A couple has a child with achondroplasia. Both parents have normal height and clinically normal and neither has a family history of achondroplasia.
1. What is the probable explanation for achondroplasia in their child?
Achondroplasia is a genetic disorder caused by missense mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. About 80% of patients are caused by new mutation or de novo mutation which commonly happens during spermatogenesis and risk increases as paternal age increases. The rest of the cases are inherited through autosomal dominant pattern.
2. What is the risk of recurrence in other children of this couple?
For unaffected parents with a child affected with achondroplasia, the risk for recurrence in their future children is low but probably higher than for the general population because mosaicism involving the germline, although extremely rare in achondroplasia, has been documented (Thompson & Thompson, Genetics in Medicine, 8th Edition). Accordingly, the recurrence rate for a couple that have a child with a genetic disease caused by a de novo mutation is higher than that of the general population and is estimated at 1%–4% (Campbell et al., 2014)
3. If the husband has another child by a different mother, what would the risk of achondroplasia be in that child?
The risk would be lower since the father had a first child with de novo mutation.
4. What is the risk that any offspring of the affected child will also have achondroplasia?
A person who has achondroplasia who is planning to have children with a partner who does not have achondroplasia has a 50 percent chance, with each pregnancy, of having a child with achondroplasia. When both parents have achondroplasia, the chance for them, together, to have a child with normal stature is 25 percent. Their chance of having a child with achondroplasia is 50 percent. Their chance for having a child who inherits the gene mutation from both parents (called homozygous achondroplasia - a condition that leads to death) is 25 percent (https://www.genome.gov/Genetic-Disorders/Achondroplasia).