A 3-year-old child has short stature, proximal limb shortening (rhizomelia), a large head with frontal bossing, midface hypoplasia, and trident hand. Intelligence is normal. Spinal stenosis is a known complication. Molecular diagnosis reveals a gain-of-function mutation in FGFR3. What is the inheritance pattern?
- A Autosomal dominant with most cases arising de novo ✓
- B Autosomal recessive
- C X-linked recessive
- D Mitochondrial inheritance
Correct answer: A. Autosomal dominant with most cases arising de novo
Explanation
Achondroplasia is caused by a specific gain-of-function mutation in FGFR3 (fibroblast growth factor receptor 3), which constitutively inhibits chondrocyte proliferation. It follows an autosomal dominant inheritance pattern, but approximately 80% of cases arise as de novo mutations, most commonly associated with advanced paternal age. Both parents being achondroplastic produces lethal homozygous achondroplasia (stillbirth/early neonatal death). Intelligence is normal. Spinal stenosis and foramen magnum stenosis are serious complications requiring surveillance.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.