Achondroplasia

Achondroplasia is one of the most common and recognized short-limbed skeletal dysplasias, with a prevalence of 1 in 26,000 to 28,000 live births. Although achondroplasia is inherited in an autosomal dominant manner, 80% of affected children have a de novo mutation. The FGFR3 gene is the only gene associated with achondroplasia. Two mutations in this gene account for 99% of cases; both result in an amino acid change (glycine to arginine), which results in continuous activation of the FGFR3 protein. Having a constantly active FGFR3 protein leads to the inhibition of chondrocyte proliferation, which, in turn, inhibits bone growth. The average adult height for patients with achondroplasia is 131 cm for a man and 124 cm for a woman.

Achondroplasia should be considered prenatally if shortened long bones (usually <5th percentile) are noted on third trimester ultrasonography. Some studies have seen a distinctive “collar hoop” sign wherein there is a small bony protuberance at the interface between the femoral metaphysis and the diaphysis. The metaphysis is poorly ossified as well. Prenatal molecular testing of FGFR3 can confirm the diagnosis.

A neonate with achondroplasia may have physical features that are characteristic of the condition: rhizomelic (proximal) shortening of the upper and lower extremities, with extra skin creases at the knees and elbows; short fingers with a trident configuration of the hand (the second, third, and fourth digits seem similar in length and are splayed); and macrocephaly with frontal bossing and a depressed nasal bridge. Because 20% of neonates with achondroplasia may not have these …