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.

ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease

“…3,39 To determine whether segmentation is disrupted in MZ ptk7 mutant embryos, we performed in situ hybridization of her7 and dlc (direct reporters of the Notch segmentation mechanism and nascent somite differentiation) 40 within the presomitic mesoderm of 18-20 somite-staged MZ ptk7 mutant embryos, looking for possible irregularities in gene expression. The PSM domain was broader and expanded relative to total body length in MZ ptk7 mutants, consistent with a role for Ptk7 in tailbud patterning and morphogenesis.…”

“…Consequently, the MZ ptk7 mutant phenotype may be more reminiscent of non-syndromic mild or moderate cases of CS where individuals display relatively few CVMs at irregular locations along the length of the spine. 3 …”

“…1,2 Scoliosis caused by congenital vertebral malformation (CVM) is referred to as congenital scoliosis (CS) and affects 0.13-0.5/1,000 live human births. 1,3 CVMs like hemivertebrae, wedge-shaped vertebrae, vertebral fusions and/or vertebral bar can exist throughout the spine and often impose severe deformity on affected individuals. In mammals, vertebral bodies are derived from somites – periodic segments of paraxial mesoderm that form in pairs along the cranial to caudal axis in response to an internal “segmentation clock”.…”

IDENTIFICATION OF SNPs IGF-1 GENE IN VERTICAL MANDIBULAR ASYMMETRY PATIENTS WITH IDIOPATHIC SCOLIOSIS SYMPTOM

“…The assessment of growth potential is essential because of different maturational statuses as well as the type of maturation and mandibular growth influence the diagnosis and prognosis of orthodontic treatment. Unraveling the genetic contributions for both conditions can help to provide improved genetic counseling, prevention, and treatment strategies for this phenotype [6]. Some studies reported that the benefits of early detection of IGF-1 gene might be as one of the principal mediators in promoting muscular and skeletal growth to optimize the timing of orthodontic treatment, indeed in orthopaedic treatment [25][26][27].…”

“…Mandibular asymmetry is the asymmetric growth of mandible that due to complicated postnatal growth abnormality of the mandibular condyle [3][4][5]. In understanding the genetic aspects of congenital and idiopathic scoliosis, Giampietro suggested that craniofacial asymmetry as one of the major clinical features of oculoauriculo-vertebral spectrum [6]. However, the abnormalities in the skeletal, nerve, endocrine systems, and connective tissue for both asymmetries in the bilateral joint of temporomandibular and spinal still unclear whether these are primary or secondary.…”