This is more of a hypothesis than a fact, but there are credible claims that Henry VIII suffered from the so-called McLeod syndrome and the associated Kell-positive blood type, which is a rare recessive genetic variant affecting the X gene and which he may have inherited from his maternal great grandmother (Jaquetta of Luxemburg) who may have carried this gene. The syndrome would explain both the high mortality among the second-born children that Henry VIII had with his many wives (and similar issues of other male relatives of Jaquetta) and whose pregnancies often ended in miscarriage and (male) children who did not survive infancy, as well as Henry VIII’s early mental decline.

Perhaps not really mind blowing, but I think it’s crazy that the historical events of that time and the “Elizabethan era” that followed might have been shaped in this way by a single occurrence of a specific genetic disorder.