Achondroplasia is the most common form of disproportionate short-stature skeletal dysplasia. It is a genetic disorder characterized by impaired endochondral ossification, leading to shortened proximal limbs, macrocephaly, and distinct craniofacial features.

Achondroplasia is caused by a gain-of-function mutation in the FGFR3 gene on chromosome 4p16.

1. Approximately 80% of cases arise from de novo mutations, while 20% are inherited in an autosomal dominant pattern.

The mutation leads to the constitutive activation of Fibroblast Growth Factor Receptor 3, which negatively regulates chondrocyte proliferation and differentiation in the growth plate. This impairs longitudinal bone growth, primarily affecting long bones.

The prevalence is approximately 1 in 15,000 to 40,000 live births. It affects both genders equally and occurs across all ethnic groups.

Advanced paternal age is a primary risk factor for de novo mutations.

A. Early Symptoms

• Disproportionately large head (macrocephaly)


• Prominent forehead (frontal bossing)


• Hypotonia (infancy) B. Common Symptoms


• Shortened proximal extremities (rhizomelia)


• Trident hand configuration


• Lumbar lordosis C. Advanced Symptoms


• Spinal stenosis


• Obstructive sleep apnea


• Genu varum (bowed legs) D. Emergency Symptoms


• Cervicomedullary compression


• Acute respiratory distress

Inspection reveals rhizomelic shortening, midface hypoplasia, and a depressed nasal bridge. Palpation may show kyphosis or limited extension at the elbows.

A. Clinical Assessment: Based on physical phenotype.
B. Laboratory Testing: Generally not required for diagnosis.
C. Imaging Studies: Skeletal survey.
D. Functional Tests: Polysomnography.
E. Biopsy Findings: Not indicated.
F. Genetic Testing: FGFR3 molecular testing.
G. Differential Diagnosis: Hypochondroplasia, thanatophoric dysplasia.

Test Name: FGFR3 Mutation Analysis
Type: Blood Test
Purpose: Confirm diagnosis
Expected Findings: Pathogenic variant
Interpretation: Confirms achondroplasia