Haemophilia and the Haemophilia and the royal families of Europeroyal families of Europe

What is haemophiliaWhat is haemophilia

It is an X-linked genetic disease, hence the genetic It is an X-linked genetic disease, hence the genetic abnormality is found on the X chromosome.abnormality is found on the X chromosome.

There are two types heamophilia A and There are two types heamophilia A and B.Haemophilia A has a deficit in factor viii and B in B.Haemophilia A has a deficit in factor viii and B in factor ixfactor ix

It usually presents in infancy with recurrent It usually presents in infancy with recurrent bleeds, ,painful haemarthoses and haematomas and bleeds, ,painful haemarthoses and haematomas and intracranial hemorrhagesintracranial hemorrhages

Bleeding episodes are treated with Factor viii or ix Bleeding episodes are treated with Factor viii or ix replacement. DDAVP is also usedreplacement. DDAVP is also used

InheritanceInheritance The Earliest written recognition of hemophilia was in The Earliest written recognition of hemophilia was in

2nd century AD in Jewish writings2nd century AD in Jewish writings Females are usually carriers, Since they have a Females are usually carriers, Since they have a

chromosomal make-up of XX, inheriting an X chromosomal make-up of XX, inheriting an X chromosome with disease mutations will generally chromosome with disease mutations will generally not produce the disease condition asnot produce the disease condition as the other normal the other normal X chromosome can compensate.X chromosome can compensate.

Hemophilia affects males much more frequently (1 in Hemophilia affects males much more frequently (1 in 10,000) than females (1 in 100,000,000). 10,000) than females (1 in 100,000,000).

Spontaneous mutation can occur . In 33% of patients Spontaneous mutation can occur . In 33% of patients there is no family history of haemophiliathere is no family history of haemophilia

““The royal disease”The royal disease”

haemophilia became known as the haemophilia became known as the

““Royal disease” because it spread Royal disease” because it spread

to the royal families of Europe through to the royal families of Europe through Victoria’s descendantsVictoria’s descendants

Haemophilia appeared in Queen Victoria’s Haemophilia appeared in Queen Victoria’s children, and through them spread into the children, and through them spread into the royal families of Europeroyal families of Europe

Queen Victoria family treeQueen Victoria family tree

Queen Victoria had 9 children. One Queen Victoria had 9 children. One hemophilic son and two daughters that hemophilic son and two daughters that were carrierswere carriers

Queen Victoria had no ancestors with the Queen Victoria had no ancestors with the condition but soon after the birth of her condition but soon after the birth of her eighth child, Leopold, in 1853 it became eighth child, Leopold, in 1853 it became evident that he had haemophiliaevident that he had haemophilia ( (the son the son Leopold died at the age of 31, from a intra Leopold died at the age of 31, from a intra cerebral haemorrhage and was described as cerebral haemorrhage and was described as “very delicate”“very delicate”))

With the appearance of hemophilia in the With the appearance of hemophilia in the royal family the Queen could only protest royal family the Queen could only protest that the disease did not originate in her side that the disease did not originate in her side of the family.and they often blamed the of the family.and they often blamed the “curse of the Coburgs”“curse of the Coburgs”..

How did the gene get introduced into How did the gene get introduced into the royal familythe royal family

There were several suggestions how the There were several suggestions how the haemophilic gene entered the royal familyhaemophilic gene entered the royal family

1 .spontaneous mutation1 .spontaneous mutation 2.and the most controversial : that queen Victoria 2.and the most controversial : that queen Victoria

wasn’t the Duke of Kent’s daughter.wasn’t the Duke of Kent’s daughter. The most accepted theory is that of spontaneous The most accepted theory is that of spontaneous

mutation ,as mutation ,as 30% of cases represents with new 30% of cases represents with new mutations, it is more likely that Victoria's carrier mutations, it is more likely that Victoria's carrier state was due to a new germ line mutation in her state was due to a new germ line mutation in her parents or grandparents parents or grandparents

The haemophilic gene has now died out in these The haemophilic gene has now died out in these Royal families, Thus we do not know to this day if Royal families, Thus we do not know to this day if the condition was haemophilia A or Bthe condition was haemophilia A or B

Affecting European royaltyAffecting European royalty Queen Victoria was known as a Queen Victoria was known as a

successful dynasty as her children successful dynasty as her children and grandchildren married widely and grandchildren married widely among the powerful ruling families among the powerful ruling families of Europe.of Europe.

