KCNQ2 mutations were identified in 10% (8/80) of patients with unexplained neonatal or early-infantile seizures, presenting with a distinct electroclinical and radiological phenotype.
Observational (n=80)
Are KCNQ2/3 mutations a frequent cause of early-onset epileptic encephalopathies with a recognizable phenotype?
KCNQ2 mutations account for 10% of unexplained neonatal epileptic encephalopathies, presenting with a distinct electroclinical and radiological phenotype.
OBJECTIVE: KCNQ2 and KCNQ3 mutations are known to be responsible for benign familial neonatal seizures (BFNS). A few reports on patients with a KCNQ2 mutation with a more severe outcome exist, but a definite relationship has not been established. In this study we investigated whether KCNQ2/3 mutations are a frequent cause of epileptic encephalopathies with an early onset and whether a recognizable phenotype exists. METHODS: We analyzed 80 patients with unexplained neonatal or early-infantile seizures and associated psychomotor retardation for KCNQ2 and KCNQ3 mutations. Clinical and imaging data were reviewed in detail. RESULTS: We found 7 different heterozygous KCNQ2 mutations in 8 patients (8/80; 10%); 6 mutations arose de novo. One parent with a milder phenotype was mosaic for the mutation. No KCNQ3 mutations were found. The 8 patients had onset of intractable seizures in the first week of life with a prominent tonic component. Seizures generally resolved by age 3 years but the children had profound, or less frequently severe, intellectual disability with motor impairment. Electroencephalography (EEG) at onset showed a burst-suppression pattern or multifocal epileptiform activity. Early magnetic resonance imaging (MRI) of the brain showed characteristic hyperintensities in the basal ganglia and thalamus that later resolved. INTERPRETATION: KCNQ2 mutations are found in a substantial proportion of patients with a neonatal epileptic encephalopathy with a potentially recognizable electroclinical and radiological phenotype. This suggests that KCNQ2 screening should be included in the diagnostic workup of refractory neonatal seizures of unknown origin.
Weckhuysen et al. (2011) conducted an observational in Unexplained neonatal or early-infantile seizures and associated psychomotor retardation (n=80). KCNQ2 and KCNQ3 mutation screening was evaluated on Presence of KCNQ2 mutations. KCNQ2 mutations were identified in 10% (8/80) of patients with unexplained neonatal or early-infantile seizures, presenting with a distinct electroclinical and radiological phenotype.
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