The first recorded heterozygote for familial hypercholesterolemia

Abstract

In a recent review, Ose cites the Madonna Lisa Maria de Gherardini (1479–1506), the subject of Leonardo da Vinci’s painting, Mona Lisa, as the first recorded case of heterozygous familial hypercholesterolemia (HeFH). This opinion is based on what appears to be a xanthelasma in the inner canthus of her left orbit and a swelling just behind the metacarpophalangeal joint of her left hand. The swelling is not definitely a tendon xanthoma, although a gouty tophus, which it might also resemble, would be unlikely in a women of her age unless she had chronic renal disease. The xanthelasma looks more convincing, but could be an epidermal cyst. Indisputable xanthelasmata did not appear in any medical text until Rayer’s Atlas of Skin Disorders (1835). His illustration is labelled ‘‘Plaques jaunes disposes d’une maniere, symmetrique sur les paupieres des deux yeux.’’ Addison and Gull were next to describe xanthelasmata, which they termed ‘‘vitiligoidea plana’’ in 1851. At lease three of their cases had the dyslipidemia of chronic obstructive jaundice and another had what we would currently regard as dysbetalipoproteinemia. Tendon xanthomata, the characteristic feature of HeFH, were believed to have first been recorded by Frans Hals in his ‘‘Portrait of an Elderly Lady’’ painted in 1633. The dorsa of her hands undoubtedly show tendon xanthomata. The fact that she reached old age is quite compatible with the evidence that HeFH was not associated with early cardiovascular death in The Netherlands until around the turn of the 19th century. The first medical descriptions of tendon xanthomata as a feature of HeFH were made in the 20th