Written by Dr. Ramirez and the Research Team at Seattle Children’s Hospital.

Sudden Infant Death Syndrome (SIDS) and Sudden Unexpected Infant Death (SUID) remain devastating tragedies with too many unanswered questions. Our research at Seattle Children’s is dedicated to uncovering the underlying causes of these deaths through genetic and epidemiological studies, with the recent addition of multi-omics approaches. 

Recent findings from their genetic analyses suggest that the same genetic vulnerabilities contributing to SIDS and SUID may also play a role in Sudden Unexplained Death in Childhood (SUDC) or beyond. The prevailing hypothesis suggests that a vulnerable infant may succumb to SIDS/SUID when exposed to an external stressor during a critical developmental period. 

However, it’s possible that in some cases, the infant survives infancy, carrying this vulnerability into childhood or even adulthood. When faced with additional stressors, such as vigorous exercise or illness, they may be overwhelmed and experience death. 

In light of this, we have expanded the focus of our genetic study to include children up to age 17, recognizing the need to better understand sudden unexplained deaths across a broader age range.

Genetic and Multi-Omics Insights
Through the whole genome sequencing of 144 infants, we identified genetic variants in genes linked to cardiomyopathies, arrhythmias, neurologic function, systemic disorders, and immunological function that may cause a susceptibility to these conditions putting the infant at risk of sudden death. Notably, we also discovered new variants in genes involved in the response to hypoxia and the regulation of reactive oxygen species (ROS), marking the first association of these genes with SUID. These findings have provided important clues about the biological mechanisms that may contribute to sudden death. In addition, we have also sequenced the whole genome for an additional 200 infants, for which analysis is underway.

To gain a more comprehensive understanding, we are in the initial stages of integrating transcriptomics, metabolomics, and epigenomics, recognizing that whole genome sequencing alone does not capture the full complexity of these biological mechanisms. By analyzing how gene expression and metabolic activity differ in affected individuals, we aim to build a more comprehensive understanding of risk factors and potential biomarkers for early identification.

Future Directions

Our next steps involve leveraging Machine Learning and AI to uncover critical protein interactions, polygenic inheritance patterns, and gene modifiers that likely contribute to SUID and potentially SUDC—challenges that traditional methods struggle to address due to the vast number of implicated genes. We are actively expanding our collaborations to increase the number of infants and children sequenced. 

One notable collaboration, still in the early phase, involves working with medical examiners in Washington state to integrate whole genome sequencing into autopsies, thereby enhancing the understanding of SUID and SUDC in forensic investigations. 

Our long-term goal is to develop newborn genetic screening to identify infants and children at increased risk, empowering parents and healthcare providers to make informed decisions and adjust care accordingly.

Impact on Families and Professionals

In addition to families affected by SUID/SUDC, our work has significant implications for medical examiners, pediatricians, genetic counselors, grief specialists, and others who support those experiencing these tragedies. By improving risk assessment and advancing scientific understanding, we aim to not only inform prevention efforts but also enhance the support and care provided to families, ensuring that they receive accurate information, appropriate resources, and compassionate guidance during such difficult times.

We are grateful for the collaboration and support of this dedicated community, and we welcome ongoing discussions, data sharing, and participation in research efforts.

Get Involved and Stay Informed

For more information about our ongoing genetic study or to connect with our team, please email us at [email protected] or visit givetostopsids.org. To explore our latest genetic findings, read our publication in the American Journal of Medical Genetics, Part A: https://doi.org/10.1002/ajmg.a.63596.

We also invite you to attend the upcoming 8th annual Microsoft SIDS Summit, a multidisciplinary conference where physicians, research and data scientists, grief support professionals, families, and public health officials come together to share research, foster collaboration, and advance the understanding of SIDS and SUID.

The event will take place March 26th-27th.

To register for this conference, email [email protected] or [email protected].