Imma Perfetto
Cosmos science journalist
Researchers have made significant headway towards determining the genetic risk factors driving spina bifida, a birth defect which can cause severe disability.
The findings of a Nature study open new avenues to diagnose, treat, and potentially even prevent the condition, which effects roughly 1 in every 3,000-10,000 births.
“Our research identifies specific steps in embryogenesis that contribute to spina bifida,” says Dr Joseph Gleeson, senior author of the new Nature study and professor at Rady Children’s Institute for Genomic Medicine and the University of California, San Diego.
“This is a major step forward in understanding why this condition occurs and how we might one day prevent it.”
Spina bifida – meaning “split spine” – develops in the first 6 weeks of pregnancy when the neural tube, which eventually becomes the spine and spinal cord, doesn’t form properly. This leaves parts of the spinal cord exposed and easily damaged.
Depending on the severity of the condition, individuals can have mild to severe lifelong neuromotor disability, including lower limb weakness, problems with bladder and bowel control, and learning and intellectual disabilities.
While folic acid deficiency has been established as an important risk factor for spina bifida, with supplementation reducing the disease’s burden, its underlying causes are still poorly understood.
The researchers set out to identify whether “de novo mutations” – new mutations in the offspring which are not inherited from the parents – contribute to the disease.
They established the Spina Bifida Sequencing Consortium to collect genetic and health data from babies born with the most serious form of spina bifida (meningomyelocele), and their parents.
It took a decade to collect enough data (from 851 parent-child trios) to identify damaging mutations in 186 genes which contribute to the risk of developing spina bifida. The mutations, which were present in nearly a quarter of the patients, impact how cells within the embryo connect to one another.
Spina bifida is most often identified during prenatal ultrasound, but the study’s first author, Dr Yoo-Jin Ha of UC San Diego and Korea’s Yonsei University College of Medicine, says the results can now be used to “develop new screening tools to achieve more accurate and earlier diagnosis, and possibly predict the degree of disability.”
By identifying critical pathways required for neural tube closure in human embryogenesis, the new discovery brings scientists a step closer to one day being able to intervene before the condition develops.
“Currently, foetal surgery to correct the condition after it starts has shown promise in reducing disease severity,” says Gleeson.
“While more research is needed, our findings provide a new foundation for exploring possible prevention.”
