Introduction and Aims: Hereditary Multiple Exostosis is an autosomal dominant condition in which multiple benign cartilage-capped tumors grow in relation to the growth plates of long and flat bones. The purpose of this study was to determine the relationship between the genotype and phenotype in HME.

Method: Ten families were identified with HME. Genotyping was completed by linkage analysis of all families and the EXT 1 or 2 gene was sequenced based on these results. Mutation identification and confirmation was performed. Phenotyping consisting of clinical and radiographic examinations generated 89 features for each subject.

Results: Eight of 10 mutations were identified, confirmed and segregation verified. Six of the mutations were unique and two previously had been reported in the literature. Three mutations were in EXT 1 and five in EXT 2. Two were missense, three nonsense, two splice site and one frameshift. EXT 1 patients were found to have more exostoses, with a higher percentage of flat and pelvic bone involvement. EXT 1 patients had more malalignment and were shorter. Males also had a more severe phenotype and modulated the severity of EXT 1 expression. No other genotypic factors were found to influence phenotype.

Conclusion: An established genotype phenotype correlation will aid in patient management in terms of surveillance, determining prognosis and management. It was found that a genotype phenotype correlation exists where EXT 1 is linked to a more severe phenotype.