American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 166C:381–386 (2014)
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The Shodair Medical Genetics Department—Recent Past and Future Developments ABDALLAH F. ELIAS*
Philip Pallister and John Opitz laid the ground work for a unique genetic service model in Montana that continues to flourish through ongoing support by the Montana Legislature, the Montana Department of Public Health and Human Services and the Shodair Foundation. At the heart of the model are clinical and laboratory genetic specialists based at Shodair Children's Hospital in Helena providing genetic care for patients through outreach clinics. Clinical services are supported by a state‐of‐the‐art cytogenetics and molecular genetic laboratory as well a fetal genetic pathology program. Over the years, the reach of regular genetics clinics expanded to include large geographic areas including northwest (Kalispell), west central (Missoula), southwest (Bozeman, Butte), north central (Great Falls), and south central Montana (Billings). Building on the foundation of its world‐renowned pioneers, the next generation of medical geneticists at Shodair carries the responsibility of integrating genomic medicine in the diagnosis and care of their patients, reducing inequality of services within Montana and partnering with colleagues across specialties to develop a more personalized practice of medicine. © 2014 Wiley Periodicals, Inc. KEY WORDS: Shodair Hospital; Philip Pallister; medical genetics
How to cite this article: Elias AF. 2014. The Shodair Medical Genetics Department—Recent past and future developments. Am J Med Genet Part C 166C:381–386.
RECENT PAST When John Opitz left for the University of Utah, the ground work for a unique genetic service model had been laid— the Montana Genetics Program. At the heart of this model were clinical and laboratory genetic specialists based at Shodair Children’s Hospital in Helena providing genetic services through outreach clinics. Clinical services were supported by a state‐of‐the‐art cytogenetics laboratory and the Montana Fetal Genetic Pathology Program.
At the heart of this model were clinical and laboratory
genetic specialists based at Shodair Children’s Hospital in Helena providing genetic services through outreach clinics. Clinical services were supported by a state‐of‐the‐art cytogenetics laboratory and the Montana Fetal Genetic Pathology Program. John P. Johnson, M.D., succeeded John Opitz as the medical director of the Montana Medical Genetics Program in
1994 and joined James F. Reynolds, M.D., a pediatrician and clinical geneticist who had come to Shodair as the replacement for Dr. Pallister in 1983. A graduate from the University of Michigan Medical School, Dr. Johnson completed a residency in pediatrics at the Children’s Hospital of Los Angeles, CA, and later a medical genetics fellowship at the University of Utah under the mentorship of Dr. John C. Carey. He held positions as director of medical genetics at the Children’s Hospital of Oakland, CA and was a faculty member at Primary Children’s Hospital and the University of Utah. Prior to becoming a geneticist, Dr. Johnson practiced general pediatrics and
Abdallah F. Elias, M.D., FACMG, is director of Medical Genetics at Shodair Children's Hospital. A board‐certified clinical geneticist, family physician, and trained pediatrician, he is a former fellow in Clinical Genetics at the McKusick‐Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine. He is affiliate professor at the University of Montana, Department of Biomedical & Pharmaceutical Sciences and affiliate clinical faculty at the Western Montana Family Medicine Residency Program in Missoula, MT. He initially came to Montana as a scientist at the Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). *Correspondence to: Abdallah F. Elias, M.D., FACMG Medical Director, Department of Medical Genetics, Shodair Children's Hospital, 2755 Colonial Drive, Helena, MT 59601‐4926. E‐mail: [email protected] DOI 10.1002/ajmg.c.31417 Article first published online in Wiley Online Library (wileyonlinelibrary.com): 25 November 2014
ß 2014 Wiley Periodicals, Inc.
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was Chief of Pediatrics at Family Health Plan in Salt Lake City, UT. He continues as a consultant for Shodair and is involved in publications with the group [Johnson et al., 1983; Pallister et al., 2011; Hudson et al., 2014]. Dr. Reynolds graduated from the University of Louisville School of Medicine and completed a pediatric residency at the University of Virginia in Charlottesville. He then trained in medical genetics under the mentorship of Dr. Thadeus Kelly at the University of Virginia. He joined the staff of Shodair Hospital directly from his fellowship. Dr. Reynolds served as the associate editor of the American Journal of Medical Genetics until John Opitz left, and Dr. Reynolds directed the Fetal Genetic Pathology program after his departure. He was the first author on the initial description of the cardio‐facio‐cutaneous syndrome [Reynolds et al., 1986]. During Dr. Johnson’s tenure at Shodair, the reach of regular genetics clinics expanded from west central Montana (Missoula) and south central Montana (Billings) to include southwest Montana (Bozeman, Butte), north central Montana (Great Falls), and northwest Montana (Kalispell). In order to meet the increased demand for genetic services, the number of genetic counselors more than doubled from two in 1994 to five in 2013 (Katherine Berry, Cindy Hudson, Tessa Pitman, Jaclyn Foster, Marissa Clark) (Fig. 2). The need for cancer genetic counseling born of advances in cancer genetics and genetic testing prompted the start of a counseling program for individuals at‐risk for a hereditary cancer syndrome. The program was overseen by Dr. Reynolds initially following the outreach model and more recently utilizing telemedicine.
