Genetic aspects of congenital and idiopathic scoliosis

Abstract

Congenital and idiopathic scoliosis represent disabling conditions of the spine. While congenital scoliosis (CS) is caused by morphogenic abnormalities in vertebral development, the cause(s) for idiopathic scoliosis is (are) likely to be varied, representing alterations in skeletal growth, neuromuscular imbalances, disturbances involving communication between the brain and spine, and others. Both conditions are characterized by phenotypic and genetic heterogeneities, which contribute to the difficulties in understanding their genetic basis that investigators face. Despite the differences between these two conditions there is observational and experimental evidence supporting common genetic mechanisms. This paper focuses on the clinical features of both CS and IS and highlights genetic and environmental factors which contribute to their occurrence. It is anticipated that emerging genetic technologies and improvements in phenotypic stratification of both conditions will facilitate improved understanding of the genetic basis for these conditions and enable targeted prevention and treatment strategies.

Figure 1

Diagram of spine illustrating defects of formation (wedge and hemivertebrae) and segmentation (vertebral bar and block vertebrae). Reprinted with permission from McMaster [6].

Figure 2

3D reconstruction illustrating congenital scoliosis. Left T4 hemivertebrae displayed. Courtesy of Dr. Kenneth Noonan.

Figure 3

Algorithm for International Consortium for Vertebral Anomalies and Scoliosis (ICVAS) classification of congenital vertebral malformation. Reproduced with permission Expert opinion in [7]. Reproduced from Expert Opinion in Expert Opin. Med. Diagn. (2008) 2(10):1107-1121 with permission of Informa UK Ltd.

Figure 4

Illustration of somite formation from the presomitic mesoderm (PSM) in the chick embryo. Paired somites are formed every 90 minutes in a periodic fashion every 90 minutes shown in (a). (b).A molecular clocked linked to segmentation by dynamic and periodic expression of the cyclic genes in the PSM. Top: Lunatic Fringe mRNA expression appears as a wave sweeping across the whole PSM once during each somite formation as illustrated by in situ hybridization in this 17-somite-old chick embryo. During each somite formations, PSM cells illustrated by the dot undergo a phase of upregulation of the cycling genes followed by a phase of down regulation of these genes. Bottom: As shown in this schematic representation of the progression of somitogenesis in the embryo, the cycles of expression of the cyclic genes will last while the cells remain in the PSM, which corresponds approximately to the time to form 12 somites in the chick embryo. These PSM cells undergo 12 oscillations of the expression of the cycling genes. Reproduced with permission Expert Opinion in [9]. Reproduced from Expert Opinion in Expert Opin. Med. Diagn. (2008) 2(10):1107-1121 with permission of Informa UK Ltd.

Figure 5

Radiographic features of spondylocostal dystostosis including contiguous vertebral malformations with asymmetric rib malformations. Photograph courtesy of Peter D. Turnpenny M.D., Royal Devon and Exeter Hospital.

Figure 6

Radiograph features of spondylothoracic dysostosis demonstrating contiguous vertebral malformations with symmetric posterior rib fusion. Reproduced with permission Expert Opinion in [9].