London: Rare genetic
mutations associated with impairment of the breathing muscles are more
common in children who have died from sudden infant death syndrome,
according to a new study led by UCL researchers. The study, published in The Lancet, suggests a possible genetic element of the disorder, which is also known as ‘cot death’. “Our study is the first to link a genetic cause of weaker
breathing muscles with sudden infant death syndrome, and suggests that
genes controlling breathing muscle function could be important in this
condition. However, more research will be needed to confirm and fully
understand this link,” said the study’s senior author Professor Michael
Hanna (UCL Institute of Neurology).
These mutations are very rare, and typically found in fewer
than five people in every 100,000. However, the study found mutations
of this kind in four of the 278 children who had died of sudden infant
death syndrome, compared to none of the 729 healthy controls.
“We think the genetic mutations we found may have
contributed to why some of these infants died but are likely to have
interacted with other risk factors and would not necessarily be the sole
cause of death,” said the study’s last author, Dr Emma Matthews (UCL
Institute of Neurology).
Sudden infant death syndrome is the unexpected death of a
seemingly healthy child. It is the leading cause of post-neonatal death
in high income countries, but deaths are rare, and an individual baby’s
risk is low. Typically, it affects children aged between 2-4 months, and
accounts for 300 deaths each year in the UK.
The cause of the disorder is unknown, but babies being
unable to regulate their breathing is thought to be an important
component. Putting babies to sleep on their back, and not sleeping in
the same bed as a parent is known to reduce the risk.*
The study looked at the prevalence of mutations in the
SCN4A gene which codes for an important cell surface receptor (a
skeletal muscle sodium ion channel protein). The expression of this cell
receptor in breathing muscles is low at birth and increases over the
first two years of life.
Mutations in this gene are associated with a range of
genetic neuromuscular disorders and with life-threatening pauses in
breathing, and spasms of the vocal cords that make breathing or speaking
temporarily difficult.
The study included two cohorts of children who had died
from sudden infant death syndrome in the UK and USA, including 278
children overall (84 from the UK and 194 from the USA). All deaths were
unexplained after thorough post-mortem investigations. These were
matched with 729 adults who had no history of cardiovascular,
respiratory or neurological disease.
Their genes were analysed to identify whether they had a
mutation in the SCN4A gene, and to confirm whether the mutations
affected the cell surface receptor that the gene codes for.
While the study found general mutations in the SCN4A gene
in six of the 284 infants who died, and in nine of the 729 controls,
mutations that disrupted the cell surface receptor were only found in
four of the children who had died of sudden infant death syndrome, and
none of the controls.
As the disruptive variants are over-represented in this
group, the researchers say this could indicate a genetic element of
sudden infant death syndrome.
The mutation could cause the cell receptor to become more
commonly used, leaving these children with weaker breathing muscles,
and, if an external stressor impacts their breathing (such as tobacco
smoke, getting tangled in bedding, a minor illness or a breathing
obstruction), they may be less able to catch their breath.
As SCN4A variants are found in some adults with neuromuscular disease, the mutations are not always lethal.
“While there are drug treatments for children and adults
with genetic neuromuscular disorders caused by SCN4A gene mutations, it
is unclear whether these treatments would reduce the risk of sudden
infant death syndrome, and further research is essential before these
findings can become relevant to treatment,” said Professor Hanna.
“We are very pleased that leading researchers continue to
try and identify the cause of SIDS, which leads to the death of around
four babies every week in the UK. In the meantime, we urge all parents
to continue to follow our safer sleep advice to reduce the risk of SIDS:
always place your baby on their back, in their own cot or Moses basket,
in the same room as you for all sleeps, day and night,” said Francine
Bates, CEO of The Lullaby Trust, in a supporting statement.
This study was funded by the Medical Research Council,
Wellcome, National Institute for Health Research, British Heart
Foundation, Biotronik, Cardiac Risk in the Young, Higher Education
Funding Council for England, Dravet Syndrome UK, Epilepsy Society,
National Institutes of Health, and the Mayo Clinic. It was conducted by
researchers from UCL, the National Hospital for Neurology and
Neurosurgery, St George’s University of London and St George’s
University Hospitals NHS Foundation Trust, Mayo Clinic, Chalfont Centre
for Epilepsy, University of Edinburgh, Western General Hospital, Royal
Infirmary of Edinburgh, The Heart Centre, Copenhagen University
Hospital, Rigshospitalet, University of Copenhagen, Sheffield Children’s
NHS Foundation Trust, University of Bristol and King’s College London.
Links
- *Note: For more information on safe sleeping practices for babies, see the NHS guidelines
- Research paper in The Lancet
- Professor Michael Hanna's academic profile
- Dr Emma Matthews' academic profile
- MRC Centre for Neuromuscular Diseases, UCL
- UCL Institute of Neurology
- Media coverage
Image
- Source: Pixabay
Source
- The Lancet
Media contact
Chris Lane
Tel: +44 (0)20 7679 9222
Email: chris.lane [at] ucl.ac.uk