Hemophilia Inheritance: Inheritance Patterns in Hemophilia
Hearing the term hemophilia for the first time, some of us may ask who that is rather than what it is. So,starting off with inheritance patterns may not be the best approach. Before getting into the actual patterns of how hemophilia is passed through the generations, it might be wise to first discuss what it actually is.
What is hemophilia?
The dictionary definition of hemophilia is ‘love of blood’ which was suggested for it by a medical treatise in 1828. This is rather ironic because any hemophiliac will assure you that their feelings toward the disease are far from love. Hemophilia has been referred to as a ‘royal disease’ because it was prominent among European royalty in the 19th and 20th centuries. So, what is it? Before getting into the definition of the disease, it is important to understand a few things about blood first before understanding this bleeding disorder.
Blood has two parts: one solid and one liquid part that is referred to as plasma. Red blood cells that transport oxygen and white blood cells that help fight infection as well as platelets that help coagulation make up the solid state. The liquid part is composed of proteins, salts, sugars,and water. Clotting is a process that is guided by 14 different proteins that are called clotting factors, their anomalies being a sea of several blood disorders. One of them is hemophilia, which is also known as a blood clotting disorder. More specifically, it impairs the body’s process of making blood clots, which is important to stop bleeding. Stopping bleeding is kind of an important procedure and anything that impairs that process may lead to too much bleeding and death. Individuals that have severe hemophilia have symptoms such as bleeding longer after injury, easy bruising as well as an increased risk of bleeding inside joints or the brain. Again, kind of a big bad deal.
Genetics and Inheritance
Let’s talk about inheritance first before tying it to hemophilia. Females have two X chromosomes while males have one X and one Y chromosome. Upon fertilization of an egg, the female passes on one of her X chromosomes and the male passes on either his X or his Y. In the case of the former, the child will be a girl, while in the case of the latter, the child will be a boy.
Hemophilia is a genetic bleeding disorder. It is hereditary, and it affects mostly men. It is also linked to a defect in the X chromosome. So ironically confusing. In 1803, John Conrad Otto, a Philadelphian physician described it as follows, “About seventy or eighty years ago, a woman by name of Smith, settled in the vicinity of Plymouth, New Hampshire, and transmitted the following idiosyncrasy to her descendants. It is one, she observed, to which her family is, unfortunately, subject and had been the source not only of great solicitude but frequently the cause of death. If the least scratch is made on the skin of some of them, as mortal a hemorrhage will eventually ensue as if the largest wound is inflicted. (…) So assured are the members of this family of the terrible consequences of the least wound, that they will not suffer themselves to be bled on any consideration, having lost a relation by not being able to stop the discharge occasioned by this operation.”
In other words, he recognized that it was a genetic disease as he realized that it was passed down from parent to offspring. He also realized that it was passed down by healthy females as well as that it affected mostly males.
He was right.
So what about these inheritance patterns? Given that hemophilia is X-linked, a female who is a carrier is healthy as she has one X-linked mutation and another healthy X chromosome that compensates for the lack and does not result in blood clotting issues. In males, that is a different situation. When a carrier woman passes down her X-linked mutation to a male, he does not have another healthy X-chromosome to compensate for the lack. The Y-chromosome cannot do that, which is why hemophilia affects males a lot more frequently than females. Female hemophiliacs do exist, but only when both the mother is a carrier and the father actually has hemophilia and the two make a female baby. This is because the disease is recessive, meaning that symptoms are only apparent when females have two copies of the mutation. On the other hand, for males to have the disease, it is enough for the mother to be a carrier. One copy of the mutation on the X chromosome is enough to cause disease in males.
Add to this the fact that about 30% of the disease is a de novo mutation, meaning that it affected an individual spontaneously without prior hemophilia inheritance history.
Given that the disease is marked by a problem with blood clotting, it should come as no surprise that the symptoms are related to a lot of frequent bleeding situations such as frequent internal bleeding and hemorrhage, which can occur spontaneously or as a result of a bump or an injury. As the amount and frequency of these bleeding episodes vary from person to person, hemophilia has been put into three different categories that each differ based on the severity, namely severe, normal and mild hemophilia. Some hemophiliacs bleed only once a month, while others with more severe hemophilia are affected much more frequently such as several times a week.
The number of hemophiliacs who are leading normal lives has increased drastically over the last 50 years or so thanks to clotting factor concentrate. The treatment comes in little bottles that can be stored at home and it is used in the case of a bleeding. As with many diseases, hemophilia has both physical as well as psychological effects on those who have it, which is why a combination treatment along with awareness is of utmost importance for long-term success.