Achondroplasia

Overview

Achondroplasia is the most common skeletal dysplasia and the leading cause of disproportionate short stature (dwarfism). It is an autosomal dominant genetic disorder caused by mutations in the FGFR3 (fibroblast growth factor receptor 3) gene, leading to abnormal cartilage formation and impaired endochondral ossification.

Clinical features:

• Short stature with rhizomelic limb shortening (proximal arms/legs).

• Macrocephaly with frontal bossing.

• Midface hypoplasia.

• Lumbar lordosis, bowed legs, trident hands.

• Normal intelligence and lifespan (except with severe complications).

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Treatment Options

1. Supportive / Non-Drug Management

• Multidisciplinary care: orthopedics, neurology, pulmonology, ENT, genetics.

• Physical therapy to improve mobility.

• Occupational and social support to optimize quality of life.

• Nutritional management: prevent obesity, which worsens orthopedic complications.

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2. Pharmacological Therapy

• Vosoritide (CNP analog, FDA/EMA approved for children with achondroplasia ≥5 years)

  • Dose: 15 mcg/kg subcutaneous injection once daily.

  • Mechanism: counteracts FGFR3 signaling, improves endochondral bone growth.

  • Monitored by pediatric endocrinology/genetics.

• Investigational therapies:

  • Infigratinib (FGFR1–3 tyrosine kinase inhibitor) under trial.

  • Other CNP analogs in development.

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3. Surgical / Interventional Therapies

• Limb lengthening procedures (controversial, multiple surgeries required).

• Spinal decompression surgery for spinal stenosis or cord compression.

• Corrective osteotomy for severe limb deformities.

• Adenoidectomy/tonsillectomy or tracheostomy in cases of airway obstruction/sleep apnea.

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4. Symptomatic Treatment

• Pain management:

  • Paracetamol 500–1000 mg PO q6h.

  • NSAIDs (ibuprofen 400 mg q8h) as needed for musculoskeletal pain.

• Treatment of recurrent ear infections: appropriate antibiotics (e.g., amoxicillin 500 mg TID for 7–10 days).

• CPAP therapy in obstructive sleep apnea.

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Monitoring & Follow-Up

• Neurological monitoring: hydrocephalus, spinal stenosis.

• Orthopedic assessment: limb deformities, joint pain.

• ENT and audiology follow-up: recurrent otitis media, hearing loss.

• Sleep studies for obstructive sleep apnea.

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Key Notes

• Achondroplasia is not curable, but modern therapies like vosoritide show promise in improving growth velocity in children.

• Life expectancy is generally normal, but complications (spinal stenosis, apnea, obesity-related problems) can reduce quality of life.

• Genetic counseling is important: 80% of cases arise from new mutations, but affected individuals have a 50% chance of transmission to offspring.