Achondroplasia?

Background: Achondroplasia is a common, nonlethal form of chondrodysplasia. It is transmitted as an autosomal dominant trait with complete penetrance. De novo mutations cause 75-80% of cases. The mutation rate is estimated to be 0.000014 per gamete per generation. Cardinal features include short stature, rhizomelic shortening of the arms and legs, a disproportionately long trunk, trident hands, midfacial hypoplasia, prominent forehead (frontal bossing), thoracolumbar gibbus, true megalencephaly, and caudal narrowing of the interpedicular spaces.


Pathophysiology: Achondroplasia is caused by mutations in the gene for fibroblast growth factor receptor-3 (FGFR3). The gene has been mapped to band 4p16.3. The common mutations cause a gain of function of the FGFR3 gene, resulting in decreased endochondral ossification, inhibited proliferation of chondrocytes in growth plate cartilage, decreased cellular hypertrophy, and decreased cartilage matrix production. G1138A and G1138C mutations account for approximately 99% of the mutations resulting in a specific amino acid substitution (G380R). A rare mutation is the novel missense mutation (Lys650Met) in the tyrosine kinase region, which results in a disorder termed severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN). Another mutation, Gly380Arg, has been reported in a Spanish population.

... is a random genetic mutation that causes dwarfism in humans.