The following is from Neatorama via the Holy Whapping:

The 1515 Flemish painting, by an unknown artist, . . . shows an angel (next to Mary) and possibly one other figure, the shepherd in the centre of the background with the syndrome.

“If our diagnosis is correct, this implies that Down’s syndrome is not a modern disease,” say [Levitas and Reid] (American Journal of Medical Genetics 2003;116:399-405).

The diagnosis of Down’s syndrome in the angel was based on a number of features: a flattened mid-face, epicanthal folds, upslanted palpebral fissures, a small and upturned tip of the nose, and downward curving of the corners of the mouth. The hands, crossed over the breast, have short fingers, especially on the left.

Hat tip to Drew and the Shrine of the Holy Whapping.