The enigma of Henry IV's disease: Did he suffer from McCune-Albright syndrome/fibrous dysplasia?

• Published in: Revista española de patología Vol. 56; no. 4; pp. 243 - 251
• Main Authors: Tuñón Álvarez, M Teresa, Ruiz Calleja, Adolfo, Pérez de Nanclares, Guiomar
• Format: Journal Article
• Language: Spanish
• Published: Spain 01.10.2023
• Subjects: Acromegaly - complications; Acromegaly - genetics; Adenoma; Chromogranins; Fibrous Dysplasia, Polyostotic - complications; Fibrous Dysplasia, Polyostotic - diagnosis; Fibrous Dysplasia, Polyostotic - genetics; Humans; Male; Syndrome; Enrique IV; Fibrous dysplasia; McCune-Albright; GNAS; Henry IV; Trastámara; Displasia fibrosa
• ISSN: 1988-561X
• DOI: 10.1016/j.patol.2023.06.003

Henry IV King of Castile, last king of the Trastámara dynasty, was the brother of Isabella the Catholic. He is known as "the impotent". Based on previous descriptions by historians and biographers, Gregorio Marañón in 1922 described him as "eunuchoid dysplastic with acromegalic reaction and clear schizoid features". In 1946, a post-mortem inspection was carried out on the mummified corpse found in the Monastery of Guadalupe. A written document and some photographs were recorded. We have collected the signs and symptoms described and applied the international classification of diseases recommended by the World Health Organisation, ICD11-2023. We have relied on the coins issued in the money of Henry IV, on which we have identified enlargement of the thyroid gland. With the data available at this time, we suggest that Henry IV most probably suffered from: facial and polyostotic bone dysplasia, kyphosis, limb limping, multiple endocrine disorders, acromegaly with macrognatia, nodular thyroid disease, malodorous diaphoresis, erectile dysfunction, hypospadias, abnormal sexual development, "feminoid pelvis", abdominal colic, oligodontia and dental displacement. It is possible that he also suffered from: precocious puberty, renal lithiasis with debilitating phosphaturia, carpal tunnel, thrombopenia and growth hormone-producing pituitary hyperplasia or adenoma. We suggest that Henry IV may have suffered from McCune-Albrigth syndrome associated with fibrous dysplasia, a rare disease due to gain-of-function mutations in the GNAS gene.