Related Experiment Video
Updated: Aug 5, 2026
The Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders
Published on: August 5, 2017
Increased Prevalence of Rare Copy Number Variants in Australian Children With Fetal Alcohol Spectrum Disorder:
Suzy Byrnes1,2, Felicity Collins1,3, Elizabeth Elliott1,2
1Faculty of Medicine and Health, Specialty of Child and Adolescent Health, The University of Sydney, Sydney, New South Wales, Australia.
Insights
Approximately 24% of children with fetal alcohol spectrum disorder (FASD) have rare DNA copy number variants (CNVs). Genetic testing can aid FASD diagnosis and identify genetic vulnerabilities.
Area of Science:
- Genetics
- Neurodevelopmental Disorders
- Pediatrics
Background:
- Prenatal alcohol exposure (PAE) can lead to fetal alcohol spectrum disorder (FASD), a condition with neurodevelopmental impairments.
- Genetic factors are suspected to influence FASD phenotypes.
- Identifying genetic variants in children with FASD is crucial for understanding disease mechanisms.
Purpose of the Study:
- To determine the prevalence and types of DNA copy number variants (CNVs) in children diagnosed with FASD.
- To identify genes associated with neurodevelopmental disorders within the FASD cohort.
Main Methods:
- Chromosomal microarray (CMA) was performed on 175 children diagnosed with FASD.
- A retrospective chart review was conducted for medical history, phenotype, and genotype data.
- CMA results were analyzed by a clinical geneticist.
Main Results:
- A rare CNV was found in 24.2% of children tested.
- Four patients had identified neurodevelopmental susceptibility syndromes.
- 84.2% of CNVs identified were variants of unknown significance (VOUS), with 13 encoding genes linked to neurodevelopmental disorders.
Conclusions:
- About one in four children with FASD may have a rare CNV, with most currently of uncertain clinical significance.
- Genetic testing can support FASD diagnosis.
- Genetic testing may reveal additional diagnoses or genetic vulnerabilities to FASD.
Background:
Prenatal alcohol exposure (PAE) can result in fetal alcohol spectrum disorder (FASD), a permanent, heterogeneous condition characterized by severe neurodevelopmental impairments with or without microcephaly, characteristic facial dysmorphology, and congenital anomalies. Clinical and pre-clinical studies suggest that genetic factors, in the mother or fetus, influence the phenotypic outcomes following PAE. The objectives of this study were to evaluate the prevalence and types of DNA copy number variants (CNVs) in children (0-18 years) diagnosed with FASD and to identify genes known to be associated with neurodevelopmental disorders.
Methods:
Chromosomal microarray (CMA) was performed in children diagnosed with FASD in the NSW CICADA FASD Service-a state-wide multidisciplinary diagnostic clinic in Australia. We performed a retrospective chart review of 175 patients diagnosed with FASD between 2015 and 2022 to obtain data on medical and family history, phenotype, and genotype. All CMA results were reviewed by a clinical geneticist.
Results:
A rare CNV was identified in 38 of 157 (24.2%) patients who had CMA testing and 40 unique CNVs were identified. In four patients, a neurodevelopmental susceptibility syndrome was identified including Xq28 microduplication syndrome, 16p12.2 microdeletion syndrome, 17q11.2 microduplication syndrome, and an atypical variant of 22q11.2 deletion syndrome. Two children had incidental pathogenic variants. In 32 of 38 (84.2%) cases with a rare CNV, 34 variants of unknown significance (VOUS) were identified, of which 13 encoded a total of 14 genes associated with common neurodevelopmental disorders. Three variants of uncertain significance (VOUS) encoded different subunits of the voltage-dependent calcium channel complex protein (CACNB2, CACNA1A, CACNA2D3).
Conclusion:
These novel results suggest that approximately one in four children diagnosed with FASD may harbor a rare CNV, of which 85.0% are currently of uncertain clinical significance. Genetic testing can support the FASD diagnostic process and may reveal additional diagnoses or sources of genetic vulnerability to FASD.
Related Concept Videos
02:26Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
02:30Genomic Imprinting and Inheritance
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
01:19Autism Spectrum Disorder
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.