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Etiology

Abstract: Congenital scoliosis is an abnormal lateral curvature of the spine, resulting from disruption of normal vertebral development. Although there are many types of defects observed in congenital scoliosis, all result from abnormal formation and segmentation of the vertebral precursors, called somites. Developmental studies in animal models have identified many genes regulating somite formation and segmentation. The interaction of environmental factors and these genes, is thought to be disrupted resulting in deformities such as congenital scoliosis. A basic science research program and a large, multi-center clinical genetic study of congenital scoliosis and kyphosis have been established at our institution. Studying the developmental mechanisms in vertebral patterning may aid in the identification of some protective factors for normal spinal development, towards the prevention of disfiguring congenital scoliosis.

Introduction
Congenital scoliosis is a lateral curvature of the spine that is due to the presence of vertebral anomalies that cause an imbalance in the longitudinal growth of the spine. While congenital scoliosis is often recognized at birth, more subtle spinal defects can remain undetected. A key feature of congenital scoliosis is the presence of one or more abnormally formed vertebrae. When these anomalies are identified, the curve should be classified as congenital, even if the deformity is not apparent until adolescence.

The vertebrae of the spine are formed during development by segmentation of the precursor spine tissue, in a process called somitogenesis. In this process, segments of tissue called somites are formed in pairs surrounding what will eventually become the spinal cord. When somitogenesis is disrupted even slightly, as has been done in animal models, congenital vertebral defects identical to those in congenital scoliosis have resulted. Developmental studies in animal models have identified many genes regulating somite formation and segmentation. Recently, genes in the "notch" family have been shown to regulate development of vertebral precursors in the mouse and defects in human notch genes have been associated with congenital vertebral defects.

Congenital vertebral anomalies have been produced in newborn animals experimentally by transient hypoxia and transient exposure to toxic elements during fetal period. In these studies, many gross vertebral and associated skeletal defects have been induced, including hemivertebrae, vertebral fusions, fragmented vertebral bodies, bifid ribs or junctions of two or more ribs. The nature and extent of skeletal malformations induced have been dependent upon the precise stage of somite differentiation at the time when maternal stress has been induced.

Currently, researchers hypothesize that the environmental factors affect the delivery of the genetic instructions during development, so it is the close interaction of genes and environment that produce the normal spine. This interaction is thought to be disrupted in deformities such as congenital scoliosis. We have initiated a large, multi-center clinical genetic study of congenital vertebral defects at our institution. Work centers on identifying genetic factors underlying these vertebral anomalies and using animal models to examine the developmental origins of these defects. Studying the developmental mechanisms in vertebral patterning will aid in the identification of protective factors for normal spinal development, toward the prevention of disfiguring congenital scoliosis.

Classification
The congenital vertebral anomalies are classified based on failure of formation, failure of segmentation and a combination of the two (mixed) (Fig. 1). The most common type of failure of formation anomaly is a hemivertebra. This is where a portion of the vertebra is missing resulting in a small, triangular shaped "half vertebra" or hemivertebra. Hemivertebrae can be subclassified based on their relationship to the adjacent spine (segmented, semisegmented, nonsegmented). When several vertebral segments fail to separate bilaterally, a block vertebra results producing fused vertebral bones. Unilateral unsegmented vertebral bars are caused by the failure of segmentation only on the left or right side of the spine.

Hermivertebrae and Unsegmented Vertebrae
Hermivertebrae and Unsegmented Vertebrae

Fig. 1. Diagrammatic representation of classification system of congenital scoliosis. (A) Failures of formation; various types of hemivertebrae (semisegmented, fully segmented, wedge vertebra). (B) Failures of segmentation; block vertebra, unsegmented bar.

In the involved area of the spine there is absent or abnormal growth potential due to an area of missing bone (formation defect) or missing growth plates (segmentation defect). This results in an area of absent growth potential in the vertebral ring, and the growth in the remainder of the vertebral ring disrupts the normal alignment of the spine, producing different types of deformities. Failures of formation or segmentation may occur on either the right or left side of the body resulting in "pure" scoliosis (Fig. 2), or in the anterior or posterior elements resulting in "pure" kyphosis or lordosis, respectively. Combined deformities are most common, producing scoliosis and sagittal plane deformity.

Congenital Scoliosis X-Ray
Congenital Scoliosis X-Ray

Fig. 2. Plain radiographs of a pediatric patient with congenital scoliosis. (A) Posterior--anterior and (B) lateral views of the spine, with multiple congenital vertebral anomalies including hemivertebrae at thoracic and lumbar spine and block vertebrae at lumbar spine.