Haemophilia Heredity and Inheritance

The factor VIII gene

The gene for factor VIII is located on the X chromosome (locus Xq28), is 186,000 bp long (0.1% of the entire X chromosome), and contains 26 exons. The protein encoded by this gene is composed of 2,351 amino acids with a total relative mass of 267,039 daltons.

Inheritance of haemophilia

The location of the factor VIII gene on the gonosome (X chromosome) determines the recessive mode of inheritance of the disease. Women are very rarely affected, and most often have a carrier state, i.e. the presence of a single mutated allele that they can pass on to their offspring. Only boys are affected; rarely, a female with haemophilia may occur if her father had haemophilia and her mother was a carrier.

Practical implications

As a practical matter, it is essential that all the sons of a man with haemophilia will be healthy and all his daughters will be carriers. 50% of the sons of a carrier mother will be healthy and 50% will have haemophilia. Half of their daughters may also be carriers and half will be healthy women.

New mutations

About 20-30% of people with haemophilia have a negative family history. In this case, either the mutation is newly acquired or the condition has been passed down for generations only by female carriers, without clinical manifestations of the disease.

The manifestations of haemophilia, i.e. the extent of the condition, history and clinical course, as well as the factor level, are a direct expression of the genetic defect and tend to be the same in members of the same family. The disease occurs worldwide and no racial dependence has been found.

Haemophilia carriers

Haemophilia carriers are women who carry a mutated gene on one of their two X chromosomes. Although traditionally considered "healthy carriers", many carriers have reduced clotting factor levels (VIII or IX) and may experience increased bleeding — particularly heavier menstrual bleeding, postpartum haemorrhage, bleeding after surgery or dental procedures. Every carrier should have their clotting factor level measured and be under the care of a haematologist, especially when planning surgery or pregnancy.

Genetic testing and counselling

Modern genetic methods allow the identification of the specific mutation causing haemophilia in a family and subsequent targeted testing of other female family members for carrier status. Genetic counselling is a key component of care for families with haemophilia. Prenatal diagnosis (chorionic villus sampling or amniocentesis) can determine whether a foetus is affected by haemophilia as early as the first trimester of pregnancy. Genetic counselling at a haemophilia centre is recommended before a planned pregnancy.

Further information

• What is haemophilia
• Haemophilia treatment
• Von Willebrand disease — a related bleeding disorder