KCNQ2 Epileptic Encephalopathy in Early Infancy

Excerpt

To the Editor: A 12-mo-old boy was first seen at 50 d of life for repeated focal tonic seizures and excessive lethargy. He was term born, second in birth order to a non-consanguineous couple with an uneventful perinatal period. At 18 h of life, he had repeated episodes of focal tonic seizures and excessive irritability with a clinical response to phenobarbitone therapy. At 50 d of life, the child was readmitted with multiple polymorphic seizures (focal tonic seizures, versive eye movements, and occasional multifocal clonic jerks). By 8 mo, the child had developed frequent therapy-resistant seizures with no gain of developmental milestones. A trial of Phenytoin, Valproate, Topiramate, Vigabatrin and Levetiracetam were ineffective. Family history was not contributory. Physical examination revealed no facial dysmorphism, a small head (OFC between −2 to −3 Z score), hypertonia, hyperreflexia, and visual inattention. EEG showed a severely abnormal background with multifocal interictal epileptiform discharges (IEDs). MRI brain was unremarkable. CSF Pipecolic acid and CSF Glycine were within normal range. Next generation sequencing for Early Infantile Epileptic Encephalopathy genes (60 Genes) revealed a heterozygous missense variation in exon 6 of KCNQ2 gene (chr20:62,070,967; A > A/G; c.911 T > T/C). The mutation was later validated by Sanger sequencing. Parental studies were unremarkable suggesting a possible de-novo mutation. The child responded to oral Carbamazepine and Benzodiazepines with complete seizure control. On follow-up at 24 mo, the child had a profound developmental failure with poor visual attention, microcephaly, spastic quadriparesis and was seizure free for 10 mo after starting Carbamazepine. …