title: The variable phenotypes of KCNQ-related epilepsy.
abstract: Mutations in KCNQ2 and KCNQ3 were originally described in infants with benign familial neonatal seizures (BFNS). Recently, KCNQ2 mutations have also been shown to cause epileptic encephalopathy. This report describes three infants carrying abnormalities of KCNQ2 and one infant with a KCNQ3 mutation. The different KCNQ2 abnormalities led to different phenotypes and included a novel intragenic duplication, c.419_430dup, in an infant with BFNS, a 0.761Mb 20q13.3 contiguous gene deletion in an infant with seizures at 3 months, and a recurrent de novo missense mutation c.881C>T in a neonate with "KCNQ2-encephalopathy." The mutation in KCNQ3, c.989G>A, was novel and occurred in an infant with BFNS. KCNQ-related seizures often present with tonic/clonic manifestations, cyanosis, or apnea. Certain genotype-phenotype correlations help predict outcome. Similarly affected family members suggests benign familial "KCNQ-related" epilepsy, whereas neonatal seizures with unexplained multifocal epileptiform discharges or burst suppression on electroencephalography, and acute abnormalities of the basal ganglia/thalami are suggestive of KCNQ2-encephalopathy, which is often sporadic. 20q13.33 contiguous gene deletion encompassing KCNQ2 may harbor atypical features depending on deletion size. Although the phenotype often guides direct targeted gene testing in these conditions, array CGH should also be considered in suspected sporadic or atypical familial cases to diagnose 20q13.33 deletion.
authors: Department of Paediatric Neurology & Clinical Neurophysiology, Children's University Hospital, Dublin, Ireland.
authors: Nicholas M
authors: NM
authors: Allen
authors: Maria
authors: M
authors: Mannion
authors: Judith
authors: J
authors: Conroy
authors: Sally A
authors: SA
authors: Lynch
authors: Amre
authors: A
authors: Shahwan
authors: Bryan
authors: B
authors: Lynch
authors: Mary D
authors: MD
authors: King
mesh_terms: D001479:Basal Ganglia / Q000473:pathology; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051656:KCNQ Potassium Channels / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D013788:Thalamus / Q000473:pathology
chemical_list: D051656:KCNQ Potassium Channels
keywords: Array CGH; CHRNA4; Encephalopathy; Epilepsy; KCNQ2; KCNQ3