Abstracts

Rationale: CASE: A full term boy born after an uncomplicated pregnancy and delivery was noted to have episodes of cyanosis and stiffening beginning at 12 hours of age. While on EEG, he was observed to have multiple episodes of forced eye closure, tonic arm flexion with leg extension, apnea and cyanosis with significant desaturation associated with right centroparietal seizures. The EEG background was normal except for multifocal sharp waves. Exam showed mild axial hypotonia and proximal weakness but no other focal neurologic deficits or any dysmorphisms. MRI and MRS were normal. Extensive metabolic testing of the blood, urine and CSF were unremarkable. Chromosomal microarray detected no abnormalities. A NextGeneration epilepsy gene panel, utilizing sequence analysis and exon-level deletion/duplication testing of multiple genes implicated in infantile epilepsy, revealed a disease causing mutation in the KCNQ2 gene (R213W), as well as a missense variant of unknown significance in the SCN1A gene (R542Q). He continued to have 5-12 seizures per day for the first five days despite maximal treatment with phenobarbital or levetiracetam, but seizures stopped with therapeutic fosphenytoin levels. Even with the addition of topiramate and clonazepam, the patient did not tolerate being weaned off of phenytoin and was discharged home at 5 weeks of age on phenytoin and topiramate. At follow-up at 4 months of age, the patient still had mild axial hypotonia but normal development and the decision was made to taper topiramate and continue phenytoin. Methods: . Results: . Conclusions: DISCUSSION: To our knowledge, this is the first report of a child with KCNQ2-associated neonatal seizures also found to have an SCN1A gene mutation. The latter represents a non-conservative amino acid substitution at a highly conserved position that has been previously reported in several individuals with epilepsy, although its causative role has not been established. KCNQ2 mutations have been associated with both benign neonatal seizures, characterized by normal interictal EEG and development with remission of seizures within the first year, and neonatal epileptic encephalopathy, characterized by an initial pattern of burst suppression with significant developmental delay and seizures that last for several years. Our patient's phenotype did not clearly fit either pattern. His interictal EEG was unremarkable and his development has been normal thus far, similar to benign neonatal seizures, but his seizures did not respond to many agents that typically control seizures in these patients and instead were selectively responsive to phenytoin. Animal models have shown interactions between sodium and potassium channel mutations with increased severity of epilepsy (Kearney JA et al, Hum Mol Genet. 2006;15(6):1043-8). Although his phenotype may be entirely due to the KCNQ2 mutation, we suspect a modifying effect of the SCN1A mutation and parental testing is being pursued.