Collaborative Research Partnership

Boston Children's Hospital
Harvard Medical School

Are X-linked genes linked to reduced substance P NK1 receptor expression in sudden and unexplained death in infants?

Robert Vink, Roger W. Byard and Leanne Dibbens
University of South Australia and The University of Adelaide


More boys die from sudden and unexplained death in infancy (SIDS or SUDI) than girls. This suggests that there may be a genetic reason placing boys at greater risk than girls, presumably with the responsible genes being linked to the female X chromosome (1). However, to date, no gene candidate has been identified.

With previous funding from River’s Gift, it was discovered that a receptor linked to a chemical neurotransmitter in the brain, substance P, which controls respiration and head/neck movement, is reduced in babies who have died suddenly and unexpectedly (1). The reduction in this receptor may account for the inability of vulnerable infants to breathe when subject to hypoxic conditions (eg., face down) as well as the inability to simply lift their faces to escape the dangerous environment (2). Notably, genes located on the X chromosome control the synthesis of this receptor. This study will use DNA extracted from blood samples collected at postmortem examination to characterise whether there is any link between these X-linked genes and sudden and unexpected death in babies.

Significance and Proposed Outcomes of the current project

This study will identify mutations of the X-linked micro RNA 500 and 320 genes that regulate substance P, NK1 receptor expression in the brainstem, and will characterize the relationship between any such mutations and the diagnosis of SUDI. Given that this is the first identified association between the X chromosome and respiratory control, we have before us the exciting possibility that mutations in these two genes may account for a significant proportion of SUDI cases seen in the worldwide population. Furthermore, this discovery may lead to a relatively cheap diagnostic test becoming available to identify infants at risk for SUDI, thus resulting in better management of vulnerable infants during the first year of life. The second significant outcome is that the DNA extracted from the blood spots will also be used to create the first SIDS DNA biobank in the world. Using protected technology developed in the creation of the world’s first epilepsy biobank, DNA samples of high purity can be extracted and stored for in excess of 20 years and still be successfully used for experimental studies. This biobank will thus become a resource for future molecular genetics studies, even for genes that are yet to be discovered.


Bright FM, Vink R, Byard RW, Duncan JR, Krous H, Paterson DS. Abnormalities in substance P neurokinin-1 receptor binding in key brainstem nuclei in sudden infant death syndrome related to prematurity and sex. PLoS One 2017;12:e0184958.
Byard RW, Bright F, Vink R. Why is a prone sleeping position dangerous for certain infants? Forensic Sci Med Pathol 2018;14:114-6.

La Trobe University

Between April-September 2018, River’s Gift partnered with Latrobe University, Safe Sleep Space and Soteria Safe Sleeping Advice in conducting an ethics approved Safe Sleep and Settling Knowledge survey.

The survey was conducted amongst more than 2,000 Australian participants and, disturbingly, it was found that there were substantial shortfalls in safe sleep and settling knowledge amongst portions of the participant cohort. The research paper is currently in development, with anticipation for it to be published in late 2019.

Global research evidence clearly represents that safe sleep practices heavily reduces the risk of an Apparent Life Threatening Event (ALTE) in sleep, helping to protect the lives of infants in their first year of life. Safe sleep practices play a major part in eliminating fatal sleep accidents and SIDS cases in infants, as current day research clearly shows that reducing potential stressors on infants is a critical piece of solving the SIDS puzzle.

Leveraging off the research project, a pilot safe sleep education program is being undertaken with the clear-cut objective of optimising safe sleep knowledge of Geelong parents, grandparents, health professionals and caregivers; helping to ensure the safety and survival of infants in our region. Beyond completion of the pilot program in late 2019, River’s Gift aim to continue delivering vital education services in 2020 onwards to key markets in Geelong, with an aim of extending the program nationwide in the future.