Young: Medical Genetics 
Multiple Choice QuestionsYoung: Medical Genetics
Chapter 12
Queen Victoria (1819-1901)
Photo of Queen Victoria at the time of her Golden Jubilee (1887)
Queen Victoria, the grand-daughter of George the Third (p. 218), reigned as British sovereign from 1837 until her death at the age of 81 years in 1901. Her monarchy was associated with a period of unparalleled prosperity for Britain as the industrial revolution heralded the establishment of a Commonwealth which straddled the entire globe.
Although she herself enjoyed good general health, her genetic legacy proved to be disastrous for several of the royal houses of Europe (Fig 1). Victoria had a total of nine children, four sons and five daughters. One of her sons, Leopold, was affected with haemophilia and died at the age of 31 years as a result of a cerebral haemorrhage following a fall. Leopold, through his daughter Alice, had an affected grandson, Rupert, who died at age 20 years. Of much greater importance for European politics, two of Victoria’s daughters, Alice and Beatrice, proved to be carriers of haemophilia. Alice married the Duke of Hesse (in Germany) and had one affected son, Frederick, and two carrier daughters, Irene and Alix. Irene married into the Prussian royal family and had two affected sons, Waldemar and Heinreich. Alix married the Russian Czar, Nicholas II, with whom she had four daughters and a single son, Alexis. Alexis proved to be affected and his severe bleeding prompted his mother to seek help from unconventional sources, most notably, and with tragic consequences, the ‘mad monk’ Rasputin, whose influence with the Czar’s wife contributed to the royal family’s decreasing popularity and eventual mass murder at Ekaterinberg in 1917.
Meanwhile Beatrice’s carrier status proved to have equally tragic and devastating consequences for the Spanish royal family. As well as having two affected sons, Leopold and Maurice, she had a daughter, Eugenie, who married King Alfonso of Spain and in turn had two affected sons, the older of whom, also called Alfonso, was the heir to the doomed Spanish throne.
Figure 1 Modified version of Queen Victoria’s family tree showing haemophilia amongst her descendants.
Thus, in the space of three short generations Queen Victoria through her daughters had unwittingly transmitted a potentially fatal disorder to three of the most powerful royal families of Europe, thereby almost certainly contributing to their ultimate downfall.
It is not known whether Queen Victoria was a carrier of haemophilia A or B, which are caused by deficiency of clotting Factors VIII and IX respectively. Both play a critical role in the intrinsic pathway activation of prothrombin to thrombin, which then converts fibrinogen to fibrin to form the structural framework of clotted blood. Both conditions can now be treated very successfully using replacement recombinant therapy as described on page 231.
Nor is it known whether Victoria’s mother was a carrier or whether Victoria acquired her carrier status as a result of inheriting a new mutation from one of her parents. None of her antecedents is known to have been affected, so that it is likely that her carrier status resulted from a new mutation occurring in one of the gametes which led to her conception. In keeping with this observation is the fact that her father, Edward Duke of Kent, was born in 1767, so that he would have been aged over 50 years at the time of her conception. This would be consistent with the well documented association of advanced paternal age with new mutations resulting from copy errors in DNA replication, as explained on page 37. It is now also known that the male to female ratio for new point mutations in gametogenesis in both haemophilia A and B is approximately 10 to 1.
Click on the image below to see a family tree of British monarchs from Queen Victoria to the present day 
Family tree drawn by Muriel Gottrop (November 2004)
References
Mannucci PM, Tuddenham EGD (2001) The hemophilias – from royal genes to gene therapy. New England Journal of Medicine, 344, 1773-1779.
Potts M, Potts W (1995) Queen Victoria’s gene. Alan Sutton, Stroud, UK.
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