The need for cancer genetic counseling born of advances in cancer genetics and genetic testing prompted the start of a counseling program for
individuals at‐risk for a hereditary cancer syndrome. Molecular cytogenetic techniques and routine fluorescent in situ hybridization (FISH) had been available at Shodair, but the molecular genetic diagnostic laboratory developed to its current state during Dr. Johnson’s tenure. Board‐certified in clinical and clinical molecular genetics, he oversaw the introduction of a broad range of molecular diagnostic assays covering neurodevelopmental, neurodegenerative, and growth disorders, as well as hereditary coagulopathies. With the current team of molecular genetics laboratory technicians, Katie Styren, Jon Schoof and Corbin Schwanke (Fig. 2), chromosomal microarray (CMA) and pharmacogenetic testing of drug metabolism were implemented. The Shodair molecular laboratory remains the only provider in Montana to offer constitutional CMA, ensuring timely access to what now is considered first‐tier genetic testing for children with developmental delays, autism spectrum disorders and congenital anomalies. Pharmacogenetics has since become an integral to the management of children treated in Shodair’s one acute and three residential child and adolescent psychiatric treatment units. The Medical Genetics Department has continued to play an important role in local and regional genetics education and training. As an official site for WWAMI of the University of Washington, a nationally and internationally recognized model for training physicians and other health professionals for rural areas, genetics staff are teaching third‐year medical students rotating through the genetics clinic. Through a collaboration with the University of Utah Graduate Program in Genetic Counseling, genetic counseling students participate in outreach genetic clinics during summer rotations. The Shodair laboratory also regularly hosts students from the University of Cincinnati, a connection established by former laboratory director Mary M. Haag, Ph.D. In addition, an educational program
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offers both local high school students and Helena’s Carroll College students unique opportunities to gain experience in the genetic laboratory. Initiated by John Opitz, the medical library maintains an extensive collection of medical journals, yearbooks and textbooks with primary focus on medical genetics, genomics and neuropsychiatric topics. A total of 63 genetics titles is currently available as print copies and online, many of which are unavailable elsewhere in Montana, underscoring the library’s role as a regional educational resource. In 2008, the State of Montana mandated expanded newborn screening to the 28 core conditions recommended by the American Academy of Pediatrics and American College of Medical Genetics in 2006. Until then, the newborn screening follow‐up had been coordinated by the clinical geneticists at Shodair supported by biochemical geneticists from the Universities of Oregon (Neil Buist) and Colorado (Janet Thomas). In response to the increased numbers of patients diagnosed with metabolic conditions neonatally, a comprehensive newborn screening follow‐ up program was established after the arrival of Samuel Yang, M.D. (Fig. 2), a board certified clinical and biochemical geneticist. He joined Shodair in 2010 after holding positions at Lanterman Developmental Center in Pomona, California, the Permanente Medical Group in San Francisco, Children’s Hospital of Los Angeles, and the California Department of Developmental Services. Dr. Yang is a graduate of Johns Hopkins School of Medicine. He trained in pediatrics at Stanford Medical Center and U.C. Davis Medical Center, followed by a fellowship in medical genetics at Children’s Hospital of Central California [Yang et al., 1997; South et al., 2010].
In 2008, the State of Montana mandated expanded newborn screening to the 28 core conditions recommended by the American Academy of
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Pediatrics and American College of Medical Genetics in 2006. The newborn screening follow‐up is coordinated and performed by an interdisciplinary team encompassing a biochemical geneticist, a metabolic dietician, a genetic counselor, a clinical psychologist, and a nurse coordinator. Patients and families are seen in metabolic clinics throughout the state including Missoula, Kalispell, Great Falls, Helena, Bozeman, and Billings. More recently, Dr. Abdallah Elias (Fig. 2) was involved as a consultant to the Department of Public Health and Human Services (DPHHS) in the development of administrative rule changes that allowed for the introduction of mandated neonatal screening for critical congenital heart disease (CCHD) by the State of Montana in 2014 (Fig. 1).
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CURRENT AND FUTURE DEVELOPMENTS Today, the medical genetics program at Shodair continues to have the strong support of its Board of Directors and Hospital Administrator of 27 years Jack Casey (Fig. 2), a trained laboratory technologist who was the genetics laboratory director back in 1970 and whose roots are deeply tied to Drs. Pallister and Opitz and the Montana Genetics Program. In 2012, Dongbin Xu, Ph.D. (Fig. 2), became director of the laboratory at Shodair Children’s Hospital after completing a fellowship in cytogenetics at The Children’s Hospital of Philadelphia (CHOP) where he was trained in clinical cytogenetics by Dr. Nancy Spinner and worked with Dr. Ian Krantz to establish a Drosophila model and an induced pluripotent stem cell model for investigating molecular genetic mechanisms underlying Cornelia de Lange syndrome [Xu and Krantz, 2012]. He earned his doctorate in biomedical science at the University of Texas
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M.D. Anderson Cancer Center at Houston. Born in China, Dr. Xu became a research assistant at Huazhong University of Science and Technology in Wuhan and graduate student at the Institute of Genetics in Fudan University at Shanghai, China before continuing his career in the United Sates. As a board‐certified clinical cytogeneticist with research experience in Drosophila genetics and stem cells, he brings to Shodair extensive experience in cytogenetic and molecular genetics. With particular interest in the cytogenetics and molecular cytogenetics of cancer, he and his staff (Karen Ellsworth, Joan Fitzgerald, Sandy Philips, Tammy Schwalbe, Mary Tunby, June Warner,and Amy Zearfos) (Fig. 2) offer a comprehensive panel for the diagnosis of hematologic cancers in addition to cytogenetic and molecular genetic tests for the diagnosis of a variety of hereditary genetic disorders. After 19 years at Shodair, Dr. Johnson moved to Boston, MA in 2013 where he became Chief of the Division of Genetics and Metabolism at
Figure 1. Map of Montana showing patients and their families (pink dots) by Montana City (red square). Shodair Children’s Hospital is located in Helena, Montana’s capital. Regular genetics clinics are held in Helena, Missoula, Kalispell, Great Falls, Bozeman, Butte, Billings. Periodic clinics are also held in Browning and Miles City.
