Editorial Community Genet 2002;5:5–7
From Knowledge to Implementation M.C. Cornel Clinical Genetics and Human Genetics, VU University Medical Center, Amsterdam, The Netherlands
Key Words Congenital anomalies W Genetic diseases W Prevention W Policy W Implementation
Every year some 3–9 million infants (2–6% of newborns) are born worldwide with major congenital anomalies and genetic diseases, many of which have severe health effects [1]. In countries where the mortality and morbidity caused by infectious diseases and malnutrition have been reduced, congenital and genetic diseases have now been recognized as an important field for health improvement. Depending on the ways of ascertainment, congenital anomalies, apparent during pregnancy, at birth or during the first weeks of life, are registered in 1–4% of infants [2, 3]. The higher percentages are reported in areas with high ascertainment, for instance where all newborns are examined by pediatricians, and include more mild anomalies. After the first week of life, many congenital anomalies that are hard to diagnose at birth are still detected among which congenital cardiovascular anomalies in around 0.5% [2] and mental retardation in roughly 1% [4]. Monogenetic diseases are often not counted as congenital anomalies and not recognized at birth. However, they affect another 2.4% of people, a figure that was recently upward revised (from 1.25%, used until the early 1990’s) [5]. Clearly congenital anomalies, including genetic diseases, affect many infants and their parents and families, and if primary prevention would be possible, much suffering could be avoided. The aim of Community Genetics is to maximize the benefits of medical genetics for
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the community, while minimizing any threat or harm [6]. In this special issue of Community Genetics we will pay attention to primary prevention of congenital anomalies. In this field, the operationalization of the aim of Community Genetics can be the activities to identify etiological factors of these anomalies and to implement this knowledge, so that future generations can benefit from the knowledge acquired. A classical example in this field is rubella infection during pregnancy, which appeared to cause birth defects of heart, eye and ear: congenital rubella syndrome. Vaccination programs are now carried out in many countries, and congenital rubella syndrome is rare in western countries. The circulation of the virus is limited and many pregnant women were vaccinated in childhood. Obviously, we need to stay alert because new opportunities for prevention may become available. Recent migrants to western countries appear to be a high risk group which can easily be vaccinated [7, 8]. Furthermore, in southern countries congenital rubella syndrome still may cause embryopathy in numerous children, and rubella immunization should be considered [9]. For syphilis, adequate knowledge is also available, and prevention of congenital syphilis appears to be possible. However, both in western countries and in developing countries, efforts to improve prevention strategies should continue, paying attention to testing early in pregnancy, availability of quick test result and rapid treatment [10– 12]. Other classic examples are teratogenic drugs, such as thalidomide and retinoids [13, 14]. Now that we know
M.C. Cornel, MD, PhD Clinical Genetics and Human Genetics, VU University Medical Center Polikliniekgebouw, receptie D, PO Box 7057 NL–1007 MB Amsterdam (The Netherlands) Tel. +31 20 444 0051, Fax +31 20 444 0769, E-Mail
[email protected]
that certain drugs can cause severe birth defects, we are obliged to avoid exposure during pregnancy as much as possible. Why do I mention congenital rubella syndrome, congenital syphilis and teratogenic drugs in a journal devoted to community genetics? It is not always clear to everybody that geneticists are involved in more than inherited disease. For clarification, it may help to study the policy documents of highly specialized clinicians in genetics [15]. Clinical genetics is concerned, amongst other issues, with the evaluation of children and adults with mental retardation, birth defects, congenital malformations, chromosomal abnormalities, neurologic and muscular problems [15]. The core tenet of clinical genetics is that establishing a specific and accurate diagnosis confers significant benefit to the patient and family [15]. If a couple visits the clinical geneticist for the first time because their child has severe health problem, the etiology of the problem is often unknown. In order to establish a specific diagnosis, clinical geneticists need knowledge of genetics, but also of teratology. Not only would they inform parents about increased recurrence risks in case of monogenic disorders, but the response to the question ‘Will it happen again? might as well be: ‘It is highly unlikely’, for instance in cases of congenital rubella syndrome. For multifactorial