Hence the haemophilic gene spread Hence the haemophilic gene spread through the royal houses of Europe through the royal houses of Europe as monarchs arranged marriages to as monarchs arranged marriages to consolidate political alliancesconsolidate political alliances . . Hence the Russian , Spanish and Hence the Russian , Spanish and German royal families were affected.German royal families were affected.( as two of the daughters of Queen ( as two of the daughters of Queen Victoria were carriers)Victoria were carriers)

The Russian connectionThe Russian connection

Alix of Hesse was one of Victoria’s grand daughters and Alix of Hesse was one of Victoria’s grand daughters and married Tsar Nicholas II of Russia, becoming Tsarina married Tsar Nicholas II of Russia, becoming Tsarina Alexandra.Alexandra.

she was a carrier and her fifth child and only son, Alexi, was she was a carrier and her fifth child and only son, Alexi, was born in 1904. He was a haemophiliac born in 1904. He was a haemophiliac

Alexi’s hemophilia discovered shortly after birth because of Alexi’s hemophilia discovered shortly after birth because of excessive bleeding from his umbilicus excessive bleeding from his umbilicus

RasputinRasputin Rasputin got involved with the Romanovs when Alexei

got a bruise after falling off a horse and the tsarina was looking everywhere for help. And Rasputin was suggested by her best friend as he was known to be a “charismatic peasant healer”.

He seemed to be the only one able to soothe AlexeiHe seemed to be the only one able to soothe Alexei It is still unsure how Rasputin was able to soothe the

child. It is believed that he hypnotised the boy. Rasputin was a very unpopular and controversial figure,

leading a scandalous personal life. His connection with the Romanovs stained the royal family

Rasputin was given much authority by Alexandra because Rasputin was given much authority by Alexandra because of his “healing powers”, and he was thus able to influence of his “healing powers”, and he was thus able to influence politics and decision makingpolitics and decision makingHe soon became her confidant and personal advisor. He also convinced her to fill some government offices with his own handpicked candidates

This reliance enhanced Rasputin's political power, which This reliance enhanced Rasputin's political power, which seriously undermined the Romanov rule during the First seriously undermined the Romanov rule during the First World War. World War.

The revolutionThe revolution At this point Russia was in turmoil Alexandra was unpopular in Russia during

the first world war, as her connection with the German royalty and she was thought to be a spy.

The Russian Revolution began in 1914. Tsar Nicholas II was not a strong leader, and his son’s illness only added to his inability to rule his country by making the family more sheltered and out of touch with the people

Nicholas II abdicated in 1917 The family was executed on July 17, 1918. Many historians attribute much of the Tsar’s Many historians attribute much of the Tsar’s

fall to his son’s illness and his inability to fall to his son’s illness and his inability to take more effective steps and there is little take more effective steps and there is little doubt of the influence of Rasputin.doubt of the influence of Rasputin.

The German connectionThe German connection

Queen Victoria’s grandQueen Victoria’s grand-daughter -daughter Irene of Irene of Hesse, Princess of PrussiaHesse, Princess of Prussia introduced the introduced the gene into the German imperial familiesgene into the German imperial families

She had three sons, two of whom were haemophiliacs

Spanish royal familySpanish royal family

Princess Victoria Eugenie Battenberg of Princess Victoria Eugenie Battenberg of England , Queen Victoria's grand daughter England , Queen Victoria's grand daughter married King Alfonso XIII of Spain married King Alfonso XIII of Spain

She gave birth to 7 children , 2 haemophilic She gave birth to 7 children , 2 haemophilic sons and only one healthy son.sons and only one healthy son.

2 sons had haemophilia, one son was stillborn, the second 2 sons had haemophilia, one son was stillborn, the second eldest son was death and muteeldest son was death and mute

This news of haemophilia damaged Victoria Eugenia's relation This news of haemophilia damaged Victoria Eugenia's relation with her husband. It also sent the King into a tailspin of with her husband. It also sent the King into a tailspin of irresponsible behaviour that led him to abandon the affairs of irresponsible behaviour that led him to abandon the affairs of daily government to questionable characters and dictators .daily government to questionable characters and dictators .

this also weakened the position of monarchy in Spain and this also weakened the position of monarchy in Spain and discredited the heirs and may have lead to the civil war.discredited the heirs and may have lead to the civil war.

It is impossible to measure exactly the effect of these tragedies It is impossible to measure exactly the effect of these tragedies on the Spanish throne.The Spanish society was so deeply on the Spanish throne.The Spanish society was so deeply divided and flawed that civil war might have been divided and flawed that civil war might have been unavoidable, but undoubtedly helped to weaken the position of unavoidable, but undoubtedly helped to weaken the position of the throne.the throne.