The variable phenotypes of KCNQ ‐related epilepsy

Summary Mutations in KCNQ 2 and KCNQ 3 were originally described in infants with benign familial neonatal seizures ( BFNS ). Recently, KCNQ 2 mutations have also been shown to cause epileptic encephalopathy. This report describes three infants carrying abnormalities of KCNQ 2 and one infant with a KCNQ 3 mutation. The different KCNQ 2 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 “ KCNQ 2‐encephalopathy.” The mutation in KCNQ 3, 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 KCNQ 2‐encephalopathy, which is often sporadic. 20q13.33 contiguous gene deletion encompassing KCNQ 2 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.