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A novel pathogenic variant causing POU3F3-related neurodevelopmental disorder in a child presenting with infantile
Gaetano Terrone1, Emilia Cirillo2, Francesca Ripoli2
1Child Neurology and Psychiatry, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
Insights
A novel POU3F3 gene variant caused infantile epileptic spasms, expanding the known POU3F3-related neurodevelopmental disorder phenotype. This finding may link POU3F3 to Infantile Epileptic Spasm Syndrome.
Area of Science:
- Neurogenetics
- Epileptology
Background:
- POU3F3 gene variants cause a rare neurogenetic disorder with neuropsychiatric and systemic issues.
- Epilepsy affects 15% of individuals with POU3F3-related disorders, but infantile epileptic spasms were previously unassociated.
Purpose of the Study:
- To describe a case of infantile epileptic spasms associated with a POU3F3 gene variant.
- To expand the understanding of the POU3F3-related neurodevelopmental disorder phenotype.
Main Methods:
- Case report of a 20-month-old male with infantile epileptic spasms, hypotonia, microcephaly, and movement disorders.
- EEG analysis revealed an encephalopathic pattern (BASED score positive).
- Whole exome sequencing identified a de novo pathogenic variant in the POU3F3 gene.
Main Results:
- A novel missense de novo pathogenic variant (c.1071G>C; p.Gln337His) was found in the POU3F3 gene.
- The patient presented with epileptic spasms, severe hypotonia, microcephaly, cerebral malformation, and hyperkinetic movement disorder.
- Epileptic spasms responded to vigabatrin after relapsing post-ACTH treatment.
Conclusions:
- This case expands the epileptic phenotype associated with POU3F3 gene variants.
- The findings suggest POU3F3 may play a role in the genetic etiology of Infantile Epileptic Spasm Syndrome.
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.
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