the ketogenic diet at 2.5 years of age and became seizure free on the first day. He had microcephaly and truncal hypotonia. His brain MRI showed delayed myelination and thin corpus callosum. He was enrolled in a whole exome sequencing research study, which identified a novel, homozygous, likely pathogenic (c.1937A>G; p.Gln646Arg) variant in MED23. MED23 is a regulator of energy homeostasis and glucose production. Liver-specific Med23-knockout mice showed reduced liver gluconeogenesis and lower blood glucose levels compared to control mice. This is the first patient with documented refractory epilepsy caused by a novel homozygous pathogenic variant in MED23 expanding the phenotypic spectrum. Identification of the underlying genetic defect in MED23 sheds light on the possible mechanism of complete response to the ketogenic diet in this child. © 2016 Wiley Periodicals, Inc.
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada.
Anath C
AC
Lionel
Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Nasim
N
Monfared
Department of Molecular Genetics and the McLaughlin Centre, University of Toronto, Toronto, Canada.|Genetics and Genome Biology Research Program, Research Institute, The Hospital for Sick Children, Toronto, Canada.
Stephen W
SW
Scherer
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada.
Christian R
CR
Marshall
Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.|Genetics and Genome Biology Research Program, Research Institute, The Hospital for Sick Children, Toronto, Canada.
Saadet
S
Mercimek-Mahmutoglu
D000483:Alleles; D001921:Brain / Q000473:pathology; D002648:Child; D055423:Diet, Ketogenic; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis / Q000178:diet therapy* / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D056892:Mediator Complex / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D016896:Treatment Outcome
C492159:MED23 protein, human; D056892:Mediator Complex
MED23; intellectual disability; ketogenic diet; refractory epilepsy