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Current Osteoporosis Reports
Published in: Current Osteoporosis Reports 3/2017

01-06-2017 | Rare Bone Diseases (C Langman and E Shore, Section Editors)

Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments

Author: Maurizio Pacifici

Published in: Current Osteoporosis Reports | Issue 3/2017

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Abstract

Purpose of Review

Hereditary multiple exostoses (HME) is a complex musculoskeletal pediatric disorder characterized by osteochondromas that form next to the growth plates of many skeletal elements, including long bones, ribs, and vertebrae. Due to its intricacies and unresolved issues, HME continues to pose major challenges to both clinicians and biomedical researchers. The purpose of this review is to describe and analyze recent advances in this field and point to possible targets and strategies for future biologically based therapeutic intervention.

Recent Findings

Most HME cases are linked to loss-of-function mutations in EXT1 or EXT2 that encode glycosyltransferases responsible for heparan sulfate (HS) synthesis, leading to HS deficiency. Recent genomic inquiries have extended those findings but have yet to provide a definitive genotype-phenotype correlation. Clinical studies emphasize that in addition to the well-known skeletal problems caused by osteochondromas, HME patients can experience, and suffer from, other symptoms and health complications such as chronic pain and nerve impingement. Laboratory work has produced novel insights into alterations in cellular and molecular mechanisms instigated by HS deficiency and subtending onset and growth of osteochondroma and how such changes could be targeted toward therapeutic ends.

Summary

HME is a rare and orphan disease and, as such, is being studied only by a handful of clinical and basic investigators. Despite this limitation, significant advances have been made in the last few years, and the future bodes well for deciphering more thoroughly its pathogenesis and, in turn, identifying the most effective treatment for osteochondroma prevention.
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Metadata
Title
Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments
Author
Maurizio Pacifici
Publication date
01-06-2017
Publisher
Springer US
Published in
Current Osteoporosis Reports / Issue 3/2017
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-017-0355-2

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