Scoliosis is defined by an abnormal, sideways curvature of the spine, often presenting in a C- or S-shape when viewed from the back. This spinal deformity also involves a rotational component, making it a complex, three-dimensional change to the body’s structure. Affecting an estimated 2 to 3% of the global population, the condition typically begins during the rapid growth years of adolescence.
Classifying Scoliosis: When Genetics Matters Most
Scoliosis is an umbrella term encompassing several types, each with a different underlying cause. The condition is broadly categorized based on its origin, including congenital, neuromuscular, and idiopathic forms. Congenital scoliosis arises from a malformation of the vertebrae during fetal development. Neuromuscular scoliosis is secondary to conditions that affect the muscles and nerves supporting the spine, such as cerebral palsy or muscular dystrophy.
The vast majority of cases, approximately 80%, are classified as idiopathic, meaning the cause is unknown. This category is subdivided based on the patient’s age at onset, with Adolescent Idiopathic Scoliosis (AIS) being the most prevalent form, diagnosed in children between the ages of 10 and 18. Scientific investigation into a genetic link focuses almost exclusively on AIS, as other types have established causes related to birth defects or neurological illnesses. Therefore, discussions about the heritability of a spinal curve primarily address the factors contributing to AIS.
Evidence for the Genetic Link
Decades of research using family and twin studies show that a genetic predisposition underlies the development of AIS. The condition exhibits familial aggregation, meaning it occurs more frequently within certain families than in the general population. Up to 50% of individuals diagnosed with AIS report a family history of the condition.
The risk for a first-degree relative developing scoliosis is substantially higher than the 2 to 3% risk seen in the general population, with recurrence rates reported between 11% and 16%. Twin studies offer a compelling argument for inheritance by comparing identical (monozygotic) twins, who share 100% of their DNA, with fraternal (dizygotic) twins, who share about 50%. Identical twins show a significantly higher rate of concordance for AIS compared to fraternal twins, sometimes reaching 73% versus 36%.
This inheritance pattern does not fit the simple model of a single gene being passed down, but rather a complex system known as polygenic inheritance. In this model, multiple genes, each contributing a small risk, interact to influence the likelihood of developing the spinal curve. This complexity explains the variable expression of the condition, where some family members may have a mild curve while others are severely affected.
Current Research on Susceptibility Genes
Modern genetic techniques, particularly Genome-Wide Association Studies (GWAS), have been instrumental in identifying specific regions of the genome associated with AIS risk. These studies scan the entire genome of affected individuals and healthy controls to pinpoint variations in DNA, called single nucleotide polymorphisms (SNPs), that occur more frequently in those with scoliosis. This work has led to the discovery of several susceptibility loci, or locations on chromosomes, that influence the condition.
Notable genes identified through GWAS include LBX1 and GPR126, which have been consistently replicated across different populations. The LBX1 gene is involved in somatosensory function and neural development, suggesting that genetic risk may relate to the nervous system’s control over posture and balance. The GPR126 gene is linked to the delayed ossification of the developing spine and the myelination process, pointing toward effects on growth and nerve conduction velocity.
The susceptibility loci identified suggest that the genetic risk for AIS involves pathways related to bone formation, growth regulation, and the central nervous system. However, the identified genetic variations only account for a portion of the total heritability of AIS. This reinforces the belief that AIS is a multifactorial condition, where genetic risk factors must interact with environmental factors—which are still largely unknown—to fully manifest the spinal curve.
Implications for Risk and Family Screening
The established genetic link has practical implications for assessing an individual’s risk and guiding clinical management. Given the elevated risk for first-degree relatives, family history is an important factor in determining the need for proactive screening. While the general population risk for AIS is low, the risk to a child or sibling of an affected individual is higher.
Because the severity of a parent’s or sibling’s curve does not influence the risk or severity in other family members, regular visual screening is recommended for all high-risk children. This screening, often performed by pediatricians or in schools during the rapid growth phase (ages 10 to 15), typically involves the Adam’s forward bend test. Identifying the curve early is beneficial because intervention, such as bracing, is most effective while the spine is still growing.
New genetic insights are paving the way for future diagnostic and prognostic tools, such as tests that predict the likelihood of curve progression. Although the clinical utility of current genetic tests is under investigation, continued research into the polygenic basis of AIS may eventually lead to targeted, non-invasive treatments that influence the molecular pathways responsible for the condition.