2011 William Allan Award introduction: John M. Opitz.

View Large Image | View Hi-Res Image | Download PowerPoint SlideAs a member of the awards committee of the American Society of Human Genetics, it is my privilege, great honor, and pleasure to introduce to you the winner of the 2011 William Allan Award: Dr. John M. Opitz.Dr. Opitz is unarguably a pioneer in the field of medical genetics. The year 2012 will mark 50 years of working in this field to which he has contributed over 500 publications in peer-reviewed journals. Dr. Opitz is a rare scholar and polyglot who speaks several languages in addition to his native German. He has used this knowledge to read texts in their original language and include pertinent references and ideas into his writings on embryology, fetal pathology, developmental biology, and medical genetics.Dr. Opitz is probably best known for working with patients and their families in order to observe and delineate many of the now classical genetic syndromes. He very well might be the single one geneticist who has described the most novel syndromes. In order to honor the patients rather than to call attention to the identifying clinician, Dr. Opitz named these syndromes after the first initials of the families that they affected, such as G syndrome,1xThe G syndrome of multiple congenital anomalies. Opitz, J.M., Frias, J.L., Gutenberger, J.E., and Pellett, J.R. Birth Defects Orig. Artic. Ser. 1969; 2: 95–101See all References1 BBB syndrome,2xThe BBB syndrome: Familial telecanthus with associated congenital anomalies. Opitz, J.M., Summitt, R.L., and Smith, D.W. Birth Defects Orig. Artic. Ser. 1969; 2: 86–94See all References2 FG syndrome,3xStudies of malformation syndromes of man 33: The FG syndrome. An X-linked recessive syndrome of multiple congenital anomalies and mental retardation. Opitz, J.M. and Kaveggia, E.G. Z. Kinderheilkd. 1974; 117: 1–18Crossref | PubMed | Scopus (63)See all References3 C syndrome,4xThe C syndrome of multiple congenital anomalies. Opitz, J.M., Johnson, R.C., McCreadie, S.R., and Smith, D.W. Birth Defects Orig. Artic. Ser. 1969; 2: 161–166See all References4 KBG syndrome,5xThe KBG syndrome-a syndrome of short stature, characteristic facies, mental retardation, macrodontia and skeletal anomalies. Herrmann, J., Pallister, P.D., Tiddy, W., and Opitz, J.M. Birth Defects Orig. Artic. Ser. 1975; 11: 7–18PubMedSee all References5 and many others. However, some of them now bear his name as in Smith-Lemli-Opitz syndrome6xA newly recognized syndrome of multiple congenital anomalies. Smith, D.W., Lemli, L., and Opitz, J.M. J. Pediatr. 1964; 64: 210–217Abstract | Full Text PDF | PubMedSee all References6 and Opitz syndrome (for GBBB syndrome). Not only did Dr. Opitz delineate novel syndromes in the 1960s, 70s, and 80s, but he also helped to understand the constellation of findings in the context of normal and abnormal embryological development. It was Dr. Opitz who rediscovered the concept of developmental field defect in humans,7xThe developmental field concept in clinical genetics. Opitz, J.M. J. Pediatr. 1982; 101: 805–809Abstract | Full Text PDF | PubMed | Scopus (83)See all References, 8xThe developmental field concept. Opitz, J.M. Am. J. Med. Genet. 1985; 21: 1–11Crossref | PubMedSee all References a concept that was previously described in amphibians by the German Nobel Laureate Hans Spemann. Over the past two decades, Dr. Opitz has been actively involved in the identification of the underlying genetic bases of the various syndromes that he had previously described.9xOpitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22. Quaderi, N.A., Schweiger, S., Gaudenz, K., Franco, B., Rugarli, E.I., Berger, W., Feldman, G.J., Volta, M., Andolfi, G., Gilgenkrantz, S. et al. Nat. Genet. 