Dataset Information

Congenital and idiopathic scoliosis: clinical and genetic aspects.

ABSTRACT: OBJECTIVE:Genetic and environmental factors influencing spinal development in lower vertebrates are likely to play a role in the abnormalities associated with human congenital scoliosis (CS) and idiopathic scoliosis (IS). An overview of the molecular embryology of spinal development and the clinical and genetic aspects of CS and IS are presented. Utilizing synteny analysis of the mouse and human genetic databases, likely candidate genes for human CS and IS were identified. DESIGN:Review and synteny analysis. METHODS:A search of the Mouse Genome Database was performed for "genes," "markers" and "phenotypes" in the categories Neurological and neuromuscular, Skeleton, and Tail and other appendages. The Online Mendelian Inheritance in Man was used to determine whether each mouse locus had a known human homologue. If so, the human homologue was assigned candidate gene status. Linkage maps of the chromosomes carrying loci with possibly relevant phenotypes, but without known human homologues, were examined and regions of documented synteny between the mouse and human genomes were identified. RESULTS:Searching the Mouse Genome Database by phenotypic category yielded 100 mutants of which 66 had been mapped. The descriptions of each of these 66 loci were retrieved to determine which among these included phenotypes of scoliosis, kinky or bent tails, other vertebral abnormalities, or disturbances of axial skeletal development. Forty-five loci of interest remained, and for 27 of these the comparative linkage maps of mouse and human were used to identify human syntenic regions to which plausible candidate genes had been mapped. CONCLUSION:Synteny analysis of mouse candidate genes for CS and IS holds promise due to the close evolutionary relationship between mice and human beings. With the identification of additional genes in animal model systems that contribute to different stages of spine development, the list of candidate genes for CS and IS will continue to grow.

SUBMITTER: Giampietro PF

PROVIDER: S-EPMC1069035 | biostudies-literature | 2003 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Congenital and idiopathic scoliosis: clinical and genetic aspects.

Giampietro Philip F PF Blank Robert D RD Raggio Cathleen L CL Merchant Sajid S Jacobsen F Stig FS Faciszewski Thomas T Shukla Sanjay K SK Greenlee Anne R AR Reynolds Cory C Schowalter David B DB

Clinical medicine & research 20030401 2

<h4>Objective</h4>Genetic and environmental factors influencing spinal development in lower vertebrates are likely to play a role in the abnormalities associated with human congenital scoliosis (CS) and idiopathic scoliosis (IS). An overview of the molecular embryology of spinal development and the clinical and genetic aspects of CS and IS are presented. Utilizing synteny analysis of the mouse and human genetic databases, likely candidate genes for human CS and IS were identified.<h4>Design</h4> ...[more]

PMID: 15931299

Similar Datasets

Project description:BackgroundThere is an acknowledged discrepancy between radiographic and cosmetic parameters for patients with adolescent idiopathic scoliosis (AIS). However, no study has specifically evaluated cosmesis in patients with congenital scoliosis (CS). Therefore, the purpose of this study was to identify the cosmetic differences between patients with CS and case-matched patients with AIS and to investigate the correlation between radiological measurements and clinical cosmetic assessment indices.MethodsA total of 37 adolescents with CS and 37 sex-, age-, and curve magnitude-matched patients with AIS were included. Cobb angle, shoulder height difference (SHD), coronal balance (CB), T1 tilt, first rib angle (FRA), clavicle angle (CA), clavicle-rib cage intersection (CRCI), and apical vertebra translation (AVT) were measured in the full X-ray of the spine. Shoulder area index 1 (SAI1), shoulder area index 2 (SAI2), shoulder angle (SA), axilla angle (AA), thoracolumbar area index (TLAI), and right and left waist angle difference (RLWAD) were measured on the clinical images from a posterior view. Hump index (HI) was measured in the forward bending photography. All patients completed the Scoliosis Research Society-22 (SRS-22) questionnaire.ResultsNo significant difference was noted in the radiographic parameters between the AIS and CS groups (P>0.05). However, patients with CS exhibited significantly lower SAI1 (0.91 vs. 0.98; P=0.002) and SAI2 (0.85 vs. 0.95; P=0.001) than did the patients with AIS. The SRS-22 scores for self-image and mental health in patients with CS were significantly lower than those in patients with AIS (P<0.05). The correlation coefficients with statistical significance between radiographic and cosmetic measurements in patients with CS and those with AIS ranged from -0.493 to 0.534 and from -0.653 to 0.717, respectively. None of the correlation coefficients exceeded 0.8, indicating that the current radiological indices only exhibited a limited level of consistency with patients' cosmesis.ConclusionsAs compared with age-, gender-, and curve pattern-matched patients with AIS, patients with CS exhibited worse cosmesis and had clinically significantly lower SRS-22 scores despite having relatively small clinical differences. Although the radiographic parameters may not always align with clinical presentation, this discrepancy could be observed in both patients with CS and those with AIS.

Project description:BACKGROUND:We previously reported a novel clinically distinguishable subtype of congenital scoliosis (CS), namely, TBX6-associated congenital scoliosis (TACS). We further developed the TBX6-associated CS risk score (TACScore), a multivariate phenotype-based model to predict TACS according to the patient's clinical manifestations. In this study, we aimed to evaluate whether using the TACScore as a screening method prior to performing whole-exome sequencing (WES) is more cost-effective than using WES as the first-line genetic test for CS. METHODS:We retrospectively collected the molecular data of 416 CS patients in the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study. A decision tree was constructed to estimate the cost and the diagnostic time required for the two alternative strategies (TACScore versus WES). Bootstrapping simulations and sensitivity analyses were performed to examine the distributions and robustness of the estimates. The economic evaluation considered both the health care payer and the personal budget perspectives. RESULTS:From the health care payer perspective, the strategy of using the TACScore as the primary screening method resulted in an average cost of $1074.2 (95%CI: $1044.8 to $1103.5) and an average diagnostic duration of 38.7d (95%CI: 37.8d to 39.6d) to obtain a molecular diagnosis for each patient. In contrast, the corresponding values were $1169.6 (95%CI: $1166.9 to $1172.2) and 41.4d (95%CI: 41.1d to 41.7d) taking WES as the first-line test (P?<?0.001). From the personal budget perspective, patients who were predicted to be positive by the TACScore received a result with an average cost of $715.1 (95%CI: $594.5 to $835.7) and an average diagnostic duration of 30.4d (95%CI: 26.3d to 34.6d). Comparatively, the strategy of WES as the first-line test was estimated to have significantly longer diagnostic time with an average of 44.0d (95%CI: 43.2d to 44.9d), and more expensive with an average of $1193.4 (95%CI: $1185.5 to $1201.3) (P?<?0.001). In 100% of the bootstrapping simulations, the TACScore strategy was significantly less costly and more time-saving than WES. The sensitivity analyses revealed that the TACScore strategy remained cost-effective even when the cost per WES decreased to $8.8. CONCLUSIONS:This retrospective study provides clinicians with economic evidence to integrate the TACScore into clinical practice. The TACScore can be considered a cost-effective tool when it serves as a screening test prior to performing WES.

Dataset Information

Congenital and idiopathic scoliosis: clinical and genetic aspects.

Publications

Congenital and idiopathic scoliosis: clinical and genetic aspects.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets