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

Area of Science:

• Genetics
• Orthopedics
• Molecular Biology

Background:

• Hereditary multiple exostoses (HME) is a group of genetic disorders characterized by progressive skeletal deformities.
• Mutations in EXT1 and EXT2 genes, inherited in an autosomal dominant pattern, are the most common cause of HME.

Purpose of the Study:

• To evaluate the clinical course of HME in families.
• To analyze the molecular basis of HME by sequencing EXT1 and EXT2 genes.
• To correlate genotype with clinical presentation and outcomes.

Main Methods:

• Clinical evaluation of 9 HME families.
• Molecular analysis using Sanger sequencing and MLPA for EXT1 and EXT2 genes.
• Identification and characterization of gene mutations.

Main Results:

• The mean age of first exostosis recognition was 4.5 years, with an average of 2-54 exostoses per patient.
• Exostoses predominantly affected distal femurs, proximal tibias, proximal humeri, and distal radii.
• Genetic analysis confirmed mutations in EXT1 or EXT2 in 7 out of 9 families, including novel mutations and de novo cases.
• Half of the patients experienced short stature, and all required surgery for complications; no malignant transformations were observed.

Conclusions:

• Genetic mutations in EXT1 and EXT2 are confirmed as the primary cause of HME in affected families.
• Early diagnosis and consistent follow-up are crucial for preventing secondary bone deformities and managing complications.
• While malignant transformation risk is low, proactive management can significantly improve patient outcomes.