1997; 17: 285–291Crossref | PubMed | Scopus (246)See all References, 10xMutations in CD96, a member of the immunoglobulin superfamily, cause a form of the C (Opitz trigonocephaly) syndrome. Kaname, T., Yanagi, K., Chinen, Y., Makita, Y., Okamoto, N., Maehara, H., Owan, I., Kanaya, F., Kubota, Y., Oike, Y. et al. Am. J. Hum. Genet. 2007; 81: 835–841Abstract | Full Text | Full Text PDF | PubMed | Scopus (24)See all References, 11xA recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. Risheg, H., Graham, J.M. Jr., Clark, R.D., Rogers, R.C., Opitz, J.M., Moeschler, J.B., Peiffer, A.P., May, M., Joseph, S.M., Jones, J.R. et al. Nat. Genet. 2007; 39: 451–453Crossref | PubMed | Scopus (95)See all References The disease-associated genes of two of these syndromes, Bohring-Opitz syndrome (ASXL1)12xDe novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome. Hoischen, A., van Bon, B.W.M., Rodriguez-Santiago, B., Gilissen, C., Vissers, L.E.L.M., de Vries, P., Janssen, I., van Lier, B., Hastings, R., Smithson, S.F. et al. Nat. Genet. 2011; 43: 729–731Crossref | PubMed | Scopus (83)See all References12 and KBG syndrome (ANKRD11),13xMutations in ANKRD11 cause KBG syndrome, characterized by intellectual disability, skeletal malformations, and macrodontia. Sirmaci, A., Spiliopoulos, M., Brancati, F., Powell, E., Duman, D., Abrams, A., Bademci, G., Agolini, E., Guo, S., Konuk, B. et al. Am. J. Hum. Genet. 2011; 89: 289–294Abstract | Full Text | Full Text PDF | PubMed | Scopus (57)See all References13 were recently described.Dr. Opitz was the founding editor and, for 25 years, the editor-in-chief of the American Journal of Medical Genetics (1976–2001). Not only did he create a forum to exchange ideas between clinicians and basic scientists, but he was also a mentor to a generation of geneticists.Allow me to indulge in two brief personal examples. My interactions with Dr. Opitz began in 1987 when, as a clinical-genetics fellow at the Children's Hospital of Philadelphia, I had submitted my first manuscript on patients with holoprosencephaly.14xHoloprosencephaly: Association with interstitial deletion of 2p and review of the cytogenetic literature. Munke, M., Emanuel, B.S., and Zackai, E.H. Am. J. Med. Genet. 1988; 30: 929–938Crossref | PubMedSee all References14 Along with the reviewers' comments, I also received Dr. Opitz's feedback. I was reminded of the children's riddle, “What is black and white and re(a)d all over?” In the US, every parent of a 5–8-year-old child knows, of course, that the answer is “a newspaper.” After Dr. Opitz's edits with his famous “red pen,” the answer to “What is black and white and re(a)d all over?” was then “A manuscript edited by Dr. Opitz.”Another form of mentoring came when Dr. Opitz invited me to review several manuscripts on the topic of holoprosencephaly. When I was still in clinical-genetics training, he asked me to also write a review article to accompany the other holoprosencephaly manuscripts.15xClinical, cytogenetic, and molecular approaches to the genetic heterogeneity of holoprosencephaly. Munke, M. Am. J. Med. Genet. 1989; 34: 237–245Crossref | PubMedSee all References15 This was the push that I needed to start investigating the underlying causes of normal and abnormal brain development. And that is what my lab has focused on for the past two decades. So, it is no exaggeration to state that my career was shaped and defined by Dr. Opitz's early encouragement. I know of several other colleagues who had a similar career boost from Dr. Opitz.In closing, let me tell you about Dr. Opitz's love of nature and, most of all, his dedication to his patients and their families. I have witnessed this personally at a weekend with a support group for parents who had children with various intellectual and/or physical disabilities. His warmth, caring, and compassion had a healing effect on the families even when little else could be offered from the medical field.Join me in celebrating a giant in the field of medical genetics, Dr. John Opitz, the winner of the 2011 William Allan Award!