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As a teenager just moved to Iowa from war-ravaged Germany in 1951, John M. Opitz, M.D., wanted to study developmental biology, but his “very Prussian” mother insisted he go to medical school instead. 

In the intervening 50-plus years, the wisdom of this mother’s insistence has been born out. The medical geneticist and professor of pediatrics at the University of Utah School of Medicine has become one of the world’s foremost authorities in medical genetics, the medical discipline dedicated to identifying, treating, and understanding genetic disorders, some of them so rare that only a handful of people worldwide are known to have them.

Opitz’s phone rings daily with calls from physicians around the globe seeking information about genetic syndromes: What are the physical and biological characteristics of particular disorders? How are they treated? What causes them? Few in his field have contributed as much to ascertaining those answers for patients and doctors as Opitz, who joined the U of U faculty in 1997. In recognition of his seminal contributions to medical genetics the past four-plus decades, Opitz will be honored with the American Society of Human Genetics’ (ASHG) highest honor – the William Allan Award – at the 12th International Congress of Human Genetics/ASHG 61st Annual Meeting on Oct. 13, 2011, in Montreal.

Opitz has defined and documented numerous genetic syndromes, some of which bear his name, pioneered phenotyping, or identifying the physical and biological manifestations of genetic disorders, and laid foundational work for finding genes associated with a number of genetic disorders. In the process, he has built the framework for medical geneticists worldwide to learn how to analyze phenotypes. Named for William Allan, a pioneering American physician in undertaking extensive research in human genetics, the Allan Award is given annually to a scientist who has made far-reaching contributions to human genetics for a sustained period.

“John Opitz is one of the most well-respected and forward-thinking geneticists in the field,” said ASHG executive vice president, Joann Boughman, Ph.D. “ASHG would like to recognize Dr. Opitz for his substantial and far-reaching scientific contributions that have had a significant impact on human genetics research. He is being honored as the recipient of this year’s William Allan Award – the top prize that is given annually by ASHG – for the revolutionary advances that he has made in medical genetics.

Harry Ostrer, M.D., chair of the ASHG Awards Committee, professor of pathology and genetics at Albert Einstein College of Medicine and director of genetic and genomic testing at Montefiore Medical Center, said his landmark work in phenotyping and identifying new genetic syndromes made Opitz the unanimous choice for the award. “In this genomic era, the genetics is easy, but the phenotypes are hard,” Ostrer says. “Phenotypes were always hard, but Dr. Opitz has a great eye and a great memory.”

The 76-year-old Opitz, who’s tall, slender figure is unmistakable as he walks the halls of University of Utah Hospital and Primary Children’s Medical Center in Salt Lake City, says identifying genetic syndromes has never been his primary objective. “My goal simply has been to care for the patients and their families,” he says.

Born in Hamburg, Germany, not far from the North Sea, his life was indelibly shaped by World War II. When the Allied bombs began dropping on Hamburg when he was still a young child, his native city was left in ruins. The soft-spoken Opitz, whose voice still carries a German accent, remembers as a child looking out over his hometown as buildings flamed and corpses lay on the streets. “One becomes a survivor,” he says, pausing. “Life as a survivor is very difficult.”

Shortly after the war started, Opitz and his mother were separated for nearly seven years. He contracted tuberculosis and spent several years in a sanatorium, much of it in isolation because of the highly contagious nature of his illness. After regaining his health, he went to Nuremburg to live with his mother. But, unable to care for him in that bomb-ravaged city, she sent young Opitz to live with his grandfather until the war ended. Finally, in 1945, he was reunited with his mother and lived in Nuremburg for six years while she served as a U.S. interpreter during the war-crimes trials.

In 1951, they immigrated to Iowa City, where his uncle was a professor of ‘cello at the . Opitz immediately took to his new country. “There was something about America,” he says. “Its openness and the kindness and goodness of the people – even to a child former enemy – appealed to me.”

