Not written by me–posted by me–Spine Journal Synopsis at bottom of post
DNA spit test springs girl, 12, from scoliosis brace
msnbc.com updated 12/1/2010 8:45:09 AM ET 2010-12-01T13:45:09
By JoNel Aleccia
Genetic exam is 99 percent accurate in predicting which kids won’t get worse, study says
When Marissa Levy learned she’d have to wear a back brace 23 hours a day, the New York seventh-grader thought it might as well be a prison sentence.
For four months last year, she railed against the padded hard plastic shell that was strapped to her torso as a treatment for scoliosis, the disease that was slowly curving her spine.
“It just seemed to me like this big, heavy thing,” said Marissa, now 12, who dreaded gym class and tried to hide the brace, which ran from her hips to neck, under oversized sweatshirts. “I didn’t like it at all.”
But in December, just when Marissa and her mother, Tara Melgar, thought they couldn’t take another day of tears and arguments, doctors decided to try a new genetic test that researchers say can tell which young scoliosis patients won’t get worse, and likely won’t require more treatment.
Marissa spit into a tube, and her saliva was sent off for DNA testing. Three weeks later, her mom got a phone call: Marissa didn’t need the brace after all.
“It was unbelievable to think of,” said Melgar, 39, of Oceanside, N.Y., who suffered from scoliosis herself. “I felt horrible for all those months of fighting with her and torturing her.”
Marissa quickly tossed her brace into the trash, becoming one of the first youngsters to benefit from the $2,500 DNA test aimed at saving thousands of adolescents from the emotional and physical toll of braces, X-rays, and repeated exams.
99 percent accurate test
New research published in the journal Spine reports that the test is 99 percent accurate in predicting which sufferers of adolescent idiopathic scoliosis, or AIS, are least likely to develop curves serious enough to require surgery.
“We knew there was a genetic component,” said Dr. Baron S. Lonner, director of Scoliosis and Spine Associates of New York, who treated Marissa.
“This is the first prognostic test in orthopedics that allows us to tell through the DNA.”
The test, dubbed SCOLISCORE, also can indicate accurately when patients have an intermediate or high risk, but because those kids need intensive monitoring, the study focused on identifying those with lowest risk.
The test uses calculations based on 53 genetic markers associated with scoliosis progression to score a patient’s risk of developing a spinal curve of more than 40 degrees.
On a scale of 1 to 200, a score of 50 or less is classified as a low risk, a score of 51 to 180 is an intermediate risk, and a score of 181 to 200 is a high risk.
In Marissa’s case, her score was 11.
“When they told me how unbelievably low her number was, it was amazing,” Melgar, Marissa’s mom, said.
Marissa is among the 2 percent to 4 percent of all youngsters older than 10 diagnosed with AIS, including about 30,000 who require braces and 18,000 who need spinal fusion surgery each year.
It’s not clear what causes the disorder, which is detected in kids who have a lateral curvature of the spine that’s greater than 10 degrees. Boys and girls are diagnosed equally with AIS, but girls typically develop more severe conditions.
The diagnosis often causes great anxiety for kids and their parents, especially for the estimated 10 percent of patients who might need braces for months or years. “Almost 100 percent of the time, there are tears,” Lonner said.
Risk is usually low, but docs treat anyway
Most newly diagnosed AIS patient actually have a low risk of developing a severe curve, but they’re often treated aggressively out of fear of missing the window of growth for treatment, Lonner said.
“It’s kind of like tethering a sapling that’s growing crooked,” Lonner said.
In the new Spine study, researchers studied DNA samples and medical records of nearly 700 patients from more than 100 clinical sites across the U.S.
Using the test, about 75 percent of the patients were accurately identified as low risk, with a 1 percent chance of progressing to a surgical curve. About 24 percent were intermediate risk and 1 percent were high risk.
Interestingly, the results apply only to white patients because researchers couldn’t get a robust sample of other races, although they’re working on it, said Dr. Kenneth Ward, chairman of Axial Biotech.
Study authors and doctors like Lonner, who contributed to the research, expect to benefit financially from development of the new test, which was developed by Axial Biotech Inc.
The $2,500 cost of the test is covered by some insurance plans, but the company has been footing the bill for some, a spokeswoman said.
However, spine specialists with no stake in the product also agree that it’s helpful, especially for identifying kids who are at definite low risk or definite high risk of severe curves.
“It’s an additional tool,” said Dr. Michael R. Marks, a spokesman for the American Academy of Orthopaedic Surgeons and a surgeon in Norwalk, Conn.
“The kids who score low or the kids who score very high, they’re no brainers.”
But the kids in the middle, those who score at the borders of risk, remain problematic — and the test doesn’t solve that, Marks said. So far, his practice has used the new test on four youngsters, all of whom turned up with scores in the middle range.
But for kids like Marissa Levy and their families, a diagnosis of exclusion is just fine.
In the months since ditching the brace, Marissa’s curve has receded from about 24 degrees to 10 degrees, Lonner said. It’s not clear why she improved so much, although natural regression does occur, he said.
Marissa’s mom says her only regret is that she didn’t get the test done sooner.
“It could have saved so much heartache as a parent and a child,” Tara Melgar said.
SPINE Volume 35, Number 25, pp E1455–E1464 2010, Lippincott Williams & Wilkins
Validation of DNA-Based Prognostic Testing to Predict Spinal Curve Progression in Adolescent
Idiopathic Scoliosis-Kenneth Ward, MD,* James W. Ogilvie, MD,* Marc V. Singleton, MS,*
Rakesh Chettier, MS,* Gordon Engler, MD,† and Lesa M. Nelson, BS*
Study Design. Validation of a prognostic DNA marker panel.
Objective. The goals of this study were to develop and test the negative predictive value of a prognostic DNA test for adolescent idiopathic scoliosis (AIS) and to establish clinically meaningful endpoints for the test.
Summary of Background Data. Clinical features do not adequately predict which children diagnosed with minimal or mild AIS will have the progressive form of the
disease; genetic markers associated with curve progression might offer clinically useful prognostic insights.
Methods. Logistic regression was used to develop an algorithm to predict spinal curve progression incorporating genotypes for 53 single nucleotide polymorphisms
and the patient’s presenting spinal curve (Cobb angle).
Three cohorts with known AIS outcomes were selected to reflect intended-use populations with various rates of AIS progression: 277 low-risk females representing a screening cohort, 257 females representing higher risk patients followed at referral centers, and 163 high risk males.
DNA was extracted from saliva, and genotypes were determined using TaqMan assays. AIS Prognostic Test scores ranging from 1 to 200 were calculated.
Results. Low-risk scores (<41) had negative predictive values of 100%, 99%, and 97%, respectively, in the tested populations.
In the risk model, we used cutoff scores of 50 and 180 to identify 75% of patients as low-risk (<1% risk of progressing to a surgical curve), 24% as intermediate risk, and 1% as high-risk.
Conclusion. Prognostic testing for AIS has the potential to reduce psychological trauma, serial exposure to diagnostic radiation, unnecessary treatments, and direct
and indirect costs-of-care related to scoliosis monitoring in low-risk patients.
Further improvements in test performance are expected as the optimal markers for each locus are identified and the underlying biologic pathways are better understood. The validity of the test applies only to white AIS patients; versions of the test optimized for AIS patients of other races have yet to be developed.