Is Down Syndrome A Modern Disease?

IS DOWN SYNDROME A MODERN DISEASE? E. PETER VOLPE* Down syndrome is the most common congenital disorder associated with severe mental retardation. The clinical features of this syndrome are quite distinctive and readily discernible to the untrained eye. The congenital disability is unmistakably stamped on the affected child's face: a prominent forehead, a flattened nasal bridge, a habitually open mouth, a projecting lower lip, a protruding tongue, slanting eyes, and a perceptible fold of lax skin (epicanthic fold) at the inner corner of each eye. This unique syndrome was the first human developmental anomaly to be traced to an alteration in the chromosome complement—namely, trisomy of chromosome 21 or, simply, trisomy 21. Down syndrome occurs about once in every 700 births, which means that of the approximately 10,000 births each day in the United States, 14 newborn infants are likely to be afflicted with this disability. The number of affected newborns would be higher were it not for the fact that four out of five conceptuses with trisomy 21 terminate in spontaneous abortion. This signifies great pregnancy wastage or, stated differently, strong natural selection against this particular type of chromosomally abnormal fetus. Down syndrome is so common and so apparent clinically that it is surprising, if not startling, that the condition was recognized as a distinct entity only slightly more than a century ago. The first comprehensive description of this disability was provided by John Langdon Down in a short paper published in the London Hospital Reports in 1866 [I]. Langdon Down (fig. 1) was then medical superintendent of the Earlswood Asylum for Idiots in Surrey, England, a position he held for about a decade. After leaving Earlswood, he established his own private home The author is indebted to Wilma Parrish for her tireless efforts in researching the art archives, as well as for her constructive criticism and encouragement in the preparation of this paper. The author is also indebted to Charles Hockman, George Bernard, and Lucy Andrews for their critical reading of the manuscript. *Professor of human genetics, School of Medicine, Mercer University, Macon, Georgia 31207.© 1986 by The University of Chicago. All rights reserved. 003 1-5982/86/2903-0491$01 .00 Perspectives in Biology and Medicine, 29, 3, Part 1 ¦ Spring 1986 \ 423 Fig. 1.—John Langdon Down, the London physician who in 1866 provided the first comprehensive description of the congenital disorder that now bears his name. (Courtesy of The Royal Society of Medicine.) for mentally retarded youngsters at a period in history when community interest in organizing schools for the mentally deficient finally wakened. Ironically, the disorder might not have been identified as a discrete entity had it not been for Down's unconventional approach to classifying congenital mental defects according to ethnic similarities. Langdon Down seized upon the Oriental-like slant of the eye to designate the condition as a "Mongolian type of idiocy." Notwithstanding his excursion into quasi anthropology, Langdon Down prepared a keen description of the disorder that now bears his name. I As seems to happen quite often in science, Langdon Down's article lay ignored or unappreciated until another report on the same subject appeared 10 years later. In the July 1876 issue of the Journal of Mental Science [2], John Fraser and Arthur Mitchell described the distinguishing physical characters of an apparently new class of idiots. Although these authors ostensibly were unaware of Langdon Down's paper, they too called attention to the Oriental-like appearance of the patients and pro424 I E. Peter Volpe ¦ Down Syndrome , Fig. 2.—The first pictorial illustration in the medical literature of a person affected with Down syndrome, as depicted in an article by Fraser and Mitchell in 1876 [2]. posed to describe the condition as "Kalmuc idiocy." Physically of small stature, the Kalmucks (or Kalmyks) are Mongolians who migrated to the lower Volga region of Russia. The patients described by Fraser and Mitchell clearly matched the account presented earlier by Langdon Down. The authors provided a carefully prepared illustration of the foot, which showed the gap between the hallux and second toe that we know today is characteristic of Down patients. More impressively, Fraser and Mitchell also provided the...