Abstract
Background: Pathogenic variants in the NEXMIF gene have been linked to a broad neurodevelopmental phenotype, encompassing autism spectrum disorder, intellectual disability, and epilepsy. Among epileptic manifestations, Jeavons Syndrome was observed in 24% of affected females in the largest cohort of NEXMIF-related disorders reported to date, but long-term adult outcomes remain poorly documented. Methods and Results: We report a 25-year-old Italian woman with drug-resistant Jeavons syndrome in which the combined approach of next-generation sequencing and chromosomal microarray analysis allowed us to identify, after a 13-year diagnostic odyssey, a de novo ~350 Kb microdeletion at Xq13.2q13.3 encompassing the entire NEXMIF coding region, with no other OMIM genes involved. To our knowledge, this is the first reported case of a patient harboring a deletion restricted to the entire coding sequence of the NEXMIF gene. The patient presented with moderate intellectual disability and seizure onset at age 10 years. Her epilepsy proved refractory to multiple antiseizure medications. Video-EEG/polygraphic monitoring at age 23 years confirmed epilepsy with eyelid myoclonia, demonstrating characteristic eyelid myoclonia with absences triggered by eye closure. Conclutions: This case provides a detailed clinical description of an adult patient useful for genetic counseling regarding adult outcomes and prognostic expectations. Furthermore, this study underscores the diagnostic value of chromosomal microarray analysis alongside next-generation sequencing in individuals with intellectual disability and drug-resistant epilepsy, in order to expedite the diagnostic pathway and enable timelier and more appropriate patient management.