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L.2.04.452
Adolescent idiopathic scoliosis (AIS) is a disease of unknown etiology that causes mild-to-severe spinal deformity in approximately 1% to 3% of adolescents. While there is controversy about the value of both screening and treatment, once diagnosed, patients are frequently closely followed. In cases with significant progression of curvature, both medical (bracing) and surgical (spinal fusion) interventions are considered. The ScoliScore AIS prognostic DNA-based test uses an algorithm incorporating results of testing for 53 single-nucleotide variants (SNVs), along with the patient’s presenting spinal curve (Cobb angle), to generate a risk score (range, 1 to 200), which can be used qualitatively or quantitatively to predict the likelihood of spinal curve progression.
Adolescent Idiopathic Scoliosis
Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity, affecting 1% to 3% of adolescents. This disease, of unknown etiology, occurs in otherwise healthy children with the onset of, and highly correlated with, the adolescent growth spurt. The vertebrae become misaligned such that the spine deviates from the midline laterally and rotates axially. The deviation can occur anteriorly (a lordotic deviation), posteriorly (a kyphotic deviation), or laterally. Although AIS affects females and males in a nearly 1:1 ratio, progression to severe deformity occurs more often in females. Because the disease can have a rapid onset and produce considerable morbidity, school screenings have been recommended. However, screening remains somewhat controversial, with conflicting guidelines supporting and not supporting this practice.
DiagnosisDiagnosis is established by radiologic observation in adolescents (age 10 years until the age of skeletal maturity) of a lateral spine curvature of 10 degrees or more, as measured using the Cobb angle. The Cobb angle is defined as the angle measured between the maximally tilted proximal and distal vertebrae of the curve. The curvature is considered mild (less than 25º), moderate (25º to 40º), or severe (more than 40º) in a patient still growing. Once diagnosed, patients must be monitored over several years, usually with serial radiographs for curve progression.
TreatmentIf the curve progresses, spinal bracing is the generally accepted first-line treatment. If the curve progresses in spite of bracing, spinal fusion may be recommended.
Curve progression has been linked to a number of factors, including sex, curve magnitude, patient age, and skeletal maturity. Risk tables, by Lonstein and Carlson and Peterson and Nachemson, help in triage and treatment decision making about patients with AIS. Tan and colleagues compared a broad array of factors and concluded that using 30º as an end point, initial Cobb angle magnitude produces the best prediction of progression outcome.
Genetic Associations and Scoliosis
The familial nature of this disease was noted as early as 1968. About one-quarter of patients report a positive family history of the disease, and twin studies have consistently supported shared genetic factors. Genome-wide linkage studies have reported multiple chromosomal regions of interest, often not replicated. Ogilvie has suggested AIS is a complex polygenic trait. Ogilvie and colleagues at Axial Diagnostics published a study evaluating an algorithm using 53 single-nucleotide variant (SNV) markers identified from unpublished genome-wide association studies to differentiate patients unlikely to exhibit severe progression in curvature from those at considerable risk for severe progression. The clinical validity of this assay was reported in a retrospective case-control cohort study using this algorithm.
ScoliScore AIS
The ScoliScore AIS prognostic DNA-based test (Transgenomic), which uses an algorithm incorporating results of testing for 53 SNVs, along with the patient’s presenting spinal curve (Cobb angle), to generate a risk score (range, 1 to 200), was used qualitatively or quantitatively to predict the likelihood of spinal curve progression. The test is intended for white (Caucasian) patients, ages 9 to 13 years, with a primary diagnosis of AIS with a mild scoliotic curve (defined as <25°).
The development and validation of the ScoliScore SNV-based prognostic algorithm were described in 2010 by Ward and colleagues in an industry-sponsored study. The prognostic algorithm was developed in a cohort of 2,192 female patients from prior studies. Candidate genes were selected based on previous genome-wide association studies data from the same investigators. The independent effect of each SNV and of clinical factors (initial Cobb angle) and all gene-gene interaction terms were tested in a stepwise logistic regression using a backward-selection procedure, and then using a forward-selection procedure. The final predictive model included 53 SNV markers, multiple gene-gene interaction terms, and the patient’s initial Cobb angle. Prediction probabilities were converted to a numeric score ranging from 1 to 200. A priori, low-risk of progression was determined to be less than 1%; from the generation cohort, a score of less than 41 was selected as an initial cutoff.
Since publication of the Ward et al (2010) study, subsequent clinical studies were unable to replicate the association of the 53 genetic markers with progression of AIS.
The ScoliScore™ AIS Prognostic Test was originally developed by Axial Biotech with test rights acquired by Transgenomic in 2013. In 2015, Transgenomic divested its Genetic Assays & Platforms Business Unit to ADSTEC Corp. In June 2017, Transgenomic was acquired by Precipio Diagnostics in a reverse merger transaction. It appears that the test is no longer commercially available; the ScoliScore™ AIS Prognostic Test is not listed as available on the Precipio Diagnostics website.
Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Laboratories that offer laboratory-developed tests must be licensed by the Clinical Laboratory Improvement Amendments for high-complexity testing.To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.
Related medical policies are –
DNA-based prognostic testing for adolescent idiopathic scoliosis is considered investigational.
None
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
Genetic Counseling
Experts recommend formal genetic counseling for patients who are at risk for inherited disorders and who wish to undergo genetic testing. Interpreting the results of genetic tests and understanding risk factors can be difficult for some patients; genetic counseling helps individuals understand the impact of genetic testing, including the possible effects the test results could have on the individual or their family members. It should be noted that genetic counseling may alter the utilization of genetic testing substantially and may reduce inappropriate testing. Genetic counseling should be performed by an individual with experience and expertise in genetic medicine and genetic testing methods.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
11/17/2011: Approved by Medical Policy Advisory Committee.
09/27/2012: Policy reviewed; no changes.
01/14/2013: Added the following new 2013 CPT codes to the Code Reference section: 81479.
11/06/2013: Policy reviewed; no changes.
09/03/2014: Policy reviewed; description updated. Policy statement unchanged. Removed deleted CPT codes 83891, 83898, 83903, and 83912 from the Code Reference section.
07/13/2015: Code Reference section updated for ICD-10.
11/03/2015: Policy description updated regarding tests. Policy statement unchanged. Investigative definition updated in policy guidelines section.
06/06/2016: Policy number A.2.04.74 added.
04/04/2017: Policy description updated regarding the ScoliScore test. Policy statement unchanged. Policy Guidelines updated to add genetic counseling information. Code Reference section updated to add CPT code 0004M.
02/06/2018: Policy description updated regarding the ScoliScore AIS test. Policy statement unchanged. Policy Guidelines updated regarding genetic counseling information.
02/18/2019: Policy reviewed; no changes.
02/11/2020: Policy reviewed; no changes.
03/30/2021: Policy description updated regarding the ScoliScore™ AIS Prognostic Test. Policy statement unchanged.
03/27/2023: Policy reviewed. Policy statement unchanged. Policy revised to change the medical policy number from "A.2.04.74" to "L.2.04.452."
04/26/2024: Policy reviewed; no changes.
03/28/2025: Policy reviewed; no changes.
Blue Cross Blue Shield Association policy # 2.04.74
Code Number | Description |
CPT-4 | |
0004M | Scoliosis, DNA analysis of 53 single nucleotide polymorphisms (SNPs), using saliva, prognostic algorithm reported as a risk score |
81479 | Unlisted molecular pathology procedure |
HCPCS | |
ICD-10 Procedure | |
ICD-10 Diagnosis |
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