Rare mutations linked to severe scoliosis

Rare mutations in two genes can drastically elevate children’s chances of developing severe scoliosis, according to recent research.

Children with these mutations are four times more likely to develop severe scoliosis than their peers with normal versions of the genes, scientists from the Washington University School of Medicine in St. Louis have found.

“We have 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,” senior study author ,b>Christina A. Gurnett, MD, PhD, stated in a press release.

There are drugs currently in clinical trials that block a major growth pathway controlled by the mutated genes, fibrillin-1 and fibrillin-2. If the same pathway is involved in scoliosis, doctors may be able to use these drugs to prevent scoliosis in certain children with these mutations, according to the press release.

“We want to create a genetic testing panel that we can use to more accurately predict who will need treatment,” co-author, Matthew Dobbs, MD, stated. “If we can develop effective treatments and apply them early enough, we might one day be able to prevent the need for surgeries.”

The findings appear online in Human Molecular Genetics.

One percent to 3 percent of the general population has some mild curvature of the spine.

In about one in 10,000 children, scoliosis will produce curvature so pronounced that it requires corrective surgery.

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

In 91 patients with acute scoliosis in the study, scientists sequenced the portions of the patients’ DNA that encode proteins.

The most consistently mutated gene in the group was fibrillin-1, which makes a protein important to the tissues that connect many components of the body.

A related gene, fibrillin-2, also often was mutated.