Abstract
Nearly 100 years ago, on September 20, 1887, a 24-year-old woman was admitted to William Osier's service at the Philadelphia Infirmary for Nervous Diseases with chronic intermittent "attacks of transient swelling in various parts — hands or fingers, knee caps, elbows, buttocks, arm or thigh in fleshy parts, face, or more often the lips alone."1 Osier declined to speculate about mechanisms, but he did identify a genetic basis for the edema. From the patient's 92-year-old grandfather, Osier obtained a remarkable history of similar episodes in five generations of the family, beginning with the patient's great-grandmother, Margaret A, born in 1762. . . .