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Figure 2. The Department of Medical Genetics, Shodair Children’s Hospital. Front row from left to right: Jaclyn Foster, Brittney Rio, Katie Styren, Tammy Schwalbe, Dongbin Xu, Sara Wakefield, Sandra Phillips, and June Warner; Back row from left to right: Katherine Grover, Samuel Yang, Tracy Wollett, Jonathan Shoof, Ellen Livers, José Camacho, Jack Casey, Abdallah Elias, Mary Tunby, Amy Zearfoss, Karen Ellsworth, Katherine Berry, and Cindy Hudson. Not in the photo: Corbin Schwanke and Marissa Clark.
Tufts Medical Center and a professor at Tufts University School of Medicine. After a tenure of 31 years at Shodair, Dr. Reynolds became interim‐director until his retirement in June 2014. A West Point graduate, Dr. Reynolds also retired from the U.S. Army as a brigadier general in 2006 after over 30 years of service and tours of duty in Vietnam, Boznia and Herzegovina, and Iraq. Abdallah F. Elias, M.D. (Fig. 2) joined the department in 2013 and became medical director of the Genetics Department at Shodair Children’s Hospital in June 2014. He is affiliate professor at the University of Montana, Department of Biomedical and Pharmaceutical Sciences and affiliate clinical faculty at the Western Montana Family Medicine Residency Program in Missoula, Montana, which is part of the WWAMI program. Dr. Elias completed a residency and fellowship in Clinical Genetics at the
McKusick‐Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine in Baltimore, MD. Under the mentorship of Dr. David Valle and Dr. Hal Dietz, he used genome‐wide approaches including genome‐wide linkage studies and next‐generation sequencing (NGS), to identify disease‐associated genetic variants in families with highly penetrant dominant familial thoracic aortic aneurysms/dissections. This contributed to the identification of loss‐of‐ function mutations in TGF beta 2 as a cause for syndromic familial aortic aneurysms [Lindsay et al., 2012]. Originally from Germany, Dr. Elias received his medical degree from the University of Freiburg in Germany and completed a pediatrics residency at the Children’s Hospital of the University of Freiburg in Germany, as well as training in Family Medicine at the University of South Dakota. He came to Montana initially as
a visiting scientist at the Rocky Mountain Laboratories, NIAID, NIH in Hamilton, MT, where Willi Burgdorfer had discovered the cause of Lyme disease in 1982 subsequently named after him. Elias demonstrated the feasibility of transforming infectious Borrelia burgdorferi in the laboratory of Patricia Rosa, laying the ground work for studying mutant bacteria in the experimental mouse‐tick infectious cycle [Elias et al., 2002]. José A. Camacho, M.D. (Fig. 2), who recently joined Shodair as a clinical geneticist, brings to the team a unique set of clinical and research experience. Prior appointments included positions in Pediatric Genetics and Metabolism at Miller Children’s Hospital in Long Beach, CA, Children’s Hospital of Orange County in Orange, CA, and the University of California, Irvine (UCI) Medical Center, where he also was an assistant professor. He has a special interest in
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mitochondrial disorders and was a faculty member at the Center for Molecular and Mitochondrial Medicine and Genetics (MAMMAG) and director of both the Mitochondrial Biochemical Diagnostics Laboratory and MITOMED, the clinical arm for MAMMAG at the UCI. He completed a fellowship in clinical genetics at the McKusick‐Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine in Baltimore, MD, where he also worked on molecular genetics of urea cycle disorders in Dr. Valle’s group. His work led to the identification of ORNT1 as the gene responsible for the hyperornithinemia‐ hyperammonemia‐homocitrullinuria (HHH) syndrome [Camacho et al., 1999]. After receiving his medical degree from the Universidad Central del Caribe (UCC) School of Medicine in San Juan, Puerto Rico, and completing a residency in pediatrics at the University of Missouri in Columbia, MO, he continued fellowship training in pediatric cardiology at Schneider’s Children’s Hospital of Long Island Jewish Medical Center and the University of Iowa, and was also a research scientist in the Department of Pharmacology of Columbia University College of Physicians and Surgeons. Coming to Shodair, Dr. Camacho brings an interest in translational approaches to integrate complex physiological and metabolic processes and genomic information to improve our understanding of complex diseases. As described in the preceding section, the Medical Genetics Department underwent important changes within the last few months and years prompted by both internal and external developments. These developments come at a time when the classic specialty of clinical genetics itself is undergoing a fundamental transformation. Increasingly, genomic approaches to the diagnosis of rare and common disorders are feasible in the clinical setting and are becoming accessible to a wider population. This is reflected not the least in the recent name change of ACMG to the American College of Medical Genetics and Genomics. Previously practicing predominantlyas diagnostic specialists, clinical geneticists are becoming involved in the management and care of patients across all
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age groups, often in close collaboration with other specialists and subspecialists. Examples of these developments are the involvement of geneticists in the management of individuals with neurodevelopmental, neuropsychiatric and neurodegenerative disorders, genetic epilepsies, and genetic‐ metabolic disorders for which targeted therapies are coming within reach. Such shifts have particular impact in the health care setting of Montana, which on the one hand is characterized by mostly rural communities, few urban centers separated by vast geographic spaces, high prevalence of underserved communities and low‐ income populations. On the other hand, Montana has a robust primary care based model of health care delivery which is constantly being enhanced by a growing number and diversification of specialists and sub‐specialists, allowing increasingly for the local management of patients with complex health problems.
