Prague Med. Rep. 2017, 118, 87-94

https://doi.org/10.14712/23362936.2017.8

Hereditary Multiple Exostoses: Clinical, Molecular and Radiologic Survey in 9 Families

Karel Medek1, Jiří Zeman1, Tomáš Honzík1, Hana Hansíková1, Štěpánka Švecová1, Kamila Beránková1, Vendula Kučerová Vidrová1, Miloslav Kuklík2, Jiří Chomiak3, Markéta Tesařová1

1Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
2Genetic Department, Prague, Czech Republic
3Department of Orthopaedics, First Faculty of Medicine, Charles University and Na Bulovce Hospital, Prague, Czech Republic

Received March 22, 2017
Accepted August 28, 2017

Hereditary multiple exostoses (HME) represents a heterogeneous group of diseases often associated with progressive skeletal deformities. Most frequently, mutations in EXT1 and EXT2 genes with autosomal dominant inheritance are responsible for HME. In our group of 9 families with HME we evaluated the clinical course of the disease and analysed molecular background using Sanger sequencing and MLPA in EXT1 and EXT2 genes. The mean age in our group of patients, when the first exostosis was recognised was 4.5 years (range 2–10 years) and the number of exostoses per one patient documented on X-ray ranged from 2 to 54. Most of the exostoses developed before the growth was completed and they were dominantly localised in the distal femurs, proximal tibia, proximal humerus and distal radius. In all patients, at least one to 8 surgeries were necessary due to complaints and local complications, but neither patient developed malignant transformation. In half of the patients, the disease resulted in short stature. DNA analyses were positive in 7 families. In five probands, different EXT1 gene mutations resulting in premature stop-codon (p.Gly124Argfs*65, p.Leu191*, p.Trp364Lysfs*11, p.Val371Glyfs*10, p.Leu490Profs*31) were found. In two probands, nonsense mutations were found in EXT2 gene (p.Val187Profs*115, p.Cys319fs*46). Five mutations have been novel and two mutations have occurred de novo in probands. Although the risk for malignant transformation is usually low, especially in patients with low number of exostoses, early diagnostics and longitudinal follow up of patients is of a big importance, because early surgery can prevent progression of secondary bone deformities.

Funding

This study was supported by grant AZV 16-31932A from the Ministry of Health of the Czech Republic and by institutional research support PROGRES Q32/LF2 from the Charles University and RVO-VFN64165/2012 from the Ministry of Health of the Czech Republic.

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