Multiple Hereditary Exostoses

Multiple Hereditary Exostoses (MHE) is characterized by multiple osteochondromas.

• Genetics: Autosomal dominant. EXT1 or EXT2 mutations (tumor suppressor genes).
• Incidence: 1 in 50,000.
• Pathophysiology: Loss of EXT function leads to abnormal cartilage growth at physes → osteochondromas.
• EXT1 vs EXT2: EXT1 mutations (chromosome 8) typically cause more severe phenotype than EXT2 (chromosome 11).
• Natural History: Lesions grow until skeletal maturity, then stop. Malignancy risk persists lifelong.

Osteochondroma Structure

• Cartilage-capped bony outgrowth arising from the metaphysis.
• Continuous with host bone cortex and medulla.
• Grows away from the adjacent joint (important for diagnosis).
• Cartilage cap: Normally less than 1cm in adults, greater than 2cm concerning for malignancy.

Why Deformity Occurs

• Osteochondromas at the distal ulna → ulnar shortening → radial bowing.
• Tethering effect on growth plate.
• Similar mechanism at ankle (fibular lesions) → ankle valgus.

Common Sites

• Distal femur (most common).
• Proximal tibia.
• Proximal humerus.
• Distal ulna/radius (causes forearm deformity).

History:

• Age of first lesion.
• Symptomatic lesions (pain, cosmesis, nerve compression).
• Family history.
• Any new pain or growth in adults (malignancy concern).

Physical Exam:

1. Palpable Masses: Typically at metaphyses.
2. Deformity: Forearm (short ulna), ankle (valgus).
3. ROM: Limited by impingement.
4. Neurovascular: Peroneal nerve at knee, etc.

Imaging:

• X-ray: Multiple osteochondromas, broad-based or pedunculated.
• MRI: If malignancy suspected (cartilage cap thickness greater than 2cm or irregular).

Genetic:

• EXT1/EXT2 testing if diagnosis uncertain.

• Simple Excision: Early mobilization, wound care.
• Forearm Reconstruction: Splinting, protected ROM.
• Lengthening: Fixator care, daily adjustments.
• All Patients: Continue surveillance for other lesions.

• Most lesions remain benign.
• Malignant transformation: 1-5%.
• Significant deformity may limit function.

• Routine surveillance imaging: No consensus on whether asymptomatic adults need scheduled whole-body MRI/screening. Some advocate baseline imaging of axial/proximal lesions (pelvis, shoulder) that are hard to monitor clinically; others rely on symptom-driven imaging and patient education. Porter's data suggest EXT1 carriers may justify more proactive screening.
• Timing of forearm reconstruction: Whether early excision and ulnar lengthening prevent radial head dislocation, versus observation until deformity declares itself, remains debated; high-quality comparative evidence is limited.
• True malignant transformation rate: Quoted figures range from 0.5% to 5%; older series likely overestimated risk through referral bias, while genotype (EXT1) and lesion location modify individual risk.
• Guided growth vs osteotomy: Optimal first-line correction of knee/ankle valgus (hemiepiphysiodesis versus corrective osteotomy) depends on remaining growth and deformity magnitude, without firm thresholds.
• Emerging medical therapy: Heparan-sulphate pathway and palovarotene-type signalling research is experimental; no disease-modifying drug is established in practice.

Global epidemiology

• Prevalence approximately 1 in 50,000 worldwide, with a male predominance (~1.5:1) and near-complete penetrance (~96%); roughly 10% of cases arise de novo without a family history.
• Mean number of osteochondromas per patient is 15-18; lesions appear and enlarge in the first decade and cease at physeal closure.

Consensus and society guidance (side by side)

Registry and network evidence

• No dedicated arthroplasty-style registry exists; long-term data derive from population databases (e.g. Schmale's Washington kindreds), tertiary bone-tumour registries and rare-disease networks (Orphanet, EuroBoNeT/European sarcoma networks).

High- vs limited-resource practice

• Well-resourced settings: MRI surveillance, genetic testing, guided growth (8-plates), staged forearm reconstruction and limb salvage for transformation.
• Limited-resource settings: diagnosis is clinical/radiographic; emphasis on educating patients about warning signs (new pain, growth after maturity, enlarging cartilage cap) and timely referral when malignancy is suspected, since chondrosarcoma is chemo- and radio-resistant and depends on adequate surgical margins.

Multiple Cartilaginous Lesions:

Key Distinguishing Points:

• MHE: Metaphyseal, cortex continuous with host bone.
• Enchondromas (Ollier): Medullary, radiolucent with stippled calcifications.
• DEH (Trevor Disease): Single limb, epiphyseal involvement.
• Malignancy risk: MHE 1-5%, Ollier 25-30%, Maffucci 25-30%.