Haemophilia in European royalty

From Wikipedia, the free encyclopedia
Jump to: navigation, search

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, haemophilia was once popularly called "the royal disease". Tests of the remains of the Romanov imperial family show that the specific form of haemophilia passed down by Queen Victoria was probably the relatively rare Haemophilia B.[1]

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 haemophilia gene is transmitted on it, there is no possibility for the male to inherit a haemophilia-free gene from his father to mask or dilute the symptoms. By contrast, a female who inherits a gene for haemophilia on one of her X chromosomes will also have inherited a second X chromosome from the other parent which is likely to carry a haemophilia-free gene that would prevent full expression of symptoms.

Females who inherit the gene for Haemophilia 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.

Although an individual's haemophilia 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.[2]

Victoria appears to have been a spontaneous or de novo mutation and is usually considered the source of the disease in modern cases of haemophilia among royalty. Queen Victoria's father, Prince Edward, Duke of Kent, was not a haemophiliac, and the probability of her mother having had a lover who suffered from haemophilia is minuscule given the low life expectancy of 19th-century haemophiliacs. 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 probably 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, Princess Royal, apparently escaped the haemophilia gene as it did not appear in any of her matrilineal 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 haemophiliacs. However, her son Leopold was a sufferer of haemophilia and her daughters Alice and Beatrice were confirmed carriers of the gene.

Queen Victoria family tree[edit]

Princess Alice[edit]

Alice (1843-1878), Victoria's third child, and wife of the future Grand Duke Louis IV of Hesse and by Rhine (1837-1892), passed it on to at least three of her children: Irene, Friedrich, and Alix.

Prince Leopold[edit]

Leopold (1853-1884), Victoria's eighth child, was the first member of the family to manifest haemophilia; he died at age 30 from bleeding after a minor fall,[5] only two years after marrying Princess Helena of Waldeck and Pyrmont. (1861-1922)

He passed the gene on to his only daughter, as all of the daughters of a haemophiliac father would inherit the gene:

Alice'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 (1906-1994), Leopold's granddaughter, has living descendants none of whom has been known to have or to transmit haemophilia.

Leopold's posthumous son, Charles Edward (1884-1954), was unaffected, as fathers cannot pass the gene to a son.

Princess Beatrice[edit]

Princess Beatrice (1857-1944), Victoria's ninth and last child, and wife of Prince Henry of Battenberg (1858-1896) passed it on to at least two, if not three, of her four children:

Today[edit]

No living member of the present or past reigning dynasties of Europe is known to have symptoms of haemophilia 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 haemophilia 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 haemophiliacs. 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 haemophiliac.[citation needed]
  • 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.

Chronological order[edit]

Queen Victoria died in 1901 so she lived to see her youngest son and a grandson die from the disease. A great-grandson was diagnosed with the disease as well. The gene can be passed down the female line without a haemophiliac son being born, but as the family line continues and no haemophiliac sons are born, it becomes more and more statistically unlikely that a certain ancestor had the gene and passed it on through the female line.

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 Lord Leopold Mountbatten 23-Apr-1922 grandson
5 Prince Rupert of Teck 15-Apr-1928 great grandson
6 Infante Gonzalo of Spain 13-Aug-1934 great grandson
7 Alfonso, Prince of Asturias 6-Sep-1938 great grandson
8 Prince Waldemar of Prussia 2-May-1945 great grandson

Type of haemophilia discovered[edit]

Because the last known descendant of Queen Victoria with haemophilia died in the 1940s, the exact type of haemophilia 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 haemophilia B. Specifically, they found a single-nucleotide change in the gene for clotting Factor IX that causes incorrect RNA splicing and produces a truncated, nonfunctional protein.[6]

Notes[edit]

  1. ^ a b "Case Closed: Famous Royals Suffered from Hemophilia". Michael Price, ScienceNOW, October 9, 2009.
  2. ^ "Hemophilia B". Retrieved 2007-11-21. 
  3. ^ Ian Vorres, The Last Grand Duchess, 1965 p. 115.
  4. ^ Massey, Nicholas and Alexandra, 1967
  5. ^ Aronova-Tiuntseva, Yelena; Clyde Freeman Herreid (2003). "Hemophilia: "The Royal Disease"". Science Cases: 1–7. Retrieved 23 March 2013. 
  6. ^ Rogaev EI, Grigorenko AP, Faskhutdinova G, Kittler EL, Moliaka YK (November 2009). "Genotype analysis identifies the cause of the "royal disease"". Science 326 (5954): 817. doi:10.1126/science.1180660. PMID 19815722. 

References and external links[edit]