Whither the etiopathogenesis (and scoliogeny) of adolescent idiopathic scoliosis? Incorporating presentations on scoliogeny at the 2012 IRSSD and SRS meetings

R Geoffrey Burwell, Peter H Dangerfield, Alan Moulton, Theodoros B Grivas, Jack CY Cheng

This paper aims to integrate into current understanding of AIS causation, etiopathogenetic information presented at two Meetings during 2012 namely, the International Research Society of Spinal Deformities (IRSSD) and the Scoliosis Research Society (SRS). The ultimate hope is to prevent the occurrence or progression of the spinal deformity of AIS with non-invasive treatment, possibly medical. This might be attained by personalised polymechanistic preventive therapy targeting the appropriate etiology and/or etiopathogenetic pathways, to avoid fusion and maintain spinal mobility. Although considerable progress had been made in the past two decades in understanding the etiopathogenesis of adolescent idiopathic scoliosis (AIS), it still lacks an agreed theory of etiopathogenesis. One problem may be that AIS results not from one cause, but several that interact with various genetic predisposing factors. There is a view there are two other pathogenic processes for idiopathic scoliosis namely, initiating (or inducing), and those that cause curve progression. Twin studies and observations of family aggregation have revealed significant genetic contributions to idiopathic scoliosis, that place AIS among other common disease or complex traits with a high heritability interpreted by the genetic variant hypothesis of disease. We summarize etiopathogenetic knowledge of AIS as theories of pathogenesis including recent multiple concepts, and blood tests for AIS based on predictive biomarkers and genetic variants that signify disease risk. There is increasing evidence for the possibility of an underlying neurological disorder for AIS, research which holds promise. Like brain research, most AIS workers focus on their own corner and there is a need for greater integration of research effort. Epigenetics, a relatively recent field, evaluates factors concerned with gene expression in relation to environment, disease, normal development and aging, with a complex regulation across the genome during the first decade of life. Research on the role of environmental factors, epigenetics and chronic non-communicable diseases (NCDs) including adiposity, after a slow start, has exploded in the last decade. Not so for AIS research and the environment where, except for monozygotic twin studies, there are only sporadic reports to suggest that environmental factors are at work in etiology. Here, we examine epigenetic concepts as they may relate to human development, normal life history phases and AIS pathogenesis. Although AIS is not regarded as an NCD, like them, it is associated with whole organism metabolic phenomena, including lower body mass index, lower circulating leptin levels and other systemic disorders. Some epigenetic research applied to Silver-Russell syndrome and adiposity is examined, from which suggestions are made for consideration of AIS epigenetic research, cross-sectional and longitudinal. The word scoliogeny is suggested to include etiology, pathogenesis and pathomechanism.