What Are the Genetics of Hemophilia?

Hemophilia is a rare, life-long bleeding disorder. It affects people from all racial and ethnic groups. It is caused by a problem in one of the genes that tells the body to make clotting proteins. The clotting proteins, factors VIII (8) or IX (9), are reduced in someone who has hemophilia.

What Causes Hemophilia?

A Family History

Hemophilia can be inherited. This means that it is passed from a parent to a child through genes. Genes are bits of information inside cells that determine a person’s traits or characteristics.

A New Genetic Change

• A baby can have a new genetic change, which was not passed down from a parent.
• The change becomes permanent.
• It can then be passed down to future children.
• 30% of people with hemophilia get hemophilia from a new change in a gene.

What Are Chromosomes?

Our body is made of many cells. Inside most of those cells are chromosomes. Most people have 23 pairs of chromosomes (or 46 total). We get half of our chromosomes from our mother and half from our father. Chromosomes are thread-like strands that contain genes. Genes determine our physical traits, like the color of our eyes.

Understanding Inheritance

• The chromosomes that determine sex (if someone will be male or female) are X and Y.
• Usually, a female has chromosomes of XX and a male has chromosomes of XY.
• The genes that cause hemophilia are located on the X chromosome.
• A female gets an X chromosome from her mother and an X chromosome from her father.
• A male gets an X chromosome from his mother and a Y chromosome from his father.
• Since males have only one X chromosome:
• They will have hemophilia if they have a change in the gene that causes it
• They will always show symptoms of hemophilia if they get the hemophilia gene

When is a Female a Hemophilia Carrier?

Females have two X chromosomes. They could carry the gene that causes hemophilia on one X chromosome, while the other chromosome is normal. Most females that carry the hemophilia gene do not have symptoms of hemophilia. About 10% of females who are carriers do have bleeding symptoms or lower factor levels.

A female is always a carrier when she is:

• The biological daughter of a male with hemophilia
• The biological mother of one son with hemophilia and has at least one other relative with hemophilia
• The biological mother of more than one son with hemophilia

A female may or may not be a carrier when she is:

• The biological mother of one son with hemophilia
• The biological grandmother of one grandson with hemophilia
• An aunt, niece or cousin of a male relative with hemophilia
• A sister of a male with hemophilia

When a mother is a carrier, what are the chances of having a child with hemophilia?

A female who is a carrier can expect one of four possible outcomes with a pregnancy:

• A female child who is not a carrier (25% chance)
• A female child who is a carrier (25% chance)
• A male child with hemophilia (25% chance)
• A male child without hemophilia (25% chance)

The Role of a Genetic Counselor

• Explains how hemophilia is passed down from parent to child
• Draws a family tree to show who is at risk for having a bleeding disorder or being a carrier
• Talks to families about:
• Family planning
• Genetic testing
• Carrier testing

What Is Genetic Testing?

• Testing blood or saliva samples to look for a change in the factor VIII (8) or IX (9) gene
• Tells you about the exact change in the gene that is causing the condition
• It is rare, but sometimes a person with hemophilia has genetic testing results that are negative or uncertain
• This person still has hemophilia, but our testing is not able to find the genetic cause
• Genetic testing can also be done for female relatives of a person with hemophilia
• This kind of genetic testing is called carrier testing

Carrier Testing

• There are two different tests that can be done to see if someone is a carrier for hemophilia.
• Measuring clotting factor levels in the blood
• This test is not perfect. Females can be carriers even if their factor levels are normal. However, if the levels are low, it is highly likely that person is a carrier and has hemophilia herself.
• Genetic testing
• It is best if we know exactly what genetic change is causing hemophilia in the female’s family. We recommend that a male relative with hemophilia gets testing first. However, if there is no male relative available, we can still do genetic testing for carriers.

When Should Carrier Testing Be Done?

• There is no right age to do carrier testing.
• Often, families will wait until their child is old enough to understand and make an informed decision on the testing. This age is usually in the teenage years.

Recommendations for Possible Carriers

• Females who may be carriers should get their clotting factors tested before a surgery or procedure.
• Females who may be carriers should receive testing before they become pregnant so that they understand the risks.
• Females who are carriers should talk to their doctors about how to prepare for pregnancy and delivery.

Planning for a Delivery as a Carrier

• Our treatment center will work with your doctor to make a delivery plan that prevents bleeding for you and your baby.
• A mother who is a carrier has a 50% chance of having a son with hemophilia. If you are having a male child (or the sex of the baby is unknown), we will work with your medical team to make a plan to:
• Have the baby tested for a bleeding disorder soon after birth
• Avoid injections or surgeries (circumcision) until the baby’s test results are known
• Coordinate care for your child at our treatment center if they do have a bleeding disorder
• Help support and prepare you for being a parent of a child with a bleeding disorder

For questions about genetic counseling and the genetics of hemophilia, contact the HTC at 513-517-CBDI (2234) or the at Division of Human Genetics 513-636-4760.