Formation Errors of the Vertebral Column

Abstract

Congenital vertebral malformations result when the normal induction and formation of the axial skeleton is disrupted during embryonic development1. During early embryonic development, somites, which are transient precursors of the axial skeleton, are formed in a process called somitogenesis2 (Fig. 1). Disruptions in somitogenesis cause vertebral malformations3, including the formation of uneven segments (hemivertebrae and wedge vertebrae), fused segments (block vertebrae), and vertebrae with failure of midline fusion (butterfly vertebrae). Congenital vertebral defects that result from disruption of the induction and formation of the axial skeleton include Klippel-Feil syndrome, spondylocostal dysostosis, Jarcho-Levin syndrome, congenital scoliosis and kyphosis, and a wide range of syndromes and associations (e.g., oculoauriculovertebral dysplasia [Goldenhar syndrome] and the VATER [vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, and radial and renal anomalies] and VACTERL [vertebral, anal, cardiac, tracheoesophageal, renal, and limb abnormalities] associations)4-10. While there is frequently overlap in diagnostic classification for these disorders, differences in severity and localization of defects can aid in defining general categories. Vertebral malsegmentation can be observed globally (as in spondylocostal dysostosis or Jarcho-Levin syndrome) or regionally (as in the cervical vertebral fusions of Klippel-Feil syndrome) or in one or two vertebrae (as in Alagille syndrome or some forms of congenital scoliosis). Disruption of genes involved in axial skeletal development, environmental insults during gestation, or a combination of these factors can lead to vertebral defects. The availability of the human genome sequence is aiding in the identification of genetic causes of vertebral malformations. As discussed below, the developmental mechanisms regulating somitogenesis can lead to segmental defects. Fig. 1 Diagram illustrating the normal formation of somites (the embryonic precursors to the vertebrae, ribs, and axial musculature) and the consequences of defects in early development. nt = neural tube. psm = presomitic mesoderm. The severe …