These developments come at a time when the classic specialty of clinical genetics itself is undergoing a fundamental transformation. Increasingly, genomic approaches to the diagnosis of rare and common disorders are feasible in the clinical setting and are becoming accessible to a wider population. This is reflected not the least in the recent name change of ACMG to the American College of Medical Genetics and Genomics. It is in this context that the next generation of medical geneticists at Shodair is faced with the challenging responsibility of integrating genomic medicine in the diagnosis and care of their patients, reduce inequality of
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services within Montana and partner with colleagues across specialties to develop a more personalized practice of medicine (Fig. 2). One of the major developments at Shodair is the planned implementation of Next Generation Sequencing to allow for phenotype‐ driven analysis of genomic data early in the diagnostic process of complex disorders. In a setting where availability and geographic distances are impeding timely specialist evaluations, early phenotype/ genotype‐guided clinical evaluation— rather than exhaustive diagnostic odysseys preceding genetic testing—may be more cost efficient and improve patient care.
It is in this context that the next generation of medical geneticists at Shodair is faced with the challenging responsibility of integrating genomic medicine in the diagnosis and care of their patients, reduce inequality of services within Montana and partner with colleagues across specialties to develop a more personalized practice of medicine. Other developments and projects are being pursued at Shodair on several levels. The diagnosis and management of children with neurodevelopmental and neurobehavioral phenotypes were enhanced with the integration of formal neuropsychological evaluations by Dr. Christa Smelko, clinical psychologist, within the Medical Genetics Department. An increasing number of mitochondrial conditions have been identified and are being managed by the metabolic disorders team, and dedicated mitochondrial clinics are being implemented. Telemedicine, facilitated by several health telemedicine networks, has become an integral part in the delivery of genetic services within the
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Shodair model. Initially used for genetic counseling visits, its utility in assuring continuity of care and co‐managing patients with other providers is becoming increasingly recognized in the context of Montana’s challenging geography. In a similar development, the outreach of the department has recently further expanded by the addition of a genetic counselor at a satellite location in Kalispell, the regional health care hub of Northwestern Montana. The counselor not only coordinates and participates in on‐site and telemedicine genetic visits, but also is involved in outreach, needs assessment and education of underserved communities. Building on the foundation of its world‐renowned pioneers, the Montana Genetics Program is poised to flourish through ongoing support by the Montana Legislature, the Montana Department of Public Health and Human Services and the Shodair Foundation.
ACKNOWLEDGMENTS The author is grateful for the insight and knowledge gained from interviews with Jack Casey, John Johnson, Sandy Phil-
lips, Jim Reynolds, Dongbin Xu, Jose Camacho and Samuel Samuel Yang. Many individuals who were part of Shodair’s recent history remained unnamed and are hereby acknowledged.
REFERENCES Camacho JA, Obie C, Biery B, Goodman BK, Hu CA, Almashanu S, Steel G, Casey R, Lambert M, Mitchell GA, Valle D. 1999. Hyperornithinaemia‐hyperammonaemia‐homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter. Nat Genet 22:151–158. Elias AF, Stewart PE, Grimm D, Caimano MJ, Eggers CH, Tilly K, Bono JL, Akins DR, Radolf JD, Schwan TG, Rosa P. 2002. Clonal polymorphism of Borrelia burgdorferi strain B31 MI: Implications for mutagenesis in an infectious strain background. Infect Immun 70:2139–2150. Hudson C, Schwanke C, Johnson JP, Elias AF, Phillips S, Schwalbe T, Tunby M, Xu D. 2014. Confirmation of 6q21‐6q22. 1 deletion in Acro‐cardio‐facial syndrome and further delineation of this contiguous gene deletion syndrome. Am J Med Genet Part A 164A:2109–2113. Johnson JP, Carey JC, Gooch WM III, Petersen J, Beattie JF. 1983. Femoral hypoplasia‐unusual facies syndrome in infants of diabetic mothers. J Pediatr 102:866–872. Lindsay ME, Schepers D, Bolar NA, Doyle JJ, Gallo E, Fert‐Bober J, Kempers MJ, Fishman EK,
ARTICLE Chen Y, Myers L, Bjeda D, Oswald G, Elias AF, Levy HP, Anderlid BM, Yang MH, Bongers EM, Timmermans J, Braverman AC, Canham N, Mortier GR, Brunner HG, Byers PH, Van Eyk J, Van Laer L, Dietz HC, Loeys BL. 2012. Loss‐of‐function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nat Genet 44:922–927. Pallister PD, Pallister AB, South S, Toydemir R, Johnson JP, Beischel L, Opitz JM. 2011. A deletion 13q34/duplication 14q32.2‐14q32.33 syndrome diagnosed 50 years after neonatal presentation as infantile hypercalcemia. Am J Med Genet Part A 155A:833–839. Reynolds JF, Neri G, Herrmann JP, Blumberg B, Coldwell JG, Miles PV, Opitz JM. 1986. New multiple congenital anomalies/mental retardation syndrome with cardio‐facio‐ cutaneous involvement—The CFC syndrome. Am J Med Genet 25:413–427. South ST, Rector L, Aston E, Rowe L, Yang SP. 2010. Large clinically consequential imbalances detected at the breakpoints of apparently balanced and inherited chromosome rearrangements. J Mol Diagn 12: 725–729. Xu D, Krantz ID. 2012. Cohesin and human diseases. In: Ahituv N, editor. Regulatory sequences and human disease. New York: Springer. pp. 217–251. Yang SP, Bidichandani SI, Figuera LE, Juyal RC, Saxon PJ, Baldini A, Patel PI. 1997. Molecular analysis of deletion (17) (p11.2p11.2) in a family segregating a 17p paracentric inversion: Implications for carriers of paracentric inversions. Am J Hum Genet 60:1184–1193.
