Progress in the Understanding of the Genetic Etiology of Vertebral Segmentation Disorders in Humans

Abstract

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. This review explores (1) 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; (2) outcomes of molecular studies elucidating genetic contributions to congenital and sporadic vertebral malformation; and (3) complex interrelationships between genetic and environmental factors that contribute to the pathogenesis of isolated syndromic and nonsyndromic congenital vertebral malformation. Discussion includes exploration 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.

Fusionless procedures for the management of early-onset spine deformities in 2011: What do we know?

“…In contrast to children with adolescent idiopathic scoliosis, children with EOS represent a heterogeneous population. Children may have infantile idiopathic scoliosis with no other associated comorbidities or may have a primary thoracic insufficiency with severe pulmonary problems, as is present, for example, in Jarcho-Levin syndrome [24,25]. In order to understand the child with a crooked spine, we need a basis for differentiating the many different groups inherent in this population.…”

An N‐Ethyl‐N‐Nitrosourea (ENU) Mutagenized Mouse Model for Autosomal Dominant Nonsyndromic Kyphoscoliosis Due to Vertebral Fusion

“…The HVF mouse model resembles the failure of segmentation (block vertebrae) pattern (Figs. 1 and 2; Table 1) which has been reported in ∼3% of 251 patients with congenital scoliosis,44 and to have a prevalence of approximately 0.5 to 1 per 1000 individuals 9. Thus, identifying the genetic defect causing HVF may help to identify a component in the complex pathways regulating vertebral formation, which is likely to involve the expression of multiple genes.…”

“…Kyphosis, scoliosis, or kyphoscoliosis, can occur at any age, secondary to other underlying developmental, musculoskeletal, neuromuscular, or spinal disorders,5, 6, 7, 8, 9, 10 and may be part of complex disorders such as the CHARGE syndrome (coloboma of the eye, heart defects, atresia of the nasal choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness),9, 11 or occur as a nonsyndromic condition. Indeed, the most common forms of kyphosis and scoliosis in adolescents are nonsyndromic and include: Scheuermann disease3 a form of nonsyndromic kyphosis, which affects >8% of the population12; idiopathic scoliosis (IS), which affects approximately 2% to 3% individuals13, 14, 15, 16; and congenital nonsyndromic scoliosis, which is reported to have a prevalence of approximately 0.5 to 1 per 1000 individuals 9. Familial and twin studies have indicated a genetic basis for kyphosis17, 18, 19, 20 and scoliosis,21, 22, 23, 24, 25, 26, 27, 28 with likely genetic heterogeneity.…”

“…Familial and twin studies have indicated a genetic basis for kyphosis17, 18, 19, 20 and scoliosis,21, 22, 23, 24, 25, 26, 27, 28 with likely genetic heterogeneity. However, studies aimed at defining the genetic abnormalities causing these spinal disorders have been hampered by their phenotypic and genetic heterogeneity, variable modes of inheritance,8, 29 and gene‐environment interactions that may modify the phenotypic expression 9. To facilitate these studies, we investigated the progeny of mice treated with the chemical mutagen N ‐ethyl‐ N ‐nitrosourea (ENU),30 which is an alkylating agent that induces mutations in DNA at a frequency of 1 in every 1.5 megabases (Mb) 31.…”

Congenital Cervical Kyphosis in a Child Associated with Tetraparesis: Case Report

“…Each sclerotome cell divides in a cranial and a caudal part. The spinal nerves leave the neuronal tube and migrate to the sclerotome center where they innervate the myotomes [1]. …”