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Amanda Elizabeth Poetiray

9B

Ms. Roxanne Diane R. Uy

Biology

7 November 2018

Case Study: The Royal Disease “Hemophilia”

Known to be one of history’s most iconic monarchs, Queen Victoria has ruled for

more than 60 years. She is associated with Britain’s great age of industrial expansion,

economic progress, and was empress of the world’s largest ever empire, denoting an era of

British history. However, on March 27, 1884, one of Queen Victoria’s sons, Leopold had an

accident at a yacht club in southern France. Though the accident was minor, his injuries

triggered massive internal bleeding and within 24 hours he was dead. Prince Leopold was the

first monarch known to suffer from hemophilia – a blood disorder that causes excessive

bleeding; but he wasn’t the last. Thus, this accident gave birth to what was known to the

world as “The Royal Disease”.

Hemophilia was first introduced to the world as “The Royal Disease” during the reign

of Queen Victoria of England. This is because the hemophilia gene was passed from Queen

Victoria to the ruling families of Russia, Spain, and Germany. Queen Victoria’s gene for

hemophilia was caused by a spontaneous mutation. Apparently, she was a carrier of the

hemophilia gene, more specifically, hemophilia B, or factor IX deficiency, but it was her son,

Leopold, who endured the effects of the bleeding disorder, including frequent hemorrhages,

and debilitating pain. It is reported that hemophilia almost always strikes males more than

females, for reasons that become clear once the genetics of the disease are known, which

explains how Leopold is hemophilic while his sisters, Alice and Beatrice were only carriers.

The way it works is that women inherit two X chromosomes, one from each parent; but men

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get only one X, from their mothers. Thus, the reason why men has a higher chance of getting

hemophilia is because women always inherit two copies always inherit two copies of the

blood-clotting gene, one from each parent, while men get only a single version of the blood-

clotting gene.

Bleeding disorders, particularly hemophilia and von Willebrand disease (VWD)

create large demands on health care resources and can lead to spontaneous internal bleeding

and bleeding following injuries and surgery. Though they are both bleeding disorders, they

are different in several ways. People with VWD have a problem with a protein in their blood

called von Willebrand factor (VWF) that helps control bleeding. VWF helps cells in the

blood, called platelets, mesh together and form a clot to stop the bleeding if a blood vessel is

injured and bleeding occurs. In hemophilia, the inability for blood to not be able to clot

normally is caused by a problem with another type of clotting factor known as factor VIII in

hemophilia A and factor IX in hemophilia B. Our bodies have 13 clotting factors that work

together in this process. Having too little of factors VIII or IX is what causes hemophilia.

Besides that, though both disorders are usually inherited, the inheritance pattern is different.

VWD are inherited in an autosomal dominant pattern, which means one copy of the altered

gene in each cell is sufficient to cause the disorder. Meanwhile, hemophilia A and hemophilia

B are inherited in an X-linked recessive pattern. The genes associated with these conditions

are located on the X chromosome, which is one of the two sex chromosomes.

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Through my research, Queen Victoria is known to be a carrier of hemophilia and

passed this disease to her three children, Alice and Beatrice, whom are also carriers, and

Leopold who is hemophilic. The icon shaded with all red represents those who are

hemophilic, while the icons that are half-shaded represents those who are carriers of the

disease. As observed in the pedigree chart, starting with Alice and Beatrice, since they both

are carriers, it is evident that her children would either be a carrier or inherit hemophilia. The

pedigree chart further verifies this fact as three of Alice and Beatrice’s children inherit the

disease, with a total of three females being carriers and three males being hemophilic.

Furthermore, in terms of Leopold’s children, since he is hemophilic, his children would at

least inherit the disease as well. The pedigree chart further verifies this fact, as his daughter is

a carrier of the disease due to the Leopold’s faulty X chromosome. Therefore, this pedigree

chart can further explain the signs and symptoms of the disease as well as how the disease is

transmitted/inherited from one generation to another and justifies how one faulty gene can

impact a family hugely.

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1st Punnett Square: Affected by the Royal Disease

XH Xh
Queen Victoria & Prince Albert

XH XH XH XHXh Genotypic Ratio: 1:1:1:1

(XHXH = 25%, XHXh = 25%, XHY = 25%,
XhY = 25%)

XHY Xh Y Phenotypic Ratio: 2:2

Y (Female normal = 25%, Female carrier = 25%,
Male normal = 25%, Male hemophilia = 25%)

2nd Punnett Square: Carriers of the Royal Disease

XH XH
Princess Helena & Leopold

Xh XH Xh XH Xh Genotypic Ratio: 2:2

(XHXh = 50%, XHY = 50%)

Phenotypic Ratio: 2:2

H H
Y X Y X Y
(Female carrier = 50%, Male normal = 50%)

3rd Punnett Square: Not Affected by the Royal Disease

XH XH
Alexandra & Edward VII

XH XH XH XH XH Genotypic Ratio: 2:2

(XHXH = 50%, XHY = 50%)

Y XHY XHY Phenotypic Ratio: 2:2

(Female normal = 50%, Male normal = 50%)

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In terms of constructing the Punnett squares, I have divided them amongst members

of the royal family that are affected by the Royal Disease, those who are said to be carriers,

and those who didn’t have the disease. To make it more accurate, I have made the possible

Punnett Squares of Queen Victoria’s children as they are of direct bloodline to where the

disease started and originated from. The first Punnett square shows the possible offspring of

Queen Victoria and Prince Albert and determines who will inherit the disease. As explained

above, there is a 25% chance of the offspring inheriting the disease with its gender being

revealed as a male. The second Punnett square shows the possible offspring of Leopold, who

is Queen Victoria’s son that got inherited with the disease, and his wife Princess Helena of

Waldeck. As shown in the Punnett square, there is a 50% chance of the offspring being a

carrier and the gender would be a female. The third Punnett square shows the possible

offspring of Edward VII, Queen Victoria’s son who is not affected by the disease and his

wife Alexandra. As shown in the Punnett square, there is a 0% chance of the offspring

inheriting the disease.

Though Queen Victoria officially introduced hemophilia to the world, incidences of

excessive or abnormal bleeding were first recorded hundreds of years ago. In the Talmud, a

collection of Jewish rabbinical writings from the 2nd century, it was written that male babies

did not have to be circumcised if two brothers had already died from the procedure. In the

12th century, an Arabian physician wrote of males in a particular village who had died of

uncontrollable bleeding. As mentioned in the previous paragraphs, Princess Alice and

Princess Beatrice, Queen Victoria’s daughters, who were carriers of the disease, as well as

Leopold, went on to marry royalty in other European countries. Leopold’s sons were

unaffected because they got their X chromosomes from their mother. Beatrice’s daughter,

Victoria Eugenie, took the disease to Spain when she married King Alfonso XIII. The couple

went on to have five children: one daughter, who was a carrier and four sons, two of whom

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had hemophilia. In terms of Alice, her son died from the disease in early childhood. One of

her daughters, Irene, married Prince Henry of Prussia and passed the gene to the German

royal family. She gave birth to two sons, one who died at the age of 4 and the other at 56.

Alice’s second daughter, Alix, married Tsar Nicholas II of the Russian royal family.

Unfortunately, all of Alix and Tsar’s children died during the Russian revolution so the

mutant gene was stopped in its tracks.

Oddly enough, Victoria’s mutant gene never made it beyond the fourth generation.

No living member of the present as well as past reigning dynasties of Europe is known to

show symptoms and signs of hemophilia or is believed to carry the gene for it. None of

Victoria’s great-great granddaughters in Spain or Britain inherited it. In Prussia she had only

great-great grandsons, and none of her Russian great-great granddaughters ever had any

children as all four were murdered during the Bolshevik revolution. The last descendent of

Victoria known to suffer from the disease was Infante Don Gonzalo. However, because the

hemophilia gene remains hidden in females who only inherit the gene from one parent, there

remains a small chance that the disease could appear again, especially among the female-line

Spanish descendants of Princess Beatrice. Hemophilia today is not as fatal a diagnosis.

However, Queen Victoria’s family possessed the disease in a time where technology and

medical advances exist. They certainly could have never imagined the drastic impact this one

tiny mutation could have on the entire course of European history. The disease, obviously,

caused Queen Victoria’s families across Europe unimaginable pain, and this serves as an

incredible example of genetics and how it can impact a family and their offspring for

generations to come.

I believe that taking part in genetic counseling, as a prerequisite to marriage is totally

fine as the whole idea of it is just to provide information and support to families affected by

or at risk of a genetic disorder. To avoid passing down any sort of disease, I believe that it is

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essential to seek genetic counseling so then they don’t have to spend much expenses for

medication or bear with the burden knowing that their child has been passed down with a

genetic disorder that might be deadly such as hemophilia, as discussed in the previous

paragraphs. Personally, in my own beliefs, I wouldn’t want my child to be burden with a

disease that will make them suffer when I was already aware that I could make a change in

that by taking genetic counseling. Besides just knowing what birth defects run either in my

family or my other significant other’s family, taking genetic counseling would make me more

aware of myself and what actually runs in my genes. Just like how Queen Victoria didn’t

know that she had hemophilia, it would be good to check on what actually runs in my genes

or my significant other’s genes and if there really are any gene defects or not. Personally, I

would want to know what goes around my genes despite if I have any gene disorders or not.

It would also be nice to know more about my family’s history and what is at risk.

As a student, I believe that case studies are fundamental in order to study the field of

genetics because case study research generates a large amount of data from multiple sources.

Case study research excels at bringing us to an understanding of a complex issue or object

and can extend experience or add more knowledge to what is already known through

previous researches done. Through case studies, it gives us access to gather in depth

information about a specific person, group, community or event. The field of genetics covers

a lot of topics, as it is one of the most rapidly developing fields of biology. Genetics is

essential to understanding all aspects of biology, and this field has driven many of the

modern advances in medicine, agriculture, and the pharmaceutical industry. Besides that,

case studies can provide very detailed information about a particular subject that it would not

be possible to acquire through another type of experimentation. Therefore to conclude, I

believe that doing this activity was very beneficial for me as a student as it gives me a better

understanding on the advantages and benefits of using a case study when researching about a

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complex topic such as hemophilia or “The Royal Disease”. By just doing this case study, I

have learned a lot regarding the history, how it happens and how it is passed on and also

learned other skills such as applying knowledge on Pedigree charts in tracking how the Royal

Disease was inherited and explained the occurrence of the disease using Punnett Squares and

model of inheritances. Not only did I accomplish this task by using the knowledge that I

already have, I also gained new understandings in the field of genetics and the history of

hemophilia.

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Works Cited

“Frequently Asked Questions.” VWD - Frequently Asked Questions - World Federation of

Hemophilia, www.wfh.org/en/page.aspx?pid=680.

“Hemophilia - Genetics Home Reference - NIH.” U.S. National Library of Medicine,

National Institutes of Health, ghr.nlm.nih.gov/condition/hemophilia#inheritance.

“Hemophilia: The Royal Disease.” Chicago Health, 4 Feb. 2016,

chicagohealthonline.com/hemophilia-the-royal-disease/.

“History of Bleeding Disorders.” National Hemophilia Foundation, 27 Feb. 2017,

www.hemophilia.org/Bleeding-Disorders/History-of-Bleeding-Disorders.

“History of Hemophilia: The Royal Disease.” ARJ Infusion Services, 30 Mar. 2018,

www.arjinfusion.com/a-look-back-at-the-history-of-hemophilia-the-royal-disease/.

“Queen Victoria and The Royal Disease.” College of Liberal Arts, 1 May 1970,

cola.unh.edu/anthropology/queen-victoria-and-royal-disease.

“The Royal Disease.” Mental Floss, 27 Oct. 2009, mentalfloss.com/article/23112/royal-

disease.

“Variations.” 23andMe AU, DE, FR & EU - Variations: The Royal Disease,

www.23andme.com/en-int/gen101/variation/hemophilia/.

“Von Willebrand Disease - Genetics Home Reference - NIH.” U.S. National Library of

Medicine, National Institutes of Health, ghr.nlm.nih.gov/condition/von-willebrand-

disease#inheritance.

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