Duplication within the KCNQ2 Gene in a Child with Benign Early-Onset Epileptic Encephalopathy

Abstract

Introduction: Mutations in the KCNQ2 gene lead to autosomal dominant benign neonatal seizures or early-onset epileptic encephalopathy. We describe here a female patient with focal epileptic seizures starting from four months of age, carrying a heterozygous duplication of exons 9 – 17 of the KCNQ2 gene. Case Presentation: It is the second child of German non-consanguineous parents without any family history for seizures or epilepsy. After uneventful pregnancy, delivery and neonatal period, the patient developed focal seizures with impairment of awareness several times per week. Cranial MRI, screening for inborn disorders of metabolism or prenatal infections (TORCH) did not show pathogenic results. A panel analysis for epileptic encephalopathies (CeGaT) revealed a heterozygous duplication of exons 9 to 17 of the KCNQ2 gene which was classified as variant of unknown significance. With application of Levetiraetam (at least 40 mg/kg daily, blood level of ~10 μg/mL) absence of seizures except for febrile situations was achieved. After the 7th month, no more seizures were observed, even during infections, and Levetiraetam therapy could be gradually reduced and finally stopped. Psychomotor development of the patient is almost normal. Due to muscular hypotonia, she received physiotherapy, but the developmental milestones were all reached age-appropriately. Conclusion: The clinical interpretation of variants of unknown significance revealed through a panel analysis is often difficult, even with incorporation of data from large databases. So far, a partial KCNQ2 duplication, of exons 3 to 12, has been described only once in the literature in a patient with benign neonatal epilepsy. The reported disease course in our patient carrying another partial duplication of KCNQ2 suggests a benign outcome in this family as well.