Objective:

Not applicable

Background:

The chromodomain helicase DNA-binding protein 2 (CHD2) gene regulates gene activity by remodeling chromatin and plays an essential role in brain developement. CHD2-related early-onset epileptic encephalopathy is characterized by refractory seizures, including myoclonic-atonic seizures and cognitive slowing; regression may occur. Variable seizure semiologies have been described and EEG may show generalized spike-wave discharges. Comorbid autism spectrum disorder (ASD) and intellectual disability is common. De novo pathogenic variants account for the majority of cases reported in the literature. Notably, as few affected individuals are described in the literature, a full description of the condition is not known.

Design/Methods:

not applicable

Results:

We report the clinical case of a 33-year-old male with mild intellectual delay, ASD, and focal epilepsy who underwent genetic testing (Invitae) and was diagnosed with a CHD2-related neurodevelopmental disorder. The patient was born full-term via vaginal delivery and was diagnosed with ASD in childhood after experiencing delayed milestones. He completed his high school degree with special education classes. At age 18, he experienced his first seizure. Semiology was that of staring with stiffening then generalized tonic-clonic activities with bladder incontinence. Seizures were controlled with oxcarbazepine monotherapy. MRI brain was unremarkable and electroencephalograms (EEGs) revealed interictal multifocal epileptiform discharges. Genetic testing identified a novel pathogenic variant in the CHD2 gene with a deletion at exons 21-39.

Conclusions:

This specific CHD2 pathogenic variant has not been previously reported in the literature. It disrupts a region of the CHD2 protein where other pathogenic variants, such as p.Trp1261Leu, have been identified. Our patient exhibited a milder phenotype compared to that of previously reported phenotypes associated with CHD2-related neurodevelopmental disorders in the literature. Our patient had well-controlled focal epilepsy and only mild intellectual disability. Genetic testing should be considered in patients presenting with focal epilepsy and ASD and/or intellectual disability.