Photo of sleeping newborn baby holding adult thumb to represent newborn genome sequencing to test for treatable genetic disorders.
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Results from a study led by Boston Children’s Hospital show that chromosomal microarray analysis could be a helpful additional test in cases of unexplained sudden infant death syndrome (SIDS).

The study, published in Advanced Genetics, shows that around 12 percent of such cases could be due to copy number or structural genetic mutations. The authors argue that their results support including this kind of genetic test in future SIDS investigations.

“We think we have enough information to say that chromosomal microarray analysis is worth considering when a child has died without explanation, and worth exploring further as a way to understand these deaths better,” says Richard Goldstein, who directs Robert’s Program on Sudden Unexpected Death in Pediatrics at Boston Children’s and was a senior author on the study.

Although copy number variants (CNVs) have been linked to both stillbirth and SIDS in the past, not much is known about the role these variants and the genes near them play in unexplained SIDS.

To investigate further, the researchers carried out chromosomal microarray analysis on samples from 116 deceased infants and toddlers up to the age of 28 months. The cases included in the analysis were either classified as sudden unexplained death in pediatrics (SUDP—including older children) or SIDS (including infants up to 1 year of age). A cohort of autism spectrum disorder children and a control cohort were also tested for comparison purposes.

Pathogenic CNVs were found in five cases, variants of unknown significance that were likely to be pathogenic CNVs in nine cases and structural variants in three cases. Overall, 12.1% of cases in the SIDS/SUDP group could be linked to pathogenic CNVs or structural variants.

Many tests are carried out to try and ascertain why children have died in cases of SIDS and SUDP, including some genetic tests, but not commonly chromosomal microarray analysis.

“Although we did not find any CNVs that definitively explain the cause of death in our SUDP cohort, our findings suggest new avenues to investigate intrinsic vulnerabilities in the SUDP population,” write the authors.

“Notably, the pathogenicity score was significantly increased for deletions in comparison to a control database and was similar to the ASD cohort. In addition, several CNVs are associated with neurodevelopmental phenotypes, including two cases with 47, XXY. These findings raise the question of whether the neurodevelopmental or some other consequence of abnormal gene dosage from these CNVs has contributed to death in these cases.”

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