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The Shodair Medical Genetics Department—Recent Past and Future Developments ABDALLAH F. ELIAS*
Philip Pallister and John Opitz laid the ground work for a unique genetic service model in Montana that continues to flourish through ongoing support by the Montana Legislature, the Montana Department of Public Health and Human Services and the Shodair Foundation. At the heart of the model are clinical and laboratory genetic specialists based at Shodair Children's Hospital in Helena providing genetic care for patients through outreach clinics. Clinical services are supported by a state‐of‐the‐art cytogenetics and molecular genetic laboratory as well a fetal genetic pathology program. Over the years, the reach of regular genetics clinics expanded to include large geographic areas including northwest (Kalispell), west central (Missoula), southwest (Bozeman, Butte), north central (Great Falls), and south central Montana (Billings). Building on the foundation of its world‐renowned pioneers, the next generation of medical geneticists at Shodair carries the responsibility of integrating genomic medicine in the diagnosis and care of their patients, reducing inequality of services within Montana and partnering with colleagues across specialties to develop a more personalized practice of medicine. © 2014 Wiley Periodicals, Inc. KEY WORDS: Shodair Hospital; Philip Pallister; medical genetics
How to cite this article: Elias AF. 2014. The Shodair Medical Genetics Department—Recent past and future developments. Am J Med Genet Part C 166C:381–386.
RECENT PAST When John Opitz left for the University of Utah, the ground work for a unique genetic service model had been laid— the Montana Genetics Program. At the heart of this model were clinical and laboratory genetic specialists based at Shodair Children’s Hospital in Helena providing genetic services through outreach clinics. Clinical services were supported by a state‐of‐the‐art cytogenetics laboratory and the Montana Fetal Genetic Pathology Program.
At the heart of this model were clinical and laboratory
genetic specialists based at Shodair Children’s Hospital in Helena providing genetic services through outreach clinics. Clinical services were supported by a state‐of‐the‐art cytogenetics laboratory and the Montana Fetal Genetic Pathology Program. John P. Johnson, M.D., succeeded John Opitz as the medical director of the Montana Medical Genetics Program in
1994 and joined James F. Reynolds, M.D., a pediatrician and clinical geneticist who had come to Shodair as the replacement for Dr. Pallister in 1983. A graduate from the University of Michigan Medical School, Dr. Johnson completed a residency in pediatrics at the Children’s Hospital of Los Angeles, CA, and later a medical genetics fellowship at the University of Utah under the mentorship of Dr. John C. Carey. He held positions as director of medical genetics at the Children’s Hospital of Oakland, CA and was a faculty member at Primary Children’s Hospital and the University of Utah. Prior to becoming a geneticist, Dr. Johnson practiced general pediatrics and
Abdallah F. Elias, M.D., FACMG, is director of Medical Genetics at Shodair Children's Hospital. A board‐certified clinical geneticist, family physician, and trained pediatrician, he is a former fellow in Clinical Genetics at the McKusick‐Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine. He is affiliate professor at the University of Montana, Department of Biomedical & Pharmaceutical Sciences and affiliate clinical faculty at the Western Montana Family Medicine Residency Program in Missoula, MT. He initially came to Montana as a scientist at the Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). *Correspondence to: Abdallah F. Elias, M.D., FACMG Medical Director, Department of Medical Genetics, Shodair Children's Hospital, 2755 Colonial Drive, Helena, MT 59601‐4926. E‐mail: [email protected] DOI 10.1002/ajmg.c.31417 Article first published online in Wiley Online Library (wileyonlinelibrary.com): 25 November 2014
ß 2014 Wiley Periodicals, Inc.
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was Chief of Pediatrics at Family Health Plan in Salt Lake City, UT. He continues as a consultant for Shodair and is involved in publications with the group [Johnson et al., 1983; Pallister et al., 2011; Hudson et al., 2014]. Dr. Reynolds graduated from the University of Louisville School of Medicine and completed a pediatric residency at the University of Virginia in Charlottesville. He then trained in medical genetics under the mentorship of Dr. Thadeus Kelly at the University of Virginia. He joined the staff of Shodair Hospital directly from his fellowship. Dr. Reynolds served as the associate editor of the American Journal of Medical Genetics until John Opitz left, and Dr. Reynolds directed the Fetal Genetic Pathology program after his departure. He was the first author on the initial description of the cardio‐facio‐cutaneous syndrome [Reynolds et al., 1986]. During Dr. Johnson’s tenure at Shodair, the reach of regular genetics clinics expanded from west central Montana (Missoula) and south central Montana (Billings) to include southwest Montana (Bozeman, Butte), north central Montana (Great Falls), and northwest Montana (Kalispell). In order to meet the increased demand for genetic services, the number of genetic counselors more than doubled from two in 1994 to five in 2013 (Katherine Berry, Cindy Hudson, Tessa Pitman, Jaclyn Foster, Marissa Clark) (Fig. 2). The need for cancer genetic counseling born of advances in cancer genetics and genetic testing prompted the start of a counseling program for individuals at‐risk for a hereditary cancer syndrome. The program was overseen by Dr. Reynolds initially following the outreach model and more recently utilizing telemedicine.
