First Tunisian case of FGF12-related neonatal epileptic encephalopathy

Abstract

Despite advancements in neonatal care, treatment of neonatal-onset epilepsy is complex and highly challenging. Here, we report the case of a Tunisian newborn whose seizures began at two days of life and whose genetic testing identified a recurrent de novo gain-of-function missense mutation in FGF12 gene (p.R114H in long isoform transcript, p.R52H in the short isoform transcript). The patient showed resistance to multiple antiepileptic treatments but noteworthy lamotrigine, escalated from 2.5 to 25 mg/day, resulted in an initial decrease in seizure frequency. Later the combination of phenobarbital (5 mg/kg) and valproic acid (VPA) (20 mg/kg) reduced the frequency of seizures substantially. At two years of age, the patient showed hypotonia with severe global developmental delay, occasional seizures, and required tube feeding. Our findings underscore the phenotypic variability and therapeutic challenges associated with FGF12-related epilepsy. Early seizure control is imperative for optimizing neurological outcomes in affected individuals, without mentioning the need for advanced research into gene-based treatment strategies.