Rare Genetic Mutations Increase Risk of Severe Scoliosis

Children who suffer from two genes linked to rare genetic mutations are four times more likely to develop a severe type of scoliosis than peers, according to a recent study published in the journal Human Molecular Genetics.

Researchers at the Washington University School of Medicine in St. Louis, Mo., found that these genetic factors that predisposed students to develop the s-shaped curves in their spines resulted in such a dramatic problem that surgery was oftentimes needed.

"We've had a difficult time finding ways to predict who will develop severe scoliosis, and these newly identified mutations have the potential to be very helpful," said senior author Christina A. Gurnett, MD, PhD, in a news release.

Doctors are currently working on several clinical trials that help block major pathways involved in these rare mutations, fibrillin-1 and fibrillin-2, control. If the same pathways are involved in scoliosis, doctors may be able to use the drugs to prevent the health issue in some children who carry the mutations--an estimated one in 10,000 children who require corrective surgery for their scoliosis.

"These children often don't have any curvature of the spine early in adolescence, but then they go through a growth spurt, and that's when the curve appears," said Gurnett, associate professor of neurology. "Others have tried to predict severe disease using gender, age of onset and type of spine curve but haven't been very successful."

The research team examined 91 patients with acute scoliosis. Scientists sequenced portions of their DNA and found that the most consistently mutated gene in the group was fibrillin-1--a protein important for with regards to the connective tissues found in the body. A related gene, fibrillin-2, was also often found to be mutated. 

In an additional gene sequencing of 852 patients with scoliosis and 669 subjects with healthy spines, the researchers found specific mutations with both genes. This increased the risk of severe scoloios up to four times. 

Clinical drug trials are currently underway to determine if certain drugs that block TGF-beta can help treat the disorder.