Seventeenth-century European noble culture commonly matched cousin to first cousin and uncle to niece, to preserve a prosperous family's properties. Charles's own immediate pedigree was exceptionally populated with nieces giving birth to children of their uncles: Charles's mother was niece of Charles's father, being daughter of Maria Anna of Spain (1606–46) and Emperor Ferdinand III. Thus, Empress Maria Anna was simultaneously his aunt and grandmother.[1] This inbreeding had given many in the family hereditary weaknesses. That Habsburg generation was more prone to still-births than were peasants in Spanish villages.[2]
There was also insanity in Charles's family; his great-great-great(-great-great, depending along which lineage one counts) grandmother, Joanna of Castile ("Joanna the Mad"), mother of the Spanish King Charles I (who was also Holy Roman Emperor Charles V) became insane early in life. Joanna was two of Charles' 16 great-great-great-great-grandmothers, six of his 32 great-great-great-great-great-grandmothers, and six of his 64 great-great-great-great-great-great-grandmothers.
Dating to approximately the year 1550, outbreeding in Charles II's lineage had ceased. From then on, all his ancestors were in one way or another descendants of Joanna the Mad and Philip I of Castile, and among these just the royal houses of Spain, Austria, and Bavaria. Charles II's genome was more homozygous than in an average brother-sister offspring.[2] He was born physically and mentally disabled, and disfigured. Possibly through affliction with mandibular prognathism, he was unable to chew. His tongue was so large that his speech could barely be understood, and he frequently drooled. It has been suggested that he suffered from the endocrine disease acromegaly,[3] or his inbred lineage may have led to a combination of rare genetic disorders such as combined pituitary hormone deficiency and distal renal tubular acidosis.[2]
Consequently, Charles II is known in Spanish history as El Hechizado ("The Hexed") from the popular belief – to which Charles himself subscribed – that his physical and mental disabilities were caused by "sorcery." The king went so far as to be exorcised.