Histology · Year 1 · from Histology
Case 2: Achondroplasia
Clinical Image
Source: Wikipedia - Achondroplasia - CC BY-SA 4.0
Case Presentation
A couple is referred for genetic counseling after their 20-week ultrasound reveals shortened fetal long bones. The baby is born at term and examination reveals characteristic features: short stature with disproportionately short limbs (rhizomelic shortening - proximal segments most affected), a relatively normal-sized trunk, macrocephaly with frontal bossing, and midface hypoplasia with a depressed nasal bridge. Neurological examination is normal. Skeletal radiographs show characteristic findings including a narrow spinal canal, squared iliac wings, and short, broad tubular bones with metaphyseal flaring. Genetic testing confirms a G380R mutation in the FGFR3 gene. The parents are counseled that achondroplasia is the most common form of skeletal dysplasia (dwarfism), intelligence is normal, and the condition results from constitutive activation of FGFR3, which normally inhibits chondrocyte proliferation in the epiphyseal growth plate. Follow-up will include monitoring for spinal stenosis and hydrocephalus.
Key Learning Points
- Achondroplasia results from gain-of-function mutations in FGFR3 that inhibit chondrocyte proliferation in the epiphyseal plate
- The epiphyseal plate is organized into zones (reserve, proliferative, hypertrophic, ossification) essential for endochondral ossification
- Because FGFR3 inhibits the proliferative zone, constitutive activation severely limits longitudinal bone growth
- Intramembranous ossification (flat bones of skull) is unaffected, explaining the normal-sized skull but shortened long bones
- The trunk is relatively normal because vertebral growth is less dependent on appendicular growth plate activity