The genetics of achondroplasia

In the novel Stones from the River by Ursula Hegi, the reader follows a young girl with achondroplasia on her journey to adulthood. This character is unusually perceptive and draws the community around her in a sparkling web of storytelling. The popular show on TLC features the Roloff family, in which the father has a form of dwarfism known as diastrophic dysplasia and the mother has achondroplasia. Diastrophic dysplasia results from an autosomal recessive allele and achondroplasia results from an autosomal dominant allele.

Notably, dominance and recessiveness are terms which refer to how alleles act, not predominance in the population. In the case of achondroplasia, the homozygous dominant genotype results in a lethal phenotype. These fetuses are stillborn or die shortly after birth. The phenotype is determined by a dominant allele that interferes with bone growth during development. This dominant allele codes for a mutation in the fibroblast growth factor receptor gene 3 (FGFR3), resulting in abnormal cartilage formation. Typically, FGFR3 inhibits bone growth. In people with achondroplasia, the mutated form of the receptor is constitutively active. This hyperactive signaling pathway leads to shortened bones. In most cases, people with the condition are born to normal parents; achondroplasia typically results from a new mutation. Unfortunately, human growth hormone does not help people with achondroplasia.

For more, see An Introduction to Genetic Analysis by Griffiths et al. (6^th edition).