Did you know that hemophilia is a rare genetic disorder that affects approximately 1 in 10,000 people worldwide? If you're a woman or assigned female at birth, you may not even know you're a carrier until you have a son with hemophilia, as it's passed down through the X chromosome. In this article, we'll explore the inheritance patterns of hemophilia and how you can determine if you're a carrier.
What Is Hemophilia?
Hemophilia is a rare genetic disorder that affects the body's ability to form blood clots, which are necessary to stop bleeding after an injury.
People with hemophilia have a deficiency or dysfunction of specific proteins in their blood called clotting factors, which can cause prolonged bleeding and slow or incomplete healing.
Uncontrolled bleeding into the joints, muscles, brain, or other internal organs can result in serious complications.
Severe forms of hemophilia can result in spontaneous bleeding. However, milder conditions may not result in spontaneous bleeding and thus may be difficult to diagnose until surgery or a severe injury.
Types Of Hemophilia
The two major types of hemophilia are:
- Hemophilia A - Factor VIII deficiency
- Hemophilia B - Factor IX deficiency
Even though both types present with similar symptoms, they are caused by mutations in different genes.
What Causes Hemophilia?
Those with hemophilia have a deficiency of either factor VIII or factor IX, critical proteins required for blood clotting.
The F8 and F9 genes contain instructions to produce these two proteins.
Factor VIII and factor IX proteins work together to seal off blood vessels damaged during an injury to minimize blood loss.
Changes or variants in the F8 and F9 genes can result in the production of abnormal versions or insufficient levels of the coagulation proteins.
This can lead to problems in the blood clotting process and result in uncontrolled bleeding.
In severe hemophilia, the coagulation proteins are completely absent; in mild hemophilia, the activity of the proteins is reduced.
Acquired hemophilia is not a result of genetic variants. It occurs when the body’s immune system starts attacking factor VIII - an autoimmune disorder.
Hemophilia Inheritance
Hemophilia A and hemophilia B are inherited in an X-linked recessive pattern.
The F8 and F9 genes are located on the X chromosome, one of the sex chromosomes.
People assigned males at birth have one copy of the X chromosome and one copy of the Y chromosome.
Due to this, even one copy of the altered F8 or F9 gene can result in hemophilia in males.
People assigned females at birth have two copies of the X chromosome.
So even if they have one copy of the altered genes, the normal copies on the other X chromosome can compensate for the lowered activity.
Hence, in most cases (except for X-inactivation), they may not have hemophilia, even if they have a copy of the altered gene. Therefore they are “carriers” of hemophilia.
However, there’s a 50% chance they pass the altered gene copy to their offspring.
If the daughter receives it, she continues to be a carrier; if the son receives it, he will be affected by hemophilia.
Is Hemophilia Inherited From The Mother Or Father?
Hemophilia is typically inherited from the mother.
Hemophilia-causing genes are located on the X chromosome, one of the two sex chromosomes.
If a female carrier has a son, there is a 50% chance that he will inherit the mutated gene and develop hemophilia and a 50% chance that he will inherit the normal gene and not have hemophilia.
If the female carrier has a daughter, there is a 50% chance that she will inherit the mutated gene and be a carrier and a 50% chance that she will inherit the normal gene and not be a carrier.
Who Inherits The Hemophilia Disorder Most Often?
Conditions inherited in an X-linked recessive manner more commonly affect males than females since males only have on the X chromosome.
A daughter will get affected only when an affected father and a carrier mother each pass only the faulty gene copy to the daughter.
What Does It Mean To Be A Carrier Of Hemophilia?
Being a carrier of hemophilia means that a person has a mutated hemophilia gene on one of their X chromosomes but not on the other.
As a result, carriers typically do not experience symptoms of hemophilia themselves.
However, they can pass the mutated gene on to their children.
Female carriers have a 50% chance of passing the mutated gene to each of their children, regardless of their gender.
Since they can pass either their normal X chromosome or their mutated X chromosome to their offspring.
It is important for carriers to be aware of their status, as they may have a higher risk of having a child with hemophilia.
Carriers can be identified through genetic testing, which can detect the presence of the hemophilia gene mutation in their DNA.
Genetic counseling may also be recommended for carriers and their families to help them understand the risks associated with hemophilia inheritance and to make informed decisions about family planning and medical management.
Genetic Testing To Find Out Your Carrier Status Of Hemophilia
A genetic test analyzes a small sample of your blood or saliva to look for changes in the hemophilia genes.
Different types of genetic tests can be used to diagnose hemophilia carrier status.
One common method is called DNA sequencing. This involves reading the entire genetic code of the hemophilia genes to detect any mutations.
Genetic testing can be done before or during pregnancy to determine the risk of having a child with hemophilia.
For example, suppose a woman knows she is a carrier of the hemophilia gene mutation. In that case, she may choose to undergo prenatal testing during pregnancy to determine whether the developing fetus has inherited the mutated gene.
This information can help the parents make decisions about medical management and family planning.
Summary: Hemophilia Inheritance
Hemophilia is caused by gene mutations that provide instructions for making proteins necessary for blood clotting. They are located on the X chromosome. As a result, hemophilia is more commonly inherited by males than females since males have only one X chromosome. Females are usually carriers of hemophilia and can pass the mutated gene on to their children. Genetic testing is a reliable way to determine carrier status and can be done before or during pregnancy. This can help parents make decisions about medical management and family planning. It is often recommended that genetic testing be done in the context of genetic counseling to help individuals and families understand the implications of the results.
Reference
- https://www.cdc.gov/ncbddd/hemophilia/inheritance-pattern.html
- https://www.cdc.gov/ncbddd/hemophilia/course/Hemophilia_Patterns_v3.pdf
- https://medlineplus.gov/genetics/condition/hemophilia/
- https://www.ihtc.org/hemophilia-inheritance-patterns
- https://rarediseases.info.nih.gov/diseases/6591/hemophilia-a
- https://www.ncbi.nlm.nih.gov/books/NBK22260/
