A novel pathogenic variant causing POU3F3-related neurodevelopmental disorder in a child presenting with infantile epileptic spasms syndrome: Expanding the epileptic phenotype

Purpose: Pathogenic variants in the POU3F3 gene are responsible for an ultra-rare neurogenetic disorder, characterized by a combination of neuropsychiatric and systemic manifestations. Epilepsy is observed in approximately 15 % of affected individuals, ranging from focal non-motor sensitive seizures (gelastic and dacristic) to generalized motor and non-motor seizures including either tonic-clonic, tonic, myoclonic, atonic or atypical absences. To date, no cases of infantile epileptic spasms have been associated with this neurogenetic condition. Methods: We report on a 20 months male patient presenting at 4 months of life with epileptic spasms, encephalopathic pattern on EEG, confirmed by BASED score, severe hypotonia, microcephaly, cerebral malformation and hyperkinetic movement disorder, consisting of stereotypies and dyskinesias. Epileptic spasms relapsed after ACTH cycle and responded to treatment with vigabatrin. Results: Exome analysis revealed a novel missense de novo pathogenic variant (c.1071G>C; p.Gln337His) in the POU3F3 gene. Conclusions: This case expands the epileptic phenotype of the POU3F3-related neurodevelopment disorder and contributes to the identification of a novel potential gene, involved in the genetic etiology of Infantile Epileptic Spasm Syndrome.