Hereditary Multiple Exostoses: A Narrative Review of Clinical Spectrum, Molecular Pathogenesis, Diagnostic Advances, and Emerging Therapeutic Approaches

Hereditary Multiple Exostoses (HME), also known as multiple osteochondromas, is a rare autosomal dominant skeletal disorder characterised by multiple benign cartilage-capped bony outgrowths that develop along the metaphyses of long and flat bones. Clinically, HME presents as palpable lesions, which are usually painless, but complications such as mechanical pain, skeletal deformities, joint restriction, neurovascular compression, and, rarely, malignant transformation to chondrosarcoma can occur. Classical radiography remains the first-line diagnostic tool, while advanced imaging modalities, including Magnetic Resonance Imaging (MRI), Computed Tomography (CT), whole-body MRI, and PET/CT, are used to detect complex lesions and early signs of malignancy. Uncertain cases can be confirmed by molecular analysis of EXT1/EXT2 genes and Next-Generation Sequencing (NGS). Treatment is largely symptomatic and includes surveillance, surgical resection, and corrective orthopaedic procedures for deformities. Emerging disease-modifying agents, such as palovarotene and heparanase inhibitors, may alter osteochondroma formation, as suggested by preclinical trials. This narrative review summarises current knowledge on the clinical spectrum of HME, its pathogenesis, diagnostic methods, treatment options, and emerging therapeutic approaches.