Medical Policy

Subject: DNA-Based Testing for Adolescent Idiopathic Scoliosis
Document #: GENE.00024 Current Effective Date:    03/29/2017
Status: Reviewed Last Review Date:    02/02/2016


This document addresses deoxyribonucleic acid (DNA)-based testing for adolescent idiopathic scoliosis (AIS) (for example, ScoliScore [Transgenomic, Inc., Omaha, NE]). ScoliScore is a saliva-based genetic test designed to predict the risk of AIS progression.

Position Statement

Investigational and Not Medically Necessary:

DNA-based prognostic testing for adolescent idiopathic scoliosis (AIS) is considered investigational and not medically necessary.


Controversy exists about the value of both screening and treatment of AIS. However, once an adolescent is diagnosed with AIS, the condition is frequently closely followed. In cases with significant progression of curvature, both medical (for example, bracing) and surgical interventions can be considered. DNA-based saliva testing has been proposed as a method to predict the risk of progression in those with a primary diagnosis of AIS between the ages of 9 and 13 years with a mild scoliotic curve (defined as less than 25º).

Ogilvie and colleagues (2011), of Axial Biotech, evaluated an algorithm using 53 single nucleotide polymorphisms (SNP) markers identified from unpublished genome-wide association studies (GWAS) to identify individuals unlikely to exhibit severe progression of scoliosis curvature versus those at considerable risk for severe progression. The authors suggested that AIS is a complex polygenetic trait and additional research is needed in non-Caucasian genetics.

Ward and colleagues (2010), in an industry-sponsored clinical study, attempted to validate a DNA-based prognostic test to predict spinal curve progression in AIS. This test involved the use of a proprietary algorithm to integrate information from 53 SNPs identified as exhibiting an association with AIS. Clinical validation of the DNA-based prognostic test was performed in a retrospective analysis of cases pre-selected by curvature severity (mild, moderate, or severe) and assigned into three cohorts identified as: 1) a screening cohort of 277 white females; 2) a spinal surgery practice cohort of 257 white females; and 3) a cohort of 163 high risk males. Study results demonstrated that low risk scores (less than 41) had negative predictive values of 100%, 99% and 97%, respectively, in the tested populations. A significant study limitation was that small sample sizes limited validation to Caucasians only.

A subsequent GWAS (Sharma, 2011) evaluated 327,000 SNPs from 419 families with AIS and concluded that no single locus contributes predominantly to AIS risk. The authors also noted that further study in larger cohorts is needed to confirm their findings.

Roye and colleagues (2012) assessed ScoliScore results of 91 individuals and reported a positive correlation between Cobb angle and ScoliScore (r=0.581, p<0.001). However, ScoliScore appeared to provide information very different from that observed using standard risk score, with a marked increase in low-risk individuals and decrease in those who were at high-risk. No clinical endpoints were examined in association with classification results, and the interpretation of results was unclear.

Ogura and colleagues (2013) performed a replication study to determine whether the association of 53 SNPs with curve progression previously reported in Caucasians with AIS could be replicated in Japanese individuals with AIS. A total of 2117 Japanese subjects were initially recruited and 1714 were evaluated. Those with a 10 degree or more Cobb angle of scoliosis curves were divided into progression (n=600) and non-progression (n=1114) groups. The association of 53 SNPs with curve progression was assessed by comparing risk allele frequencies between the two groups. The authors concluded that the 53 SNPs previously used in the prognostic test for Caucasians were not replicated in their study of Japanese and replication studies in other ethnic groups are necessary.

In 2015, Tang and colleagues performed a French-Canadian replication study of genomic data to determine whether the 53 SNPs previously associated with spinal deformity progression in an American Caucasian cohort, were associated similarly in the French-Canadian population. A total of over 1.4 million SNPs from 667 subjects with AIS (122 males and 545 females) and 901 controls (425 males and 476 females) were evaluated. The frequency of each SNP among all AIS subjects was compared to those of all controls. None of the SNPs used in ScoliScore were found to be associated with AIS curve progression or curve occurrence in the French-Canadian population. The authors concluded that as demonstrated in an earlier study of a Japanese cohort (Ogura, 2013), no significant association to AIS generally or to curve severity was found in the French-Canadian population.

