Understanding Inherited Genetic Disorders

Our bodies are built using instructions stored in our DNA. You can think of DNA as a very large instruction book, and genes as smaller sections inside it that tell the body how to grow, develop and work. We usually get one copy of each gene from our mother and one from our father. Sometimes a gene contains a change that affects how the body works. If that change causes a health condition and can be passed from parent to child, it may cause an inherited genetic disorder.

Examples include beta thalassemia, cystic fibrosis and lysosomal storage disorders. Having an inherited genetic disorder does not mean that anyone did something wrong. These conditions come from the way genes are naturally passed through families.

For many recessive disorders, a person needs to inherit a changed copy of the same gene from both parents to develop the condition. A person with only one changed copy is usually called a carrier. Carriers are often completely healthy and may never know unless they are tested, someone in the family is diagnosed, or they have a child with the condition. This is why a disorder can seem to appear suddenly in a family: the gene change may have been present for generations.

If both parents carry the same recessive condition, each pregnancy usually has:

• a 25% chance that the child has the condition
• a 50% chance that the child is a healthy carrier
• a 25% chance that the child neither has the condition nor is a carrier

These chances start again with every pregnancy. It does not mean that exactly one in every four children will have the disorder. Having one affected child does not make the next child automatically affected, and having one healthy child does not remove the risk for the next pregnancy.

• Recessive: a child usually needs a changed gene copy from both parents, for example beta thalassemia and cystic fibrosis.
• Dominant: one changed copy can be enough to cause the disorder, so an affected parent may pass it on. Some forms of Ehlers-Danlos syndrome follow this pattern.
• X-linked: the condition is linked to the X chromosome and can affect boys and girls differently. Haemophilia and Duchenne muscular dystrophy are examples.

Biological relatives share some of the same genes because they have common ancestors, so they are more likely than unrelated people to carry the same recessive gene change. If they have a child together, there is a greater chance the child inherits the changed gene from both sides of the family.

Cousin marriage does not create genetic disorders; the gene change was already in the family. Many children of related parents are healthy, and unrelated parents can both be carriers too, especially for conditions that are common in a population, such as beta thalassemia in Pakistan. Testing and family history tell you far more about risk than the relationship alone.

• Diagnostic testing: used when someone already has symptoms, to find out whether a genetic condition is the cause.
• Carrier testing: shows whether a healthy person carries a gene change for a recessive disorder.
• Testing during pregnancy: certain tests can check for specific genetic conditions.
• Testing before pregnancy: some couples choose carrier testing before having children, particularly when there is a family history.