The need for cancer genetic counseling born of advances in cancer genetics and genetic testing prompted the start of a counseling program for
individuals at‐risk for a hereditary cancer syndrome. Molecular cytogenetic techniques and routine fluorescent in situ hybridization (FISH) had been available at Shodair, but the molecular genetic diagnostic laboratory developed to its current state during Dr. Johnson’s tenure. Board‐certified in clinical and clinical molecular genetics, he oversaw the introduction of a broad range of molecular diagnostic assays covering neurodevelopmental, neurodegenerative, and growth disorders, as well as hereditary coagulopathies. With the current team of molecular genetics laboratory technicians, Katie Styren, Jon Schoof and Corbin Schwanke (Fig. 2), chromosomal microarray (CMA) and pharmacogenetic testing of drug metabolism were implemented. The Shodair molecular laboratory remains the only provider in Montana to offer constitutional CMA, ensuring timely access to what now is considered first‐tier genetic testing for children with developmental delays, autism spectrum disorders and congenital anomalies. Pharmacogenetics has since become an integral to the management of children treated in Shodair’s one acute and three residential child and adolescent psychiatric treatment units. The Medical Genetics Department has continued to play an important role in local and regional genetics education and training. As an official site for WWAMI of the University of Washington, a nationally and internationally recognized model for training physicians and other health professionals for rural areas, genetics staff are teaching third‐year medical students rotating through the genetics clinic. Through a collaboration with the University of Utah Graduate Program in Genetic Counseling, genetic counseling students participate in outreach genetic clinics during summer rotations. The Shodair laboratory also regularly hosts students from the University of Cincinnati, a connection established by former laboratory director Mary M. Haag, Ph.D. In addition, an educational program
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offers both local high school students and Helena’s Carroll College students unique opportunities to gain experience in the genetic laboratory. Initiated by John Opitz, the medical library maintains an extensive collection of medical journals, yearbooks and textbooks with primary focus on medical genetics, genomics and neuropsychiatric topics. A total of 63 genetics titles is currently available as print copies and online, many of which are unavailable elsewhere in Montana, underscoring the library’s role as a regional educational resource. In 2008, the State of Montana mandated expanded newborn screening to the 28 core conditions recommended by the American Academy of Pediatrics and American College of Medical Genetics in 2006. Until then, the newborn screening follow‐up had been coordinated by the clinical geneticists at Shodair supported by biochemical geneticists from the Universities of Oregon (Neil Buist) and Colorado (Janet Thomas). In response to the increased numbers of patients diagnosed with metabolic conditions neonatally, a comprehensive newborn screening follow‐ up program was established after the arrival of Samuel Yang, M.D. (Fig. 2), a board certified clinical and biochemical geneticist. He joined Shodair in 2010 after holding positions at Lanterman Developmental Center in Pomona, California, the Permanente Medical Group in San Francisco, Children’s Hospital of Los Angeles, and the California Department of Developmental Services. Dr. Yang is a graduate of Johns Hopkins School of Medicine. He trained in pediatrics at Stanford Medical Center and U.C. Davis Medical Center, followed by a fellowship in medical genetics at Children’s Hospital of Central California [Yang et al., 1997; South et al., 2010].
In 2008, the State of Montana mandated expanded newborn screening to the 28 core conditions recommended by the American Academy of
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Pediatrics and American College of Medical Genetics in 2006. The newborn screening follow‐up is coordinated and performed by an interdisciplinary team encompassing a biochemical geneticist, a metabolic dietician, a genetic counselor, a clinical psychologist, and a nurse coordinator. Patients and families are seen in metabolic clinics throughout the state including Missoula, Kalispell, Great Falls, Helena, Bozeman, and Billings. More recently, Dr. Abdallah Elias (Fig. 2) was involved as a consultant to the Department of Public Health and Human Services (DPHHS) in the development of administrative rule changes that allowed for the introduction of mandated neonatal screening for critical congenital heart disease (CCHD) by the State of Montana in 2014 (Fig. 1).
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CURRENT AND FUTURE DEVELOPMENTS Today, the medical genetics program at Shodair continues to have the strong support of its Board of Directors and Hospital Administrator of 27 years Jack Casey (Fig. 2), a trained laboratory technologist who was the genetics laboratory director back in 1970 and whose roots are deeply tied to Drs. Pallister and Opitz and the Montana Genetics Program. In 2012, Dongbin Xu, Ph.D. (Fig. 2), became director of the laboratory at Shodair Children’s Hospital after completing a fellowship in cytogenetics at The Children’s Hospital of Philadelphia (CHOP) where he was trained in clinical cytogenetics by Dr. Nancy Spinner and worked with Dr. Ian Krantz to establish a Drosophila model and an induced pluripotent stem cell model for investigating molecular genetic mechanisms underlying Cornelia de Lange syndrome [Xu and Krantz, 2012]. He earned his doctorate in biomedical science at the University of Texas
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M.D. Anderson Cancer Center at Houston. Born in China, Dr. Xu became a research assistant at Huazhong University of Science and Technology in Wuhan and graduate student at the Institute of Genetics in Fudan University at Shanghai, China before continuing his career in the United Sates. As a board‐certified clinical cytogeneticist with research experience in Drosophila genetics and stem cells, he brings to Shodair extensive experience in cytogenetic and molecular genetics. With particular interest in the cytogenetics and molecular cytogenetics of cancer, he and his staff (Karen Ellsworth, Joan Fitzgerald, Sandy Philips, Tammy Schwalbe, Mary Tunby, June Warner,and Amy Zearfos) (Fig. 2) offer a comprehensive panel for the diagnosis of hematologic cancers in addition to cytogenetic and molecular genetic tests for the diagnosis of a variety of hereditary genetic disorders. After 19 years at Shodair, Dr. Johnson moved to Boston, MA in 2013 where he became Chief of the Division of Genetics and Metabolism at
Figure 1. Map of Montana showing patients and their families (pink dots) by Montana City (red square). Shodair Children’s Hospital is located in Helena, Montana’s capital. Regular genetics clinics are held in Helena, Missoula, Kalispell, Great Falls, Bozeman, Butte, Billings. Periodic clinics are also held in Browning and Miles City.
