Hereditary Exostoses and Osteochondromas

Hereditary exostoses, often termed multiple osteochondromas, comprise a dominantly inherited skeletal disorder characterised by the development of two or more cartilage-capped bony outgrowths (osteochondromas) adjacent to the growth plates of long bones. These lesions typically emerge in childhood and cease expanding after skeletal maturity, but they can produce pain, deformity and impaired joint function. The condition arises primarily from heterozygous loss-of-function variants in the EXT1 or EXT2 genes, which encode Golgi-associated glycosyltransferases essential for heparan sulfate chain elongation. Disruption of heparan sulfate biosynthesis alters signalling within growth plates, leading to exostosis formation. Although most lesions are benign, up to 4 % may undergo malignant transformation into secondary peripheral chondrosarcoma. Clinical management ranges from periodic imaging and symptomatic excision of troublesome exostoses to corrective osteotomies for limb deformities. Advances in molecular diagnostics have improved genetic counselling, while emerging insights into growth-factor pathways offer potential avenues for targeted therapies.

Research from Nature Portfolio

A surgical series has refined correction of forearm deformity in children with hereditary multiple exostosis presenting Masada type 2 features. After excision of distal ulnar and proximal radial osteochondromas, a modified Ilizarov external fixator enabled gradual ulnar lengthening and reliable radial head relocation, yielding significant improvements in forearm alignment and elbow function over a three-year follow-up. Separately, a foundational mutational analysis in a Mediterranean cohort identified novel and recurrent loss-of-function variants in EXT1 and EXT2, demonstrating that targeted gene sequencing captures over 90 % of pathogenic alleles. This work underpins current diagnostic pipelines and provides a reference for genotype–phenotype correlations in diverse populations.

Hereditary Exostoses and Osteochondromas publication trend

The graph below shows the total number of articles in hereditary exostoses and osteochondromas across all publications each year (not limited to Nature Index journals).

Technical terms

Exostosis: A benign bony projection capped by cartilage arising near growth plates.

Osteochondroma: The most common benign bone tumour, formed by an exostosis with a cartilage cap.

EXT1/EXT2 genes: Tumour-suppressor genes encoding glycosyltransferases required for heparan sulfate polymerisation.

Ilizarov external fixation: A circular ring-frame apparatus facilitating controlled distraction osteogenesis.

Genu valgum: A deformity in which the knees angle inward and touch one another when the legs are straightened.

References

1. Multiple osteochondromas. Orphanet Journal of Rare Diseases (2008).
2. Hereditary Multiple Exostoses—A Review of the Molecular Background, Diagnostics, and Potential Therapeutic Strategies. Frontiers in Genetics (2021).
3. The Putative Tumor Suppressors EXT1 and EXT2 Are Glycosyltransferases Required for the Biosynthesis of Heparan Sulfate*. Journal of Biological Chemistry (1998).
4. Modified ulnar lengthening for correction of the Masada type 2 forearm deformity in hereditary multiple exostosis. Scientific Reports (2023).
5. Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas. Scientific Reports (2013).
6. The Missing Piece of the Puzzle: Unveiling the Role of PTPN11 Gene in Multiple Osteochondromas in a Large Cohort Study. Human Mutation (2024).
7. Tibia Valga Correction by Extraperiosteal Fibular Release in Multiple Exostosis Disease. Biomedicines (2023).