SCN2A A Sequence Variant in Mosaic State in a Patient with Infantile Epileptic Encephalopathy

Introduction: Increasing use of panel analyses (epileptic encephalopathies) leads to identification of sequence variants of unknown significance. The pathogenic relevance may only be assessed in the context of the disease course. A female infant carrying a formerly unknown sequence variant in the SCN2A gene in mosaic state showed clinical response to phenytoin.

Case Report: A girl displayed after uneventful pregnancy and delivery myoclonic and focal seizures starting from the second day of life. EEG showed burst-suppression pattern. Cranial MRI and screening for inborn disorders of metabolism were normal. The seizures persisted despite application of diverse anti-epileptic drugs (phenobarbital, vitamin B6, pyridoxal phosphate, folinate, and levetiracetam). Panel analysis for epileptic encephalopathies was initiated. Upon admittance to our hospital (fifth week) the patient displayed seizures ~10 times per hour. EEGs showed multifocal ETPs, phases of suppression- abortive burst during sleep. Prior to the results of genetic testing, additional AEDs (dexamethasone, zonisamide, vigabatrin) were tested without clinical benefit. With lacosamide, reduction in seizure frequency was achieved. The sequence variant c.2644G > A; p.Gly882Arg in the SCN2A gene was identified in mosaic state in peripheral blood and buccal mucosa. Since it was suggested that neonatal onset of epilepsy correlates with gain-of-function mutations in SCN2A and that sodium channel blockers are often effective, phenytoin treatment was initiated and showed rapid cessation of clinically visible seizures.

Conclusion: (1) A mosaic SCN2A sequence variant in a highly conserved amino acid position can lead to a classical neonatal disease course. (2) Knowledge of the underlying genetic mutation allowed the application of specific AEDs.