Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity, affecting 1% to 3% of adolescents. (1) 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 becomes rotated axially. Deviation can occur anteriorly (a lordotic deviation) or posteriorly (a kyphotic deviation). 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 rapid onset and produce considerable morbidity, school screenings have been recommended. However, screening remains somewhat controversial, with conflicting guidelines supporting this practice or alternatively suggesting insufficient evidence for this.
Diagnosis 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. (2) The Cobb angle is defined as the angulation measured between the maximally tilted proximal and distal vertebrae of the curve. Curvature is considered mild (less than 25º), moderate (25º to 40º), or severe (more than 40º) in an individual still growing. Once diagnosed, patients must be monitored over several years, usually with serial radiographs for curve progression. If 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 have been published by Lonstein and Carlson (3) and Peterson and Nachemson (4) to help in triage and treatment decision making about patients with AIS. Tan et al. (5) have recently compared a broad array of factors and concluded that using 30 degrees as an endpoint, initial Cobb angle magnitude produces the best prediction of progression outcome.
The familial nature of this disease was noted as early as 1968. (6) About one quarter of patients report a positive family history of disease, and twin studies have consistently supported shared genetic factors. (1) Genome-wide linkage studies have reported multiple chromosomal regions of interest, often not replicated. Ogilvie has recently suggested AIS is a complex polygenic trait. (7) He and colleagues at Axial Diagnostics have published a study evaluating an algorithm using 53 SNP (single nucleotide polymorphisms) markers identified from unpublished genome-wide association studies (GWAS) to identify patients unlikely to exhibit severe progression in curvature versus those at considerable risk for severe progression. The clinical validity of this assay has recently been reported in a retrospective case control cohort study using this algorithm. (2)
The ScoliScore™ AIS prognostic DNA-based test (Axial Biotech, Salt Lake City, UT) is a saliva-based genetic test designed to predict the risk of progression of scoliosis in patients with AIS. The test uses an algorithm incorporating results of testing for 53 SNPs, along with the patient’s presenting spinal curve (Cobb angle) to generate a risk score (ranging from 1 to 200), which can be used qualitatively or quantitatively to predict the likelihood of spinal curve progression. The test is intended for white (Caucasian) patients with a primary diagnosis of AIS between the ages of 9 and 13 years-old with a mild scoliotic curve (defined as <25º).
The ScoliScore™ AIS prognostic DNA-based test has not been approved or cleared by the U.S Food and Drug Administration (FDA) but is being offered as a laboratory-developed test. The laboratory performing this test is accredited by the Centers for Medicare and Medicaid (CMS) under the Clinical Laboratory Improvement Amendments of 1988 (CLIA).
The FDA has indicated an interest in changing its policy for use of enforcement discretion in the oversight of laboratory-developed tests, but the status of this proposed change in policy and the impact of any particular laboratory-developed test are currently unknown.