Severity of disease and risk of malignant change in hereditary multiple exostoses. A genotype-phenotype study
| Autor: | Daniel E Porter, M. Fraser, Lorne Lonie, Carol Dobson-Stone, Anthony P. Monaco, Ahrw Simpson, J. R. Porter |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Pediatrics Adolescent Genotype Hereditary multiple exostoses Chondrosarcoma Bone Neoplasms Disease N-Acetylglucosaminyltransferases Severity of Illness Index Age Distribution Severity of illness medicine Humans Genetic Predisposition to Disease Orthopedics and Sports Medicine Prospective Studies Risk factor Child Prospective cohort study Aged business.industry Middle Aged medicine.disease Penetrance Osteochondrodysplasia Phenotype Mutation Female Surgery business Precancerous Conditions Exostoses Multiple Hereditary |
| Zdroj: | Porter, D E, Lonie, L, Fraser, M, Dobson-Stone, C, Porter, J R, Monaco, A P & Simpson, H 2004, ' Severity of disease and risk of malignant change in hereditary multiple exostoses. A genotype-phenotype study ', Journal of Bone and Joint Surgery, British Volume, vol. 86, no. 7, pp. 1041-6 . https://doi.org/10.1302/0301-620X.86B7.14815 |
| DOI: | 10.1302/0301-620x.86b7.14815 |
| Popis: | We performed a prospective genotype-phenotype study using molecular screening and clinical assessment to compare the severity of disease and the risk of sarcoma in 172 individuals (78 families) with hereditary multiple exostoses. We calculated the severity of disease including stature, number of exostoses, number of surgical procedures that were necessary, deformity and functional parameters and used molecular techniques to identify the genetic mutations in affected individuals. Each arm of the genotype-phenotype study was blind to the outcome of the other. Mutations EXT1 and EXT2 were almost equally common, and were identified in 83% of individuals. Non-parametric statistical tests were used. There was a wide variation in the severity of disease. Children under ten years of age had fewer exostoses, consistent with the known age-related penetrance of this condition. The severity of the disease did not differ significantly with gender and was very variable within any given family. The sites of mutation affected the severity of disease with patients with EXT1 mutations having a significantly worse condition than those with EXT2 mutations in three of five parameters of severity (stature, deformity and functional parameters). A single sarcoma developed in an EXT2 mutation carrier, compared with seven in EXT1 mutation carriers. There was no evidence that sarcomas arose more commonly in families in whom the disease was more severe. The sarcoma risk in EXT1 carriers is similar to the risk of breast cancer in an older population subjected to breast-screening, suggesting that a role for regular screening in patients with hereditary multiple exostoses is justifiable. |
| Databáze: | OpenAIRE |
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