[Charles II: From spell to genitourinary pathology]

Area of Science:

• Medical history
• Genetics
• Endocrinology

Background:

• Charles II of Spain, the last Hapsburg monarch, suffered from a debilitating genitourinary disorder that prevented him from producing an heir.
• His condition was exacerbated by a history of consanguineous marriages within the Hapsburg dynasty, leading to widespread speculation and the belief he was 'bewitched'.

Discussion:

• Analysis suggests Charles II may have had posterior hypospadias, monorchism, and an atrophic testicle, contributing to an intersex state with ambiguous genitalia.
• His phenotype aligns more with true hermaphroditism or XX male syndrome, possibly with Fragile X syndrome, rather than Klinefelter's syndrome.
• Congenital monorenal condition and chronic kidney failure due to nephropathy and recurrent urinary tract infections likely caused his death.

Key Insights:

• The Hapsburg dynasty's end in Spain was precipitated by Charles II's complex pluripathological condition.
• Endogamic matrimonial policies significantly contributed to the Habsburg dynasty's extinction.
• Genetic and chromosomal analysis of Charles II's remains is crucial for definitive diagnosis.

Outlook:

• Further research into Charles II's genetic makeup could provide definitive answers regarding his intersex condition.
• Understanding the genetic impact of royal inbreeding offers insights into historical health outcomes.
• The case of Charles II highlights the long-term consequences of consanguinity on dynastic survival.