The aetiology of the three-dimensional spinal deformity of idiopathic scoliosis (IS) is unknown. Progressive adolescent idiopathic scoliosis (AIS) that mainly affects girls is generally attributed to relative anterior spinal overgrowth from a mechanical mechanism (torsion) during the adolescent growth spurt. Established biological risk factors to AIS are growth velocity and potential residual spinal growth assessed by maturity indicators. Spine slenderness and ectomorphy in girls are thought to be risk factors for AIS. Claimed biomechanical susceptibilities are (1) a fixed lordotic area and hypokyphosis and (2) concave periapical rib overgrowth. MRI has revealed neuroanatomical abnormalities in approximately 20% of younger children with IS. A neuromuscular cause for AIS is probable but not established. Possible susceptibilities to AIS in tissues relate to muscles, ligaments, discs, skeletal proportions and asymmetries, the latter also affecting soft tissues (e.g. dermatoglyphics). AIS is generally considered to be multi-factorial in origin. The many anomalies detected, particularly left-right asymmetries, have led to spatiotemporal aetiologic concepts involving chronomics and the genome altered by nurture without the necessity for a disease process. Genetic susceptibilities defined in twins are being evaluated in family studies; polymorphisms in the oestrogen receptor gene are associated with curve severity. A neurodevelopmental concept is outlined for the aetiology of progressive AIS. This concept involves lipid peroxidation and, if substantiated, has initial therapeutic potential by dietary anti-oxidants. Growth saltations have not been evaluated in IS.

Genetic factors are believed to play an important role in the etiology of adolescent idiopathic scoliosis (AIS). Discordant findings for monozygotic (MZ) twins with AIS show that environmental factors including different intrauterine environments are important in etiology, but what these environmental factors may be is unknown. Recent evidence for common chronic non-communicable diseases suggests epigenetic differences may underlie MZ twin discordance, and be the link between environmental factors and phenotypic differences. DNA methylation is one important epigenetic mechanism operating at the interface between genome and environment to regulate phenotypic plasticity with a complex regulation across the genome during the first decade of life. The word exposome refers to the totality of environmental exposures from conception onwards, comprising factors in external and internal environments. The word exposome is used here also in relation to physiologic and etiopathogenetic factors that affect normal spinal growth and may induce the deformity of AIS. In normal postnatal spinal growth we propose a new term and concept, physiologic growth-plate exposome for the normal processes particularly of the internal environments that may have epigenetic effects on growth plates of vertebrae. In AIS, we propose a new term and concept pathophysiologic scoliogenic exposome for the abnormal processes in molecular pathways particularly of the internal environment currently expressed as etiopathogenetic hypotheses; these are suggested to have deforming effects on the growth plates of vertebrae at cell, tissue, structure and/or organ levels that are considered to be epigenetic. New research is required for chromatin modifications including DNA methylation in AIS subjects and vertebral growth plates excised at surgery. In addition, consideration is needed for a possible network approach to etiopathogenesis by constructing AIS diseasomes. These approaches may lead through screening, genetic, epigenetic, biochemical, metabolic phenotypes and pharmacogenomic research to identify susceptible individuals at risk and modulate abnormal molecular pathways of AIS. The potential of epigenetic-based medical therapy for AIS cannot be assessed at present, and must await new research derived from the evaluation of epigenetic concepts of spinal growth in health and deformity. The tenets outlined here for AIS are applicable to other musculoskeletal growth disorders including infantile and juvenile idiopathic scoliosis.

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