A systemic review and meta-analysis by Noshchenko and colleagues (2015) evaluated published literature to assess both the evidence and efficacy of predictors for progressive AIS. Of the 25 studies included in the review, all demonstrated a statistically significant or borderline association between severity or progression of AIS with certain characteristics such as: an increase of the Cobb angle or axial rotation during brace treatment, decrease of the rib-vertebral angle at the apical level of the convex side during brace treatment, initial Cobb angle severity, osteopenia, age below13 years at diagnosis, premenarche status, skeletal immaturity, thoracic deformity, brain stem vestibular dysfunction, and multiple indices combining radiographic, demographic, and physiologic characteristics. Specific to single nucleotide polymorphisms such as those included in the ScoliScore, the authors reported that their review did not reveal any methods for the prediction of progression in AIS that could be recommended for clinical use as diagnostic criteria. They also noted that further research is needed in this field.

Roye and colleagues (2015) reported on a retrospective cohort study of 126 subjects with AIS from two U.S. centers. A progression group and a non-progression group were identified. There were 113 female subjects and 13 male subjects. Risk levels and ScoliScore values were compared between the two groups. No significant ScoliScore difference was reported between subjects with and without curve progression. Additionally, there was no significant difference in curve progression between subjects with high-risk scores as compared to those with low-risk scores. The positive predictive value of the test was 0.27 (95% confidence interval [CI], 0.09 to 0.55) and the negative predictive value was 0.87 (95% CI, 0.69 to 0.96). The authors concluded "the results of this first external validation of the ScoliScore suggest that the test has limited utility in our population."

Xu and colleagues (2016) performed a retrospective review to assess the association of the ScoliScore test with AIS curve progression in Chinese adolescents. A total of 670 Chinese Han females with AIS who visited a single clinic between May 2004 and December 2014 were included in the study. Of these, 313 subjects were assigned to the non-progression group and the other 357 assigned to the progression group. The allele frequencies of 53 SNPS included in the ScoliScore were compared between subjects with progressive curve and those with non-progressive curve. Of the 53 SNP's, only two were found to have significantly different allele frequencies between the non-progression and progression groups. There were no allele frequency differences between the two groups for the other 51 SNP's. The authors concluded that ScoliScore is not a reliable means to predict the curve progression of AIS in Chinese Han population. Additionally, they noted that the role of the test in other populations cannot be totally excluded and additional replication studies are needed.

A small retrospective study by Bohl and colleagues (2016) correlated ScoliScore results to bracing outcomes of 16 subjects with AIS from a single U.S. provider. The 16 subjects were followed for an average of 2.3 years after Providence brace application. A total of 8 subjects progressed to more than 45 degrees, while 8 subjects did not. The mean ScoliScore of those who progressed to more than 45 degrees was noted to be higher than among those who did not (176 versus 112). Study limitations include a small sample size.

At the current time, there is a lack of evidence in the peer-reviewed medical literature to confirm the clinical utility and validity of DNA-based testing for AIS. There is no direct evidence demonstrating that the use of this test results in changes in management of AIS that would improve outcomes. In addition, the value of early identification and intervention(s) for individuals at risk for progression of AIS is unclear. Further research of both clinical utility and validity is needed.


Adolescent idiopathic scoliosis (AIS) is a disease of unknown etiology that causes mild to severe spinal deformity in approximately 1 to 3% of adolescents. DNA-based testing for AIS (ScoliScore) is performed by collecting a saliva sample during a physician's office visit. It is proposed that results of the testing, combined with other clinical information, can be used to define a personalized treatment plan for the child.

ScoliScore uses an algorithm incorporating results of testing for 53 SNPs, along with the individual's presenting spinal curve (Cobb angle) to generate a risk score (ranging from 1 to 200). This test is intended for use in Caucasians with a primary diagnosis of AIS between 9 and 13 years of age with mild scoliotic curve (defined as less than 25º).

