Concurrent Developmental Regression and Neurocognitive Decline in a Child With De Novo CHD8 Gene Mutation

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder. Unique ASD subtypes have been proposed based on specific genotype-phenotype combinations. The ASD subtype associated with various chromodomain helicase DNA-binding protein 8 (CHD8) mutations has been associated with an incidence of autistic regression greater than that of all-cause ASD, but the mean age of onset of this subtype remains unknown.

Here we describe a patient with a known de novo CHD8 gene mutation (heterozygous c.2565del) who experienced a profound developmental regression and neurocognitive decline at age 13 years following periods of acute viral illness.

The patient developed treatment-refractory catatonia and self-injurious behaviors leading to marked facial disfigurement. Unfortunately, interventions with immunomodulatory medications, psychotropic medications, and electroconvulsive therapy did not lead to sustained symptom improvement or a full return to baseline.

Our case demonstrates a clinical scenario in which a devastating developmental regression and neurocognitive decline occurred with profound accentuation of previously identified autistic features at an age atypical for autistic regression, following sequential viral infections, thereby raising the question of whether immune dysregulation may be a contributing factor. Regression in patients with monogenic mutations in the CHD8 gene warrants further study to elucidate the mechanisms of illness and the anticipated developmental trajectory.