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A Case of Carbamazepine Responsive Neonatal Epilepsy Secondary to PACS2 Gene mutation

Objectives: To describe a unique clinical presentation of the PACS2 gene mutation causing developmental and epileptic encephalopathy (DEE).

Methods: A 2 weeks old Emirati male neonate presented with unprovoked seizures since day 18 of life, after having an uneventful birth and negative family history. The presentation was brief isolated myoclonic jerks in wakefulness. The EEG was normal. On day 30 of life, the infant presented with increased frequency of seizures in wakefulness and sleep. The semiology included high-pitched cry followed by unilateral eye deviation and a staring look with or without asymmetric tonic posturing of the upper limbs with dusky skin discoloration followed by hiccups. Each episode self-aborted in less than 2 minutes, followed by sleep. Levetiracetam at maximal dose failed to control the seizures. EEG showed a normal background with occasional sharp transients. One recorded seizure showed epileptic activity beginning from left and spreading toward right temporal region (Figure 1), reminiscent of migrating focal seizures of infancy or benign neonatal familial epilepsy (BNFE).

Results: The patient was started on Carbamazepine at 10 mg /kg/day in two divided doses. His seizures completely responded within 24 hours. Epilepsy gene panel showed a heterozygous mutation in the PACS2 gene c.625G>A p.(Glu209Lys), which has been reported as de novo in several individuals with DEE. At 3 months age, the patient remains seizure free with normal developmental milestones and normal EEG.

Conclusion: We present a case of PACS2 mutation associated neonatal epilepsy, which clinically and electrographically behaved like BNFE with complete response to Carbamazepine.
Keywords: PACS2 mutation, Developmental and epileptic encephalopathy, neonatal, carbamazepine