Genetic testing in children and adolescents with intellectual disability

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Psychiatric Genetics

Background:

• Intellectual disability (ID) has complex genetic underpinnings.
• High comorbidity exists between ID and psychiatric disorders.
• Advances in genetic technologies are revolutionizing etiological investigations.

Purpose of the Study:

• To review the assessment of copy number variants (CNVs) and single nucleotide variations in ID.
• To discuss the diagnostic yields of various next-generation sequencing (NGS) assays.
• To explore the relationship between ID-pathogenic variants and psychiatric disorder risk.

Main Methods:

• Review of current literature on genetic variant assessment in ID.
• Analysis of diagnostic yields from genome-wide CNV and whole exome sequencing (WES).
• Examination of genotype-phenotype correlations for ID and psychiatric conditions.

Main Results:

• Whole exome sequencing offers higher diagnostic yields (approx. 40%) compared to genome-wide CNV analysis (approx. 15%).
• Specific CNVs linked to ID are significant risk factors for neurodevelopmental disorders like autism, ADHD, and schizophrenia.
• NGS assays can identify etiological variants in most children with ID.

Conclusions:

• NGS-based assays are powerful tools for diagnosing genetic causes of ID.
• Variants causing ID are strongly associated with increased risk for child and adolescent psychiatric disorders.
• Challenges persist in variant pathogenicity assessment, incidental findings, and prognostic determination, especially concerning psychiatric comorbidities.