On November 6, 1650, William II, the Prince of Orange, stadtholder of the Netherlands died, leaving his widow, Mary, the former Princess Royal of England (daughter of Charles I and Henrietta Maria) as the regent for their son William III, Prince of Orange, who was born posthumously. The Prince of Orange was only 24 years old and died of smallpox. His widow would survive him until December 24, 1660, when she was only 29 years old, also of smallpox.
Their son would marry another royal princess, also named Mary (James, the Duke of York's daughter) and William and Mary would reign together as King and Queen of England after the Glorious Revolution, until Mary's death in 1694--of smallpox.
William III died of not smallpox but pneumonia in 1702.