Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina

Abstract

Purpose

Infantile Epileptic Spasms Syndrome (IESS) is the most prevalent epileptic encephalopathy (EE) in the first year of life, with approximately 40 % of cases of genetic or unknown origin. This study aims to describe the clinical and molecular characteristics of a group of Argentine patients diagnosed with IESS of unknown etiology.

Methods

A retrospective analysis was performed on the clinical data of 24 pediatric patients diagnosed with IESS with hypsarrhythmia, who underwent genomic studies between 2019 and 2022.

Results

A genetic etiology was identified in 50 % of cases (eight boys and four girls; median seizure onset age: 3 months). Most of them initiated with IESS and over half evolved into Lennox-Gastaut syndrome. Developmental delay preceded seizure onset in all patients, persisting or worsening thereafter. Notable features included hypotonia, microcephaly, and dysmorphisms. Half of the patients had a family history of epilepsy, and two of EE. Identified variants included 7/13 (53.8 %) single nucleotide variants in KCNQ2, STXBP1, SCN8A, CDKL5, UGDH, and WWOX; 5/13 (38.5 %) copy number variants involving the genes UBE3A-GABRB3-GABRA5, SCN2A-SCN1A-SCN9A, and WWOX; and a short tandem repeat in ARX. Inheritance patterns included autosomal dominant (n = 8), recessive (n = 2), and X-linked (n = 2). Nine variants (69.2 %) were presumed de novo.

Conclusion

These findings underscore the extensive genetic heterogeneity of IESS within the Argentine population, enriching the international literature and variant databases with Latin American data. In cases with an unknown cause, genetic testing is crucial in establishing an etiological diagnosis, guiding appropriate treatment, and facilitating genetic counseling.