The Habsburg dynasty, which ruled Spain during the height of its power and influence, may have been brought down by genetic disorders caused by inbreeding, according to a new study.
The 174-year dynasty was replaced by the French Bourbons in 1700 when King Charles II died at the age of 39 without offspring.
Spanish researchers computed "the inbreeding coefficient" of the Habsburg kings to conclude that "a high incidence consanguineous marriages", or those between two close relatives, may have caused genetic disorders in Charles II.
Charles was physically and mentally disabled and disfigured, the researchers noted in their study, published in the US Public Library of Science journal PLoS ONE.
According to contemporary writings, he was unable to speak until the age of four, could not walk until the age of eight, and during the last years of his life he barely could stand up and suffered from hallucinations and convulsive episodes, it said.
"It is speculated that the simultaneous occurrence in Charles II of two different genetic disorders: combined pituitary hormone deficiency and distal renal tubular acidosis ... could explain most of the complex clinical profile of this king, including his impotence/infertility which in last instance led to the extinction of the dynasty."
It said that in a bid to maintain the dynasty, the Habsburg kings had "frequently married close relatives in such a way that uncle-niece, first cousins and other consanguineous unions were prevalent."
In total, nine of 11 marriages were "consanguineous unions in a degree of third cousins or closer."
The inbreeding coefficient increased strongly along the Habsburg generations, said the study by researchers at the University of Santiago de Compostela and the Galician Public Foundation for Genomic Medicine.
It noted a coefficent of 0.025 for King Philip I, the founder of the dynasty and who married his niece, Anne of Austria, to 0.254 for Charles II, and said several members of the dynasty had coefficients higher than 0.20.
In addition, it pointed to other evidence that infant and child mortality was very high among the Spanish Habsburgs, far higher that the rates registered for Spanish villages at the time.
"These data suggest that inbreeding depression for infant and child survival could be occurring in the Spanish Habsburg families as a consequence of prolonged consanguineous marriages."
During the Habsburg dynasty, Spain's worldwide empire reached its apogee, controlling territories in the Americas and the Philippines and parts of western Europe.
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