He studied zoology at the University of Iowa under Emil Witschi, a renowned zoologist and expert in genetics, developmental biology, and evolution, and began medical school at Iowa in 1955. After graduating in 1959, he began his residency and then fellowship in pediatrics at the University of Wisconsin, where he studied under Klaus Patau, Ph.D., a pioneer in medical genetics, and David W. Smith, M.D., considered the father of dysmorphology – the study of structural defects, particularly congenital malformations, in people. Smith introduced Opitz to a facility in Wisconsin where severely mentally disabled children and adults lived, and shortly after that he began his life’s work of learning to recognize physical and biological signs and symptoms of disorders to diagnose and understand them. When patients died, he took part in the autopsies to learn the biological basis of their disorders, something he continues to this day.

At that time, in the early 1960s, Opitz devoted himself to understanding the genetic, developmental, and evolutionary factors that influence abnormal human development. This, combined with his observations of patients, says his U of U colleague John C. Carey, M.D., a medical geneticist and professor of pediatrics, allowed Opitz to begin laying the foundation for clinical genetics, delineating phenotypes, and identifying numerous syndromes, including:

• Smith-Lemli-Opitz syndrome (SLOS), a development disorder caused by a defect in the way cholesterol is synthesized, which can result in profound mental disability, learning and behavioral problems and physical malformations and maladies such as  fused second and third toes or extra fingers and toes;  malformations in the heart, lungs, and kidneys; microcephaly (small head), and numerous other medical issues. SLOS is an autosomal recessive disorder passed on when each parent possesses a mutated copy of the DHCR7 gene.
• Opitz G/BBB syndrome, a condition with two forms with physical malformations that include wide-spaced eyes; defects of the larynx; trachea; and esophagus; heart defects; absence of tissue connecting the left and right halves of the brain, and other issues. The X chromosome-linked form of the syndrome occurs only in males and is caused by a mutation in the MID1 gene. It is estimated to affect between one in 50,000 to 100,000 males. Incidence of the autosomal dominant form of the disorder is unknown.
• C syndrome, an extremely rare disorder in which severe mental disability is common, along with physical malformations that include a triangular shaped head, caused by the premature union of the skull bones; narrow pointed forehead; flat nasal bridge; short nose; abnormalities of the ear; loose skin, and other problems. This syndrome is estimated to occur in one in 800,000 to 1 million people.
• Opitz-Kaveggia (FG) syndrome, an X chromosome-related disorder that affects intelligence, behavior, and causes a range of physical malformations and maladies, including a large head (macroencephaly); heart defects; seizures; weak muscle tone; broad thumbs and toes; widely set eyes; abnormalities in the tissue connecting the left and right halves of the brain; small ears, and downward pointing outside corners of the eye. A mutation in the MED12 gene and six regions of the X chromosome have been linked to FG syndrome. Although the prevalence of the disorder is not known, only several hundred cases have been reported worldwide.

Amid his landmark work that began in the 1960s and that has continued for decades, Opitz also founded the American Journal of Medical Genetics in 1976, becoming its first editor-in-chief and remaining in that position until 2001. A highly regarded forum for scholarly analysis of phenotypes of genetic disorders, the first volume appeared in 1977. Initially, the journal was published quarterly, but the reception and demand for it led to monthly publication the following year. Opitz stepped down as editor-in-chief in 2001 and was succeeded by Carey.

“The seminal work of Dr. Opitz extends to the early days of the history of what we now consider clinical genetics,” says Carey, his longtime colleague. “He is unarguably a pioneer in the field and the time has come to recognize one of the giants of human genetics.”

Maximillian Muenke, M.D., chief of medical genetics at the National Institutes of Health’s Genome Research Institute, has known Opitz for 25 years through the AJMG and will introduce him at the Montreal award ceremony. He describes Opitz as a rare scholar and polyglot who speaks German and reads ancient, Medieval, and modern texts in Latin, French, and Italian. But, in addition, his broad training and background in embryology, anatomy, pathology, developmental biology, and other disciplines means he understands the “language” of those fields.

In combination, those talents allow Opitz to “go back and forth in time and mother tongues and professions” to pursue his work in ways that few researchers and physicians can do. Above all this, he never loses sight of the patients he serves. “He is a most compassionate physician and is adored by the families and patients he has seen for almost 50 years,” Muenke says. “The only surprise is that he didn’t receive this award 25 years ago.”