Multiple Hereditary Exostoses: Report of an EXT2 Gene Mutation in a Colombian Family

Abstract

Multiple hereditary exostoses (MHE) is a rare disease with autosomal dominant inheritance, caused by heterozygous germline mutations in the EXT1 or EXT2 genes. This disorder is characterized by the growth of prominences surrounded by cartilage in the growth plates and the long bones. Here, we report a family affected by MHE. In this family, a pathogenic variant c.544C > T (p. Arg182Ter) was identified in the EXT2 gene. This variant has been previously described in the literature, and here we are reporting the relationship with clinical findings. MHE is suspected according to the clinical manifestations; molecular research should be performed to establish the most frequent mutations. A support, diagnosis, and follow-up group should be created, and genetic counseling should be available for patients and families.

Keywords

hereditary multiple exostoses - EXT1 - EXT2 - osteochondroma - children

Authors' Contributions

All authors were involved in drafting and translation of the manuscript.

Publication History

Received: 05 November 2017

Accepted: 06 February 2018

Publication Date:
07 March 2018 (online)

• References

• 1 Pacifici M. Hereditary multiple exostoses: new insights into pathogenesis, clinical complications, and potential treatments. Curr Osteoporos Rep 2017; 15 (03) 142-152
• 2 Jones KB. Glycobiology and the growth plate: current concepts in multiple hereditary exostoses. J Pediatr Orthop 2011; 31 (05) 577-586
• 3 Dobson-Stone C, Cox RD, Lonie L. , et al. Comparison of fluorescent single-strand conformation polymorphism analysis and denaturing high-performance liquid chromatography for detection of EXT1 and EXT2 mutations in hereditary multiple exostoses. Eur J Hum Genet 2000; 8 (01) 24-32
• 4 Wu Y, Xing X, Xu S. , et al. Novel and recurrent mutations in the EXT1 and EXT2 genes in Chinese kindreds with multiple osteochondromas. J Orthop Res 2013; 31 (09) 1492-1499
• 5 Bovée JV. Multiple osteochondromas. Orphanet J Rare Dis 2008; 3 (03) 3
• 6 Phan AQ, Pacifici M, Esko JD. Advances in the pathogenesis and possible treatments for multiple hereditary exostoses from the 2016 international MHE conference. Connect Tissue Res 2018; 59 (01) 85-98
• 7 Stancheva-Ivanova MK, Wuyts W, van Hul E. , et al. Clinical and molecular studies of EXT1/EXT2 in Bulgaria. J Inherit Metab Dis 2011; 34 (04) 917-921
• 8 Jennes I, Pedrini E, Zuntini M. , et al. Multiple osteochondromas: mutation update and description of the multiple osteochondromas mutation database (MOdb). Hum Mutat 2009; 30 (12) 1620-1627
• 9 Pierz KA, Stieber JR, Kusumi K, Dormans JP. Hereditary multiple exostoses: one center's experience and review of etiology. Clin Orthop Relat Res 2002; (401) 49-59
• 10 Hill CE, Boyce L, van der Ploeg ID. Spontaneous resolution of a solitary osteochondroma of the distal femur: a case report and review of the literature. J Pediatr Orthop B 2014; 23 (01) 73-75
• 11 Jennes I, de Jong D, Mees K, Hogendoorn PC, Szuhai K, Wuyts W. Breakpoint characterization of large deletions in EXT1 or EXT2 in 10 multiple osteochondromas families. BMC Med Genet 2011; 12: 85
• 12 Sarrión P, Sangorrin A, Urreizti R. , et al. Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas. Sci Rep 2013; 3: 1346
• 13 Wuyts W, Schmale GA, Chansky HA. et al. Hereditary Multiple Osteochondromas; August 3, 2000 [Updated November 21, 2013]. In: Adam MP, Ardinger HH, Pagon RA. et al., eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993–2017. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1235/
• 14 Porter DE, Lonie L, Fraser M. , et al. Severity of disease and risk of malignant change in hereditary multiple exostoses. A genotype-phenotype study. J Bone Joint Surg Br 2004; 86 (07) 1041-1046