As part of a clinical placement you are visiting a teenager who has had continuing respiratory infections since birth due to cystic fibrosis. The boy’s problems are not limited to his respiratory system. His body weight is very low, and he has a long history of suffering from diarrhea. The boy’s parents meet you at the door with their daughter. The daughter has been tested and found to have cystic fibrosis but her clinical symptoms are far less severe than those of her brother. How could this occur?

Cystic fibrosis is an autosomal recessive disease. Because it is autosomal recessive affected children must have received one copy of the disease gene from each of their parents. Only children who are homozygous for the gene can be affected. Their parents can be unaffected carriers meaning they have one copy of the disease gene and one copy of the normal gene. Because the condition is autosomal both boys and girls equal risk of being affected. Although statistically there is a 25% chance of a child of parents who are cystic fibrosis carriers developing the disease, in this example both children have been affected. This is possible because the genes acquired at conception of one child are not affected in any way by the genes that have been inherited by previous children. The daughter can be less severely affected than the son because of variable penetrance. Variation in penetrance means that people who have the same gene is present (genotype) will not necessarily have the same level of disease-in other words there phenotypes will vary. This tells us that simply looking at the genes that a person has may not give us the full story about their risk of developing disease.