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Figure 2. The Department of Medical Genetics, Shodair Children’s Hospital. Front row from left to right: Jaclyn Foster, Brittney Rio, Katie Styren, Tammy Schwalbe, Dongbin Xu, Sara Wakefield, Sandra Phillips, and June Warner; Back row from left to right: Katherine Grover, Samuel Yang, Tracy Wollett, Jonathan Shoof, Ellen Livers, José Camacho, Jack Casey, Abdallah Elias, Mary Tunby, Amy Zearfoss, Karen Ellsworth, Katherine Berry, and Cindy Hudson. Not in the photo: Corbin Schwanke and Marissa Clark.
Tufts Medical Center and a professor at Tufts University School of Medicine. After a tenure of 31 years at Shodair, Dr. Reynolds became interim‐director until his retirement in June 2014. A West Point graduate, Dr. Reynolds also retired from the U.S. Army as a brigadier general in 2006 after over 30 years of service and tours of duty in Vietnam, Boznia and Herzegovina, and Iraq. Abdallah F. Elias, M.D. (Fig. 2) joined the department in 2013 and became medical director of the Genetics Department at Shodair Children’s Hospital in June 2014. He is affiliate professor at the University of Montana, Department of Biomedical and Pharmaceutical Sciences and affiliate clinical faculty at the Western Montana Family Medicine Residency Program in Missoula, Montana, which is part of the WWAMI program. Dr. Elias completed a residency and fellowship in Clinical Genetics at the
McKusick‐Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine in Baltimore, MD. Under the mentorship of Dr. David Valle and Dr. Hal Dietz, he used genome‐wide approaches including genome‐wide linkage studies and next‐generation sequencing (NGS), to identify disease‐associated genetic variants in families with highly penetrant dominant familial thoracic aortic aneurysms/dissections. This contributed to the identification of loss‐of‐ function mutations in TGF beta 2 as a cause for syndromic familial aortic aneurysms [Lindsay et al., 2012]. Originally from Germany, Dr. Elias received his medical degree from the University of Freiburg in Germany and completed a pediatrics residency at the Children’s Hospital of the University of Freiburg in Germany, as well as training in Family Medicine at the University of South Dakota. He came to Montana initially as
a visiting scientist at the Rocky Mountain Laboratories, NIAID, NIH in Hamilton, MT, where Willi Burgdorfer had discovered the cause of Lyme disease in 1982 subsequently named after him. Elias demonstrated the feasibility of transforming infectious Borrelia burgdorferi in the laboratory of Patricia Rosa, laying the ground work for studying mutant bacteria in the experimental mouse‐tick infectious cycle [Elias et al., 2002]. José A. Camacho, M.D. (Fig. 2), who recently joined Shodair as a clinical geneticist, brings to the team a unique set of clinical and research experience. Prior appointments included positions in Pediatric Genetics and Metabolism at Miller Children’s Hospital in Long Beach, CA, Children’s Hospital of Orange County in Orange, CA, and the University of California, Irvine (UCI) Medical Center, where he also was an assistant professor. He has a special interest in
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mitochondrial disorders and was a faculty member at the Center for Molecular and Mitochondrial Medicine and Genetics (MAMMAG) and director of both the Mitochondrial Biochemical Diagnostics Laboratory and MITOMED, the clinical arm for MAMMAG at the UCI. He completed a fellowship in clinical genetics at the McKusick‐Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine in Baltimore, MD, where he also worked on molecular genetics of urea cycle disorders in Dr. Valle’s group. His work led to the identification of ORNT1 as the gene responsible for the hyperornithinemia‐ hyperammonemia‐homocitrullinuria (HHH) syndrome [Camacho et al., 1999]. After receiving his medical degree from the Universidad Central del Caribe (UCC) School of Medicine in San Juan, Puerto Rico, and completing a residency in pediatrics at the University of Missouri in Columbia, MO, he continued fellowship training in pediatric cardiology at Schneider’s Children’s Hospital of Long Island Jewish Medical Center and the University of Iowa, and was also a research scientist in the Department of Pharmacology of Columbia University College of Physicians and Surgeons. Coming to Shodair, Dr. Camacho brings an interest in translational approaches to integrate complex physiological and metabolic processes and genomic information to improve our understanding of complex diseases. As described in the preceding section, the Medical Genetics Department underwent important changes within the last few months and years prompted by both internal and external developments. These developments come at a time when the classic specialty of clinical genetics itself is undergoing a fundamental transformation. Increasingly, genomic approaches to the diagnosis of rare and common disorders are feasible in the clinical setting and are becoming accessible to a wider population. This is reflected not the least in the recent name change of ACMG to the American College of Medical Genetics and Genomics. Previously practicing predominantlyas diagnostic specialists, clinical geneticists are becoming involved in the management and care of patients across all
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age groups, often in close collaboration with other specialists and subspecialists. Examples of these developments are the involvement of geneticists in the management of individuals with neurodevelopmental, neuropsychiatric and neurodegenerative disorders, genetic epilepsies, and genetic‐ metabolic disorders for which targeted therapies are coming within reach. Such shifts have particular impact in the health care setting of Montana, which on the one hand is characterized by mostly rural communities, few urban centers separated by vast geographic spaces, high prevalence of underserved communities and low‐ income populations. On the other hand, Montana has a robust primary care based model of health care delivery which is constantly being enhanced by a growing number and diversification of specialists and sub‐specialists, allowing increasingly for the local management of patients with complex health problems.