ScoliScore AIS testing is an in-house developed laboratory service. The laboratory performing this test is accredited by the Centers for Medicare and Medicaid (CMS) under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Pre-market approval from the FDA is not required.


The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

0004M Scoliosis, DNA analysis of 53 single nucleotide polymorphisms (SNPs), using saliva, prognostic algorithm reported as a risk score
ScoliScore™, Transgenomic
ICD-10 Diagnosis  
  All diagnoses

Peer Reviewed Publications:

  1. Bohl DD, Telles CJ, Ruiz FK, et al. A genetic test predicts providence brace success for adolescent idiopathic scoliosis when failure is defined as progression to greater than 45 degrees. J Spinal Disord Tech. 2016; 29(3):E146-E150.
  2. Hresko MT. Clinical practice. Idiopathic scoliosis in adolescents. N Engl J Med. 2013; 368(9):834-841.
  3. Noshchenko A, Hoffecker L, Lindley EM, et al. Predictors of spine deformity progression in adolescent idiopathic scoliosis: A systematic review with meta-analysis. World J Orthop. 2015; 6(7):537-558.
  4. Ogilvie J. Adolescent idiopathic scoliosis and genetic testing. Curr Opin Pediatr. 2010; 22(1):67-70.
  5. Ogilvie JW. Update on prognostic genetic testing in adolescent idiopathic scoliosis (AIS). J Pediatr Orthop. 2011; 31(1 Suppl):S46-48.
  6. Ogura Y, Takahashi Y, Kou I, et al. A replication study for association of 53 single nucleotide polymorphisms in a scoliosis prognostic test with progression of adolescent idiopathic scoliosis in Japanese. Spine (Phila Pa 1976). 2013; 38(16):1375-1379.
  7. Roye BD, Wright ML, Matsumoto H, et al. An independent evaluation of the validity of a DNA-based prognostic test for adolescent idiopathic scoliosis. J Bone Joint Surg Am. 2015; 97(24):1994-1998.
  8. Roye BD, Wright ML, Williams BA, et al. Does ScoliScore provide more information than traditional clinical estimates of curve progression? Spine (Phila Pa 1976). 2012; 37(25):2099-2103.
  9. Sharma S, Gao X, Londono D, et al. Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes. Hum Mol Genet. 2011; 20(7):1456-1466.
  10. Tang QL, Julien C, Eveleigh R, et al. A replication study for association of 53 single nucleotide polymorphisms in ScoliScoreTM test with adolescent idiopathic scoliosis in French-Canadian population. Spine (Phila Pa 1976). 2015; 40(8):537-543.
  11. Ward K, Ogilvie JW, Singleton MV, et al. Validation of DNA-based prognostic testing to predict spinal curve progression in adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2010; 35(25):E1455-1464.
  12. Xu L, Qin X, Sun W, et al. Replication of association between 53 single nucleotide polymorphisms in a DNA-based diagnostic test and AIS progression in Chinese Han population. Spine (Phila Pa 1976). 2016; 41(4):306-310.

DNA-Based Testing for Adolescent Idiopathic Scoliosis

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History




Reviewed 02/02/2017 Medical Policy & Technology Assessment Committee (MPTAC) review. Rationale and References sections updated.
Reviewed 05/05/2016 MPTAC review. Description, Rationale and Reference sections updated. Removed ICD-9 codes from Coding section.
Reviewed 05/07/2015 MPTAC review. Description, Rationale and Reference sections updated.
Reviewed 05/15/2014 MPTAC review. Rationale and Reference sections updated.
Reviewed 05/09/2013 MPTAC review. Rationale and Reference sections updated. Updated Coding section with 07/01/2013 CPT changes.
  01/01/2013 Updated Coding section with 01/01/2013 CPT changes; removed 83890-83914 deleted 12/31/2012.
New 05/10/2012 MPTAC review. Initial document development.