TY - JOUR
T1 - Genotype-phenotype correlation study in 529 patients with multiple hereditary exostoses
T2 - Identification of "protective" and "risk" factors
AU - Pedrini, Elena
AU - Jennes, Ivy
AU - Tremosini, Morena
AU - Milanesi, Annamaria
AU - Mordenti, Marina
AU - Parra, Alessandro
AU - Sgariglia, Federica
AU - Zuntini, Monia
AU - Campanacci, Laura
AU - Fabbri, Nicola
AU - Pignotti, Elettra
AU - Wuyts, Wim
AU - Sangiorgi, Luca
PY - 2011/12/21
Y1 - 2011/12/21
N2 - Background: Multiple hereditary exostoses is an autosomal dominant skeletal disorder characterized by wide variation in clinical phenotype. The aim of this study was to evaluate whether the severity of the disease is linked with a specific genetic background. Methods: Five hundred and twenty-nine patients with multiple hereditary exostoses from two different European referral centers participated in the study. According to a new clinical classification based on the presence or absence of deformities and functional limitations, the phenotype of the patients was assessed asmild (the absence of both aspects), intermediate, or severe (the concurrent presence of both aspects). An identicalmolecular screening protocol with denaturing high-performance liquid chromatography and multiplex ligation-dependent probe amplification was performed in both institutions. Results: In our cohort of patients, variables such as female sex (odds ratio = 1.840; 95% confidence interval, 1.223 to 2.766), fewer than five skeletal sites with exostoses (odds ratio = 7.588; 95% confidence interval, 3.479 to 16.553), EXT2 mutations (odds ratio = 2.652; 95% confidence interval, 1.665 to 4.223), and absence of EXT1/2 mutations (odds ratio = 1.975; 95% confidence interval, 1.051 to 3.713) described patients with a mild phenotype; in contrast, a severe phenotype was associated with male sex (odds ratio = 2.431; 95% confidence interval, 1.544 to 3.826), EXT1 mutations (odds ratio = 6.817; 95% confidence interval, 1.003 to 46.348), and more than twenty affected skeletal sites (odds ratio = 2.413; 95% confidence interval, 1.144 to 5.091). Malignant transformation was observed in 5% of patients, and no evidence of association between chondrosarcoma onset and EXT mutation, sex, severity of disease, or number of lesions was detected. Conclusions: The identified "protective" and "risk" factors, as well as the proposed classification system, represent helpful tools for clinical management and follow-up of patients with multiple hereditary exostoses; moreover, homogeneous cohorts of patients, useful for studies on the pathogenesis of multiple hereditary exostoses, have been identified. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.
AB - Background: Multiple hereditary exostoses is an autosomal dominant skeletal disorder characterized by wide variation in clinical phenotype. The aim of this study was to evaluate whether the severity of the disease is linked with a specific genetic background. Methods: Five hundred and twenty-nine patients with multiple hereditary exostoses from two different European referral centers participated in the study. According to a new clinical classification based on the presence or absence of deformities and functional limitations, the phenotype of the patients was assessed asmild (the absence of both aspects), intermediate, or severe (the concurrent presence of both aspects). An identicalmolecular screening protocol with denaturing high-performance liquid chromatography and multiplex ligation-dependent probe amplification was performed in both institutions. Results: In our cohort of patients, variables such as female sex (odds ratio = 1.840; 95% confidence interval, 1.223 to 2.766), fewer than five skeletal sites with exostoses (odds ratio = 7.588; 95% confidence interval, 3.479 to 16.553), EXT2 mutations (odds ratio = 2.652; 95% confidence interval, 1.665 to 4.223), and absence of EXT1/2 mutations (odds ratio = 1.975; 95% confidence interval, 1.051 to 3.713) described patients with a mild phenotype; in contrast, a severe phenotype was associated with male sex (odds ratio = 2.431; 95% confidence interval, 1.544 to 3.826), EXT1 mutations (odds ratio = 6.817; 95% confidence interval, 1.003 to 46.348), and more than twenty affected skeletal sites (odds ratio = 2.413; 95% confidence interval, 1.144 to 5.091). Malignant transformation was observed in 5% of patients, and no evidence of association between chondrosarcoma onset and EXT mutation, sex, severity of disease, or number of lesions was detected. Conclusions: The identified "protective" and "risk" factors, as well as the proposed classification system, represent helpful tools for clinical management and follow-up of patients with multiple hereditary exostoses; moreover, homogeneous cohorts of patients, useful for studies on the pathogenesis of multiple hereditary exostoses, have been identified. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.
UR - http://www.scopus.com/inward/record.url?scp=84855377136&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84855377136&partnerID=8YFLogxK
U2 - 10.2106/JBJS.J.00949
DO - 10.2106/JBJS.J.00949
M3 - Article
C2 - 22258776
AN - SCOPUS:84855377136
VL - 93
SP - 2294
EP - 2302
JO - Journal of Bone and Joint Surgery - Series A
JF - Journal of Bone and Joint Surgery - Series A
SN - 0021-9355
IS - 24
ER -