Chromosomal microarray testing in adults with intellectual disability presenting with comorbid psychiatric disorders

Area of Science:

• Genetics
• Neuroscience
• Psychiatry

Background:

• Chromosomal copy-number variations (CNVs) are significant genetic contributors to neurodevelopmental disorders like intellectual disability (ID), schizophrenia, and autism spectrum disorders (ASD).
• A substantial proportion of adults with idiopathic ID, particularly those accessing psychiatric services, have not undergone genetic testing for CNVs.

Purpose of the Study:

• To investigate the diagnostic yield of genome-wide chromosomal microarray analysis (CMA) in adults with idiopathic ID presenting to psychiatric services.
• To identify specific CNVs and affected genes associated with idiopathic ID in this population.

Main Methods:

• Genome-wide CMA was performed on 202 adults with idiopathic ID recruited from English psychiatric services.
• CNV pathogenicity was evaluated using standard clinical diagnostic methods.
• Participants received comprehensive medical and psychiatric phenotyping.

Main Results:

• A diagnostic yield of 11% for likely pathogenic CNVs was observed (22 out of 202 individuals).
• Recurrent CNVs in the 15q11-q13 and 16p11.2-p13.11 regions were most common.
• Increased frequency of 16p11.2 duplications and CNVs in neurodevelopmental genes (NRXN1, GRIN2B) were noted.

Conclusions:

• Routine CMA in ID psychiatry services can identify new genetic diagnoses in approximately 11% of adults with idiopathic ID.
• These genetic findings have potential implications for patient management and diagnosis.
• Increased consideration of CMA is recommended for the assessment of adults with idiopathic ID in psychiatric settings.