Haemophilia in European royalty

Hemophilia figured prominently in the history of European royalty in the 19th and 20th centuries. Britain's Queen Victoria, through two of her five daughters (Princess Alice and Princess Beatrice), passed the mutation to various royal houses across the continent, including the royal families of Spain, Germany and Russia. Victoria's son Prince Leopold, Duke of Albany suffered from the disease. For this reason, hemophilia was once popularly called "the royal disease". Tests of the remains of the Romanov imperial family show that the specific form of hemophilia passed down by Queen Victoria was likely the relatively rare Haemophilia B.

The sex-linked X chromosome disorder manifests almost entirely in males, although the gene for the disorder is located on the X chromosome and may be inherited from either mother or father. Expression of the disorder is much more common in males than in females. This is because, although the trait is recessive, males only inherit one X chromosome, from their mothers. Thus if the hemophilia gene is transmitted on it, there is no possibility for the male to inherit a hemophilia-free gene from his father to mask or dilute the symptoms. By contrast, a female who inherits a gene for hemophilia on one of her X chromosomes will also have inherited a second X chromosome from the other parent which is likely to carry a hemophilia-free gene that would prevent full expression of symptoms.

Females who inherit the gene for Hemophilia A or B from both parents would be expected to manifest full symptoms, similar to those seen in affected males, but this is extremely rare. Despite frequent inter-marriage among royalty, no case of such double inheritance is known among Queen Victoria's descendants. However, it is possible that such cases have gone undocumented because of the potentially higher mortality affected females would likely experience, especially upon onset of menarche.

Although an individual's hemophilia can usually be traced in the ancestry, in about 30% of cases there is no family history of the disorder and the condition is speculated to be the result of spontaneous mutation in an ancestor.

Victoria appears to have been a spontaneous or de novo mutation and is usually considered the source of the disease in modern cases of hemophilia among royalty. Queen Victoria's father, Prince Edward, Duke of Kent, was not a hemophiliac, and the probability of her mother having had a lover who suffered from hemophilia is minuscule given the low life expectancy of 19th century hemophiliacs. Her mother, Victoria, Duchess of Kent, was not known to have a family history of the disease, although it is possible that the mutation began at her conception and was passed down only to Victoria and not to her other children. In the same way, had Queen Victoria herself only had seven children, the mutation would likely be assumed today to have occurred at the conception of Princess Alice, as she was the only known carrier among Victoria and Albert's first seven children.

Queen Victoria's eldest daughter, Victoria, apparently escaped the hemophilia gene as it did not appear in any of her descendants. Victoria's fifth child, Helena, may or may not have been a carrier; two healthy sons survived to adulthood but two other sons died in infancy and her two daughters did not have issue. Victoria's sixth child, Louise, died without issue. Her sons King Edward VII, Alfred, and Arthur were not hemophiliacs. However, her son Leopold was a sufferer of hemophilia and her daughters Alice and Beatrice were confirmed carriers of the gene.

Princess Alice

Alice, Victoria's third child, passed it on to at least three of her children: Friedrich, Irene, and Alix.

• Prince Friedrich of Hesse and by Rhine (known in the family as "Frittie"). Died before his third birthday of bleeding on the brain resulting from a fall from a third-storey window (which would almost certainly have been fatal even if he had not had hemophilia).

• Princess Irene of Hesse and by Rhine (later Princess Heinrich of Prussia), passed it on to two of her three sons:
  • Prince Waldemar of Prussia. Survived to age 56; had no issue.
  • Prince Heinrich of Prussia. Died at age 4.

• Princess Alix of Hesse and by Rhine. Alix had a marriage proposal from Prince Albert Victor, eldest son of the future King Edward VII; had she accepted, hemophilia could have returned to the direct line of succession in Britain. Instead she married Tsar Nicholas II of Russia and passed it on to her only son:
  • Tsarevitch Alexei. Murdered by the Bolsheviks at the age of 13, along with his parents and all four of his sisters. Alexei's hemophilia was one of the factors contributing to the collapse of Imperial Russia during the Russian Revolution of 1917. DNA testing of the Romanov family remains in 2009 showed that one of the four daughters, thought to be Maria by American researchers and Anastasia by Russian researchers, was a carrier. Grand Duchess Maria was thought by some to have been a symptomatic carrier because she haemorrhaged during a tonsillectomy.

• Princess Victoria of Hesse and by Rhine (later Victoria, Marchioness of Milford Haven), Alice's oldest child and maternal grandmother to Prince Philip, Duke of Edinburgh, might have inherited the mutation, though the gene remained hidden for several generations before possibly reappearing in the descendants of her eldest granddaughter, Princess Margarita of Greece and Denmark (see below).

• Princess Elizabeth of Hesse and by Rhine (later Grand Duchess Elizabeth Feodorovna of Russia), may or may not have been a carrier. She was childless when killed by the Bolsheviks in 1918.

• Princess Marie of Hesse and by Rhine, Alice's seventh and last child, may or may not have been a carrier. She died of diphtheria at the age of four.

Prince Leopold

Leopold, Victoria's eighth child, was a hemophiliac who died from bleeding after a fall. He lived to the age of 30, long enough to pass the gene on to his only daughter (his posthumous son being unaffected, as is usual when the gene is carried only by the father):

• Princess Alice of Albany (later Countess of Athlone), who in turn passed it on to her oldest son:
  • Prince Rupert of Teck (died at the age of 20, bleeding to death after a car accident)

Alice of Albany's youngest son Prince Maurice of Teck, died in infancy, so it is not known if he was a sufferer. Her daughter Lady May Abel Smith, Leopold's granddaughter, has living descendants none of whom has been known to have or to transmit hemophilia.

Princess Beatrice

Princess Beatrice (later Princess Henry of Battenberg), Victoria's ninth and last child, passed it on to at least two, if not three, of her four children:

• Princess Victoria Eugenie of Battenberg (later Queen Victoria Eugenia of Spain), who passed it on to
  • Infante Alfonso of Spain, Prince of Asturias. Died at age 31, bleeding to death after a car accident.
  • Infante Gonzalo. Died at age 19, bleeding to death after a car accident.
  • Victoria Eugenie's two daughters, Infantas Beatriz and Maria Cristina of Spain, both have living descendants none of whom has been known to have or to transmit hemophilia.
• Prince Leopold of Battenberg (later, Lord Leopold Mountbatten). Died at age 32 during a knee operation.
• Prince Maurice of Battenberg. Killed in action in World War I in 1914 at the age of 23. Maurice's hemophilia is disputed by various sources: It seems unlikely that a known hemophiliac would be allowed to serve in combat.

Today

No living member of the present or past reigning dynasties of Europe is known to have symptoms of hemophilia or is believed to carry the gene for it. The last descendant of Victoria known to suffer from the disease was Infante Don Gonzalo, born in 1914, although dozens of descendants of Queen Victoria's (including males descended only through females) have been born since 1914. However, because the hemophilia gene usually remains hidden in females who only inherit the gene from one parent, and female descendants of Victoria have left many descendants in royal and noble families, there remains a small chance that the disease could appear again, especially among the female-line Spanish descendants of Princess Beatrice.

• Infanta Beatríz's two sons were not affected by the disease. Beatriz's eldest daughter, Sandra, has two children, a son and daughter. Her son is not affected, and her daughter has two sons, who are apparently unaffected. Beatríz's youngest daughter, Olimpia, had six children; her two eldest daughters, Beatrice and Sibilla are both married with children, none of whom, in the case of their sons, appear to be hemophiliacs. If Sibilla's descendants were to express or transmit the gene, however, another reigning dynasty of Europe would, in the 21st century, join the rest of the reigning families that inherited the disease from Queen Victoria. Olimpia's youngest daughters are still unmarried, but there is still a chance they could be carriers. Another daughter, Laura, died as a child, as did her only son, Paul, the latter of whom was apparently not a hemophiliac.
• Infanta Maria Cristina had four daughters, all potential carriers. Her eldest daughter, Vittoria Eugenie, had a daughter and three sons, the latter all apparently unaffected. The Infanta's second daughter, Giovanna, had only one child, an unaffected son. Her two youngest daughters, Donna Maria Teresa and Donna Anna Sandra, also have only daughters. Of these, only one, Maria Teresa's second daughter, Isabel, is married, but she also has only a daughter. There is a chance the disease may remain in this branch of Princess Beatrice's descendants.

Ferdinand Soltmann

At least one modern descendant of Queen Victoria has been diagnosed with hemophilia: Ferdinand Soltmann, the son of Princess Xenia of Hohenlohe-Langenberg, born 2005. Xenia is a male-line descendant of Victoria, but the disease did not come from Xenia's maternal family, the Croÿs. If the disease came from Xenia, there are two possibilities. The first possibility is that it would have had to be inherited from her father, Kraft, Prince of Hohenlohe-Langenberg, a descendant of Victoria through the female line. Kraft had some clotting issues, which led the family to believe he may have been a mild hemophiliac. If Kraft was a hemophiliac, then his daughters Xenia and Cécile were definitely carriers. The second possibility is that Xenia or Ferdinand had a spontaneous mutation, as Victoria herself apparently had.

Xenia is descended from Victoria in two different lines, through Victoria's children Princess Alice of the United Kingdom and Alfred, Duke of Saxe-Coburg and Gotha. Alfred was not a hemophiliac, but Alice was a carrier, and her line of descent to Xenia, and subsequently, Ferdinand, is as follows.

Queen Victoria

Princess Alice of the United Kingdom

Princess Victoria of Hesse and by Rhine

Princess Alice of Battenberg

Princess Margarita of Greece and Denmark

Kraft, 9th Prince of Hohenlohe-Langenburg

Princess Xenia of Hohenlohe-Langenburg

Ferdinand Soltmann

Chronological order

Queen Victoria died in 1901 so she lived to see a son and, possibly, a grandson die from the disease. A great-grandson was diagnosed with the disease as well. There is no sign of the disease into later generations, but it has been known to skip several generations.

Men who died of Haemophilia in Order of Death

#	Name	Death	Relation to Queen Victoria
1	Prince Friedrich of Hesse and by Rhine	29-May-1873	grandson
2	The Prince Leopold, Duke of Albany	28-Mar-1884	son
3	Prince Heinrich Friedrich of Prussia	26-Feb-1904	great grandson
4	Prince Maurice of Battenberg (disease unconfirmed)	27-Oct-1914	grandson
5	Lord Leopold Mountbatten	23-Apr-1922	grandson
6	Prince Rupert of Teck	15-Apr-1928	great grandson
7	Infante Gonzalo of Spain	13-Aug-1934	great grandson
8	Alfonso, Prince of Asturias	6-Sep-1938	great grandson
9	Prince Waldemar of Prussia	2-May-1945	great grandson

Type of hemophilia discovered

Because the last known descendent with hemophilia of Queen Victoria's family tree died in the 1940s, the exact type of hemophilia found in this family remained unknown until 2009. Using genetic analysis of the remains of the assassinated Romanov dynasty, and specifically Tsarevich Alexei, Rogaev et al. were able to determine that the "Royal Disease" is actually hemophilia B.

References and external links

• Potts, D. M. Queen Victoria's Gene. Sutton Publishing, 1999. ISBN 0-7509-1199-9.
• "Hemophilia: The Royal Disease"
• Family tree of Queen Victoria and her descendants
• Another family tree