Abstract
Introduction
Studies of the vestibular system in patients with idiopathic scoliosis (IS) have shown abnormalities in the semicircular canals (SCC) and the basicranium. Rousie (2008) revealed a statistically increased incidence of structural anomalies in the SCCs with three-dimensional computer generated modelling. Some of these findings were replicated in a small population by Cheng (2010). The primary goals of this investigation are verification of SCC abnormalities of patients with IS versus controls with use of three-dimensional modelling with subsequent development of a unique phenotypical classification. Our long-term goal is to provide new direction for hypothesis directed identification and characterisation of genes causally related to IS.
Methods
20 patients with IS and 20 controls matched for age and sex will be identified through the clinic with approval from the institutional review board. Power analyses were done to detect the difference in distributions as the proportion of fisher tests with p values less than 0·05. A sample size of 20 per group gives 86–99% power to realise results under conservative assumptions. IS patients and controls undergo vestibular system examination via T2 MRI imaging. Extracted data are evaluated by a team including Dr Rousie, ENT, radiology, and orthopaedic surgery. DNA is extracted with Gentra Puregene kits from Qiagen (Valencia, CA, USA). Developmental genes related to SCC and axial somatogenesis are being identified through a bioinformatics approach, targeting known IS genomic loci. Custom single-nucleotide polymorphism panels, statistical linkage, and association will identify genes of significance for sequencing.
Results
To date, 11 patients with IS and four controls have been recruited. Preliminary data are indicative of a significant percentage of abnormalities within the SCC system in children with IS. Analyses of preliminary findings continue according to the protocol.
Conclusions
Research into genetic factors predicting IS progression and/or magnitudes of curvature have been inconclusive. Whether these abnormalities are primary or secondary to a larger systemic issue is speculative; however, they demonstrate a potential new phenotypical classification. Our initial findings show evidence of SCC abnormalities in patients with IS in a well defined patient population compared with healthy controls. Ultimately, our goal for this project is to pursue investigations of genes, pseudogenes, and conserved sequences shown to be related to vestibular structural formation during embryogenesis and development. The identification of a subset of individuals with IS and vestibular abnormalities will allow for the study of genes involved concomitantly in the embryological development of both systems, thus providing insight into the inter-relationship of these deformities.