These developments come at a time when the classic specialty of clinical genetics itself is undergoing a fundamental transformation. Increasingly, genomic approaches to the diagnosis of rare and common disorders are feasible in the clinical setting and are becoming accessible to a wider population. This is reflected not the least in the recent name change of ACMG to the American College of Medical Genetics and Genomics. It is in this context that the next generation of medical geneticists at Shodair is faced with the challenging responsibility of integrating genomic medicine in the diagnosis and care of their patients, reduce inequality of
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services within Montana and partner with colleagues across specialties to develop a more personalized practice of medicine (Fig. 2). One of the major developments at Shodair is the planned implementation of Next Generation Sequencing to allow for phenotype‐ driven analysis of genomic data early in the diagnostic process of complex disorders. In a setting where availability and geographic distances are impeding timely specialist evaluations, early phenotype/ genotype‐guided clinical evaluation— rather than exhaustive diagnostic odysseys preceding genetic testing—may be more cost efficient and improve patient care.
It is in this context that the next generation of medical geneticists at Shodair is faced with the challenging responsibility of integrating genomic medicine in the diagnosis and care of their patients, reduce inequality of services within Montana and partner with colleagues across specialties to develop a more personalized practice of medicine. Other developments and projects are being pursued at Shodair on several levels. The diagnosis and management of children with neurodevelopmental and neurobehavioral phenotypes were enhanced with the integration of formal neuropsychological evaluations by Dr. Christa Smelko, clinical psychologist, within the Medical Genetics Department. An increasing number of mitochondrial conditions have been identified and are being managed by the metabolic disorders team, and dedicated mitochondrial clinics are being implemented. Telemedicine, facilitated by several health telemedicine networks, has become an integral part in the delivery of genetic services within the
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Shodair model. Initially used for genetic counseling visits, its utility in assuring continuity of care and co‐managing patients with other providers is becoming increasingly recognized in the context of Montana’s challenging geography. In a similar development, the outreach of the department has recently further expanded by the addition of a genetic counselor at a satellite location in Kalispell, the regional health care hub of Northwestern Montana. The counselor not only coordinates and participates in on‐site and telemedicine genetic visits, but also is involved in outreach, needs assessment and education of underserved communities. Building on the foundation of its world‐renowned pioneers, the Montana Genetics Program is poised to flourish through ongoing support by the Montana Legislature, the Montana Department of Public Health and Human Services and the Shodair Foundation.
ACKNOWLEDGMENTS The author is grateful for the insight and knowledge gained from interviews with Jack Casey, John Johnson, Sandy Phil-
lips, Jim Reynolds, Dongbin Xu, Jose Camacho and Samuel Samuel Yang. Many individuals who were part of Shodair’s recent history remained unnamed and are hereby acknowledged.
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ARTICLE Chen Y, Myers L, Bjeda D, Oswald G, Elias AF, Levy HP, Anderlid BM, Yang MH, Bongers EM, Timmermans J, Braverman AC, Canham N, Mortier GR, Brunner HG, Byers PH, Van Eyk J, Van Laer L, Dietz HC, Loeys BL. 2012. Loss‐of‐function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nat Genet 44:922–927. Pallister PD, Pallister AB, South S, Toydemir R, Johnson JP, Beischel L, Opitz JM. 2011. A deletion 13q34/duplication 14q32.2‐14q32.33 syndrome diagnosed 50 years after neonatal presentation as infantile hypercalcemia. Am J Med Genet Part A 155A:833–839. Reynolds JF, Neri G, Herrmann JP, Blumberg B, Coldwell JG, Miles PV, Opitz JM. 1986. New multiple congenital anomalies/mental retardation syndrome with cardio‐facio‐ cutaneous involvement—The CFC syndrome. Am J Med Genet 25:413–427. South ST, Rector L, Aston E, Rowe L, Yang SP. 2010. Large clinically consequential imbalances detected at the breakpoints of apparently balanced and inherited chromosome rearrangements. J Mol Diagn 12: 725–729. Xu D, Krantz ID. 2012. Cohesin and human diseases. In: Ahituv N, editor. Regulatory sequences and human disease. New York: Springer. pp. 217–251. Yang SP, Bidichandani SI, Figuera LE, Juyal RC, Saxon PJ, Baldini A, Patel PI. 1997. Molecular analysis of deletion (17) (p11.2p11.2) in a family segregating a 17p paracentric inversion: Implications for carriers of paracentric inversions. Am J Hum Genet 60:1184–1193.
