Achondroplasia results from a gain-of-function mutation in FGFR3. The skeletal phenotype is produced because the mutant receptor constitutively inhibits which cellular process in the epiphyseal growth plate?

• A Chondrocyte proliferation and hypertrophy ✓
• B Osteoblast differentiation from perichondrial cells
• C Osteoclast-mediated remodelling of the primary spongiosa
• D Vascular invasion of the cartilage canals

Explanation

FGFR3 normally restrains growth plate cartilage; activating mutations cause ligand-independent signalling that suppresses proliferation of chondrocytes in the reserve and proliferative zones, shortening all bones formed by endochondral ossification while membranous bones are spared. Osteoblast, osteoclast and vascular events are secondary and unimpaired, which is why intramembranously ossified calvarial bones remain normal.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.