Many factors have been thought to cause or influence the development and severity of idiopathic scoliosis. This thesis comprises a research programme designed to analyse critically seven of these concomitants popularly believed to be important in the aetiology of idiopathic scoliosis. The first studies comprised pineal gland lesions/ablation, growth hormone treatment and delayed puberty from hypothalamic – pituitary disorders through retrospective clinical studies involving an Australian paediatric population. Initial investigations identified 298 patients in a consecutive unselected series of cases drawn from the Growth Hormone Treatment programmes of three Australian States (Queensland, South Australia and Western Australia) and a consecutive series of 48 cases of pineal lesions drawn from five Australian States (Queensland, New South Wales, Victoria, South Australia and Western Australia). No significant causal link could be established between these factors and the development of idiopathic scoliosis.
Scoliosis, however, was observed to be more prevalent in Turner and other syndromes. The scoliosis observed in Turner syndrome was established to be clinically and radiologically similar to idiopathic scoliosis, with both demonstrating similar subtle radiological irregularities of the vertebral end-plates. The possibility of Turner syndrome being a sound human scientific model to research the aetiology of idiopathic scoliosis arose. Idiopathic scoliosis is developmental and inherited in a familial pattern suggesting genetic influences. Genetic influences are associated with a range of dysmorphic developmental skeletal abnormalities in Turner syndrome, including mesomelic short stature, cubitus valgus, genu valgum, short ring finger metacarpal and Madelung deformity of the wrist. Dysmorphic growth plates are reported with these dysmorphic developmental skeletal abnormalities and are recently reported to be associated with variable expression of the Short Stature on X (SHOX) gene.
Observations of magnetic resonance images of juvenile vertebral growth plates removed during routine idiopathic scoliosis surgery were recorded. Partial growth plate abnormalities were identified on magnetic resonance images, which appeared to be similar to those observed in the spine of a Turner syndrome patient. Histopathological abnormalities of the removed vertebral body growth plates identified disordered columns of chondrocytes in an idiopathic scoliosis patient, resembling dysmorphic change.
Therefore, there was reason to believe that idiopathic scoliosis may be caused by similar genetic influences to those, which caused the other Turner syndrome skeletal abnormalities. Expression of the SHOX gene in the growth plates of idiopathic scoliotic vertebrae was demonstrated to be significantly greater than SHOX expression in congenital scoliosis, providing scientific evidence that genetic influences can be detected at the level of target vertebral body growth plates in scoliosis and that these influences may be associated with a trigger for the development of idiopathic scoliosis.
During the course of the studies, it became apparent that other candidate genes for gene expression studies of the aetiology of idiopathic scoliosis were in a location adjacent to SHOX on the X and Y chromosomes. This locus is responsible for an unusually high rate of mutations, deletions and additions in the genome. ASMT resides close to SHOX on this locus and is responsible for the final phase of synthesis of melatonin, the absence of which is popularly believed to be integrally involved in the development of idiopathic scoliosis. Undetectable ASMT expression was observed in scoliotic vertebral body growth plates, implying low melatonin synthesis.