X-Linked Disorders: Hemophilia

Hemophilia: An Overview

Written by: Shirah Segal

Hemophilia is an inherited condition in which blood does not clot properly. This can lead to unusual or prolonged bleeding after an injury, as well as internal bleeding. An individual with hemophilia does not make clotting factors, the proteins that help blood cells stick together. Hemophilia can be classified as mild, moderate, or severe, depending on the amount of clotting factors in the blood. There are also two different forms of X-linked hemophilia, based on the deficient clotting factor. Hemophilia A occurs when a person has low levels of clotting factor 8, and Hemophilia B occurs when a person has low levels of clotting factor 9 (35, 36).

The most common symptoms of hemophilia are excessive bruising or bleeding. The intensity of the bruising or bleeding depends on the severity of the condition. Bleeding may occur for no reason or continue for a while after a minor injury. Large bruises may develop under the skin, and internal bleeding may cause joint pain (35, 36).

Hemophilia is caused by a genetic variant in one of the genes that provide instructions for making the clotting factor proteins. Hemophilia A is caused by a variant in the F8 gene, and Hemophilia B is caused by a variant in the F9 gene. Variants involved in the mild to moderate forms of hemophilia cause a lowered amount of clotting factors, while variants involved in severe hemophilia cause a total lack of clotting factors (35, 36, 37)

Hemophilia A in More Detail

Written by: Abigail Sayers

Hemophilia A is a bleeding disorder that can be caused by various pathogenic changes in the coagulation factor VIII gene, F8, of the X chromosome. These changes cause a deficiency in factor VIII clotting activity and although the DNA changes are different from each other, they are attributed to a similar presentation. The clinical signs of this disorder include prolonged or excessive bleeding after procedures and episodes of spontaneous bleeding, such as joint bleeds or deep-muscle hematomas (10). 

• The most common of these changes are inversions of intron 22, which is the reversal of the order of the DNA sequence, and occurs in 40-50% of Hemophilia A patients (9). 

• An inversion of intron 1 occurs in 5-7% of Hemophilia A patients (9). 

• Hemophilia A can also be acquired through a new genetic change rather than passed down from two carrier parents, meaning that it is caused by a de novo pathogenic change in an individual’s DNA.

Because Acquired Hemophilia A is very rare, there is often a delay in diagnosis due to a lack of family history of the disorder (11).

Reviewed and Edited by Rachel Baer, MSc, and Andy McCarty, MS, LGC, CGC

Learn More About Genetics:

• Sample Types

• Prenatal and Fetal Testing

• Aneuploidies

• Cytogenetics

Learn More About the X Chromosome:

• The X Chromosome

• X and Y Chromosomal Aneuploidies

• DMD and BMD

• Red-Green Color Blindness

• Alport Syndrome

• Fabry Disease

• Fragile X Syndrome

• Charcot-Marie-Tooth (CMT)