Molecular diagnosis of vertebral segmentation disorders in humans

Background: Vertebral malformations contribute substantially to the pathophysiology of kyphosis and scoliosis, common health problems associated with back and neck pain, disability, cosmetic disfigurement and functional distress. Objective: To provide an overview of the current understanding of vertebral malformations, at both the clinical level and the molecular level, and factors that contribute to their occurrence. Methods: The literature related to the following was reviewed: recent advances in the understanding of the molecular embryology underlying vertebral development and relevance to elucidation of etiologies of several known human vertebral malformation syndromes; outcomes of molecular studies elucidating genetic contributions to congenital and sporadic vertebral malformations; and complex interrelationships between genetic and environmental factors that contribute to the pathogenesis of isolated syndromic and non-syndromic congenital vertebral malformations. Results/conclusion: Expert opinions extend to discussion of the importance of establishing improved classification systems for vertebral malformation, future directions in molecular and genetic research approaches to vertebral malformation and translational value of research efforts to clinical management and genetic counseling of affected individuals and their families.