Array-Based Comparative Genomic Hybridization Analysis in Children with Developmental Delay/Intellectual Disability

Area of Science:

• Genetics
• Developmental Biology
• Medical Diagnostics

Background:

• Developmental delay (DD) and intellectual disability (ID) are conditions affecting early childhood development, characterized by delayed milestones and impaired cognitive functions.
• These conditions exhibit significant genetic heterogeneity, complicating diagnosis through conventional methods.
• Array-based comparative genomic hybridization (aCGH) offers higher resolution for detecting genomic copy number variations (CNVs) compared to traditional cytogenetic techniques.

Purpose of the Study:

• To evaluate the clinical utility of aCGH in diagnosing isolated and syndromic DD/ID cases.
• To correlate identified genetic variations (CNVs) with observed clinical phenotypes.
• To determine the diagnostic yield of aCGH as a first-tier test for DD/ID.

Main Methods:

• Analysis of 139 pediatric cases (77 female, 62 male) diagnosed with DD/ID.
• Application of aCGH to detect CNVs across the genome.
• Clinical data collection for genotype-phenotype correlation.

Main Results:

• aCGH identified 38 distinct CNVs in 35 cases.
• Pathogenic CNVs were found in 13.6% of cases, and likely pathogenic CNVs in 3.5%, yielding an overall diagnostic rate of 17.1%.
• The study detected rare microdeletion/microduplication syndromes, contributing to genotype-phenotype correlation data.

Conclusions:

• aCGH is a highly effective first-tier diagnostic tool for DD/ID, significantly increasing diagnostic yields.
• The identification of specific CNVs aids in understanding the genetic basis of DD/ID and refining genotype-phenotype correlations.
• This approach facilitates the diagnosis of rare genetic syndromes, improving patient management and genetic counseling.