Pallister–Killian syndrome: Historical perspective and foreword

There have been quite some changes since I first became aware of genetics. In high school biology in 1938 we were taught that there were 48 human chromosomes just as we were at the University of Minnesota from 1938 to 1944. But in other parts of the world human chromosomes had been of interest for some time. Lionel Sharples Penrose and coworkers worked at the Royal Eastern Counties Institute for 7 years; they examined 1,280 patients with ‘‘mental deficiency’’; took 400 family histories and examined 6,629 parents and sibs. He finished this work at Colchester in 1934 and published his first book based on that study when I was 13 [Penrose, 1934]. In 1939hepublishedapaper concluding that aging mothers were more apt to have a ‘‘mongoloid child,’’ that birth order was significant and that ‘‘mongolism and some other malformations may have their origins in chromosome abnormalities.’’ I was a pre-med sophomore at the University of Minnesota. Petrus Waardenburg had suggested this in, 1932 as did others including Raymond Turpin in France. After sometime spent as a United States Army physician, my wife and I determined never to live in a large city again; we moved to Boulder,Montana in 1947 for a life of a general practitioner. Part of my practice included responsibility for the health and welfare of the patients at the state institution for the ‘‘feeble-minded,’’ ‘‘retarded,’’ ‘‘mentally deficient,’’ ‘‘developmentally impaired,’’ and so on. Penrose [1949] published the book that fell into my hands in 1956. Initially therewere 487patients inBoulder but as our program developed we peaked at 1,187 ‘‘residents.’’ Eventually several thousand were studied here, around the state and especially at theShodairGeneticCenter inHelenaduring the last 7 yearsof our active medical life. As a General Practitioner, my interest was in developing diagnostic tools, rehabilitation programs, chromosome labs, biochemical screening, autopsy and neuropathology studies, electroencephalography, brain scanning, the natural history of disorders, drug and vaccine trials, writing laws to enhance the care of our patients, screening newborn infants for treatable, and untreatable conditions. And especially in the wide use of consultants (many of the world’s greatest human geneticists came to Boulder) was to better understand and to treat my patients. And while I began these efforts, changes were taking place in human chromosome knowledge. In 1953 Murray Barr distinguished the Barr body, the resting X chromosome on the nuclearmembrane of cat neurones, a subject he had been interested in since 1949 [Barr and Bertram, 1949]. On December 22, 1955 Joe Hin Tjio, ‘‘working in the laboratory ofAlbert Levan at 2 in themorning’’ inLund, Swedendemonstrated that the human normal chromosome number was 46. Levan had developed the techniques including theuseof colchicine to improve metaphase spreads while studying plant cytology [Tjio and Levan, 1956]. Levan’s improved cell culture methods soon spread; at Harvard University Benedikt F. Massel, interested in rheumatoid arthritis (RA) and rheumatic heart disease, attracted the attention of a young French woman,Marthe Gautier, with similar interests. Gautier was incidentally trained in tissue culture in his lab while growing cells from aortic tissue removed in surgery. Returning to Paris she set up the laboratory for Raymond Turpin to determine the chromosome number in Down syndrome patients. Turpin had obtained tissue samples from patients but since they had no photomicrograph they turned to Jerôme Lejeune for the photography [Gilgenkrantz and Rivera, 2003]. Lejeune had been interested in the chromosomes of Down patients for some time andhadmade anoral presentation regarding the extra chromosome in 1958 at an English seminar and now the three collaborated in the famous 1959 publications demonstrating the extra 21 chromosome as cause of Down syndrome (Lejeune commented the extra chromosome appeared to be one of the smallerGsor the 22ndpair) [Lejeune et al., 1959a,b]. By convention it has been agreed to call it the 21st pair. In 1959 at the Hartford Connecticut meeting of AAMD (American Association on Mental Deficiency—now the AAIDD— American Association of Intellectual and Developmental