A novel KCNQ2 gene mutation in a patient with self-limitted non-familial neonatal epilepsy: a case report

Background: In several genetic epilepsies, the genotype-phenotype relationship is complex in which pathogenic variants in the same gene may causes different epilepsy phenotypes. As a typical example, pathogenic variants of KCNQ2 have been known to cause either self-limited familial (and non-familial) neonatal epilepsy or early-onset epileptic encephalopathies. In spite of very different prognosis in terms of both epilepsy and development, both usually present as neonatal seizures within the first week of life. Case presentation: The patient, who was born at term after an uneventful pregnancy, had onset of tonic seizures at 2 days of age. Family history was negative for seizures or epilepsies. During the early stage (from onset to 6 months of age), he exhibited some electroclinical features resembling epileptic encephalopathy, including marked abnormalities on electroencephalogram, poor response to epileptic medications, hypotonia, and mild motor developmental delay. However, his seizures remitted from 4 months of age. And at his last evaluation at 20 months old, he presented cognitive and motor development within the normal range. His outcome, therefore, is more consistent with self-limited neonatal epilepsy. Whole exome sequencing followed by Sanger sequencing confirmation revealed that the patient had a heterozygous mutation c.1030T>G (p.Trp344Gly) in KCNQ2 gene which has not been previously reported. Examination of this mutation in the parents implied that this mutation occurred de novo. This mutation was classified as ``likely pathogenic'' according to standards of The American College of Medical Genetics and Genomics. Conclusions: This study reported a rare case of self-limited non-familial neonatal epilepsy with a novel KCNQ2 gene mutation. It should be cautious that some patients with KCNQ2-self-limited non-familial neonatal epilepsy may present some features resembling epileptic encephalopathy at onset/early stage. The complex genotype–phenotype correlation of KCNQ2-related epilepsies and the genetic counselling involved with the case are also discussed in this case report.