INTRODUCTION: CDKL5-related encephalopathy is an X-linked dominantly inherited disorder that is characterized by early infantile epileptic encephalopathy or atypical Rett syndrome. We describe a 5-year-old Japanese boy with intractable epilepsy, severe developmental delay, and Rett syndrome-like features. Onset was at 2 months, when his electroencephalogram showed sporadic single poly spikes and diffuse irregular poly spikes. METHODS: We conducted a genetic analysis using an Illumina® TruSight™ One sequencing panel on a next-generation sequencer. RESULTS: We identified two epilepsy-associated single nucleotide variants in our case: CDKL5 p.Ala40Val and KCNQ2 p.Glu515Asp. CDKL5 p.Ala40Val has been previously reported to be responsible for early infantile epileptic encephalopathy. In our case, the CDKL5 heterozygous mutation showed somatic mosaicism because the boy's karyotype was 46,XY. The KCNQ2 variant p.Glu515Asp is known to cause benign familial neonatal seizures-1, and this variant showed paternal inheritance. CONCLUSIONS: Although we believe that the somatic mosaic CDKL5 mutation is mainly responsible for the neurological phenotype in the patient, the KCNQ2 variant might have some neurological effect. Genetic analysis by next-generation sequencing is capable of identifying multiple variants in a patient.
INTRODUCTION:CDKL5-related encephalopathy is an X-linked dominantly inherited disorder that is characterized by early infantile epilepticencephalopathy or atypical Rett syndrome. We describe a 5-year-old Japanese boy with intractable epilepsy, severe developmental delay, and Rett syndrome-like features. Onset was at 2 months, when his electroencephalogram showed sporadic single poly spikes and diffuse irregular poly spikes. METHODS: We conducted a genetic analysis using an Illumina® TruSight™ One sequencing panel on a next-generation sequencer. RESULTS: We identified two epilepsy-associated single nucleotide variants in our case: CDKL5p.Ala40Val and KCNQ2p.Glu515Asp. CDKL5p.Ala40Val has been previously reported to be responsible for early infantile epilepticencephalopathy. In our case, the CDKL5 heterozygous mutation showed somatic mosaicism because the boy's karyotype was 46,XY. The KCNQ2 variant p.Glu515Asp is known to cause benign familial neonatal seizures-1, and this variant showed paternal inheritance. CONCLUSIONS: Although we believe that the somatic mosaic CDKL5 mutation is mainly responsible for the neurological phenotype in the patient, the KCNQ2 variant might have some neurological effect. Genetic analysis by next-generation sequencing is capable of identifying multiple variants in a patient.
Authors: Heather E Olson; Scott T Demarest; Elia M Pestana-Knight; Lindsay C Swanson; Sumaiya Iqbal; Dennis Lal; Helen Leonard; J Helen Cross; Orrin Devinsky; Tim A Benke Journal: Pediatr Neurol Date: 2019-02-23 Impact factor: 3.372
Authors: Sam Amin; Marie Monaghan; Angel Aledo-Serrano; Nadia Bahi-Buisson; Richard F Chin; Angus J Clarke; J Helen Cross; Scott Demarest; Orrin Devinsky; Jenny Downs; Elia M Pestana Knight; Heather Olson; Carol-Anne Partridge; Graham Stuart; Marina Trivisano; Sameer Zuberi; Tim A Benke Journal: Front Neurol Date: 2022-06-20 Impact factor: 4.086
Authors: Mary Beth Stosser; Amanda S Lindy; Elizabeth Butler; Kyle Retterer; Caitlin M Piccirillo-Stosser; Gabriele Richard; Dianalee A McKnight Journal: Genet Med Date: 2017-08-24 Impact factor: 8.822