Autism spectrum disorder and comorbid neurodevelopmental disorders (ASD-NDDs): Clinical and genetic profile of a pediatric cohort

Clin Chim Acta. 2022 Jan 1:524:179-186. doi: 10.1016/j.cca.2021.11.014. Epub 2021 Nov 17.


Background: Autism spectrum disorder (ASD), a neurodevelopmental disorder, is featured by impaired social communication and restricted and repetitive behaviors and interests. ASD and comorbid neurodevelopmental disorders (ASD-NDDs), especially epilepsy and intellectual disability (ID)/global developmental delay (GDD) are frequently presented in genetic disorders. The aim of this study was to explore the clinical and genetic profile of ASD in combination with epilepsy or ID/GDD.

Methods: We retrospectively analyzed the clinical characteristics, and genetic spectrum of pediatric patients presenting ASD-NDDs with proven genetic etiology. The pathogenicity of variants was conducted by molecular geneticists and clinicians complied with the guidelines of the American College of Medical Genetics and Genomics (ACMG).

Results: Among 154 patients with ASD-NDDs, 79 (51.3%) patients gained a genetic diagnosis. Most patients (78/79, 98.7%) had comorbid ID or GDD, and 49 (49/79, 62.0%) had comorbid epilepsy. The clinical characteristics of those 79 patients were varied. 87 genetic variants were found among the 79 pedigrees. Most of the involved genes have roles in gene expression regulation (GER) and neuronal communication (NC). Most genes have been proven to be ASD-related genes, and some of them were not reported to contribute to ASD previously.

Conclusion: We summarized the genetic and clinical profile of 79 ASD-NDDs patients with proven genetic etiology. The genetic spectrum of ASD was expanded, and we highlighted a novel possible ASD candidate gene PRTG.

Keywords: Autism spectrum disorder; Comorbidity; Epilepsy; Gene; Intellectual disability.

MeSH terms

  • Autism Spectrum Disorder* / diagnosis
  • Autism Spectrum Disorder* / epidemiology
  • Autism Spectrum Disorder* / genetics
  • Child
  • Genetic Profile
  • Humans
  • Intellectual Disability* / diagnosis
  • Intellectual Disability* / epidemiology
  • Intellectual Disability* / genetics
  • Neurodevelopmental Disorders* / epidemiology
  • Neurodevelopmental Disorders* / genetics
  • Retrospective Studies