Copy number variation in fetal alcohol spectrum disorder

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Pediatrics

Background:

• Fetal alcohol spectrum disorder (FASD) encompasses neurological, developmental, and congenital defects resulting from prenatal alcohol exposure.
• Previous research suggests a link between large chromosomal anomalies and FASD.
• Copy number variations (CNVs) represent a significant source of genetic variation with potential implications for developmental disorders.

Purpose of the Study:

• To investigate the prevalence and types of CNVs in a Canadian cohort of children diagnosed with FASD.
• To identify rare CNVs associated with FASD that may contribute to neurodevelopmental impairments.
• To explore the potential role of genetic factors in FASD beyond the effects of alcohol exposure.

Main Methods:

• Genotyping of 95 children with FASD and 87 typically developing controls using the Illumina Human Omni2.5 SNP array.
• Comparison of CNVs in FASD cases with a large population control dataset (10,851 individuals) to identify rare variants (<0.1% frequency).
• Analysis of rare CNVs for impact on potentially clinically relevant developmental genes.

Main Results:

• Rare CNVs were identified in 12 out of 95 (13%) children diagnosed with FASD.
• These rare CNVs affected genes implicated in conditions such as epilepsy and autism (e.g., CACNA1H) and included known chromosomal abnormalities (e.g., 3q29 deletion).
• The findings indicate that chromosomal deletions and duplications may be present in a subset of individuals with FASD, potentially explaining their neurodevelopmental deficits.

Conclusions:

• A significant proportion of children diagnosed with FASD harbor rare CNVs that may contribute to their clinical presentation.
• Genetic investigations, including evaluation by a clinical geneticist, are recommended for children suspected of having FASD, particularly when neurodevelopmental delays are present.
• Identifying underlying genetic etiologies is crucial for accurate diagnosis and management of FASD and related conditions.