Genetic conditions are caused by variants in DNA. They can arise for the first time in an individual (de novo) or be inherited from their parents according to different inheritance patterns:
- Autosomal dominant. One copy of the variant is enough for the condition to develop. It affects males and females equally, is often seen in every generation, and each child of an affected person generally has a 50% chance of inheriting the variant.
- Autosomal recessive. Two pathogenic variants in the same gene are required, one in each copy. These may be the same variant or two different variants, usually inherited one from each parent. If both parents are carriers, each pregnancy has a 25% chance of the child having the condition, a 50% chance of being an unaffected carrier, and a 25% chance of inheriting neither variant.
- X-linked dominant. The variant is located on the X chromosome, and one copy is enough for the condition to develop. If the mother is affected, each son or daughter has a 50% chance of inheriting the variant. If the father is affected, all his daughters will inherit it, but none of his sons will.
- X-linked recessive. This is much more common in males, who have only one X chromosome. Females with one copy of the variant are usually carriers without symptoms, although some may develop symptoms, generally mild ones. If the mother is a carrier, each son has a 50% chance of having the condition, and each daughter has a 50% chance of being a carrier. An affected father passes the variant to all his daughters, who will be carriers, but to none of his sons.
- Mitochondrial inheritance. Mitochondrial DNA is inherited exclusively from the mother, so children of an affected mother may inherit the variant, whereas children of an affected father will not.
An important concept is penetrance: the percentage of people with a particular genetic variant who go on to develop the condition. When penetrance is incomplete, not everyone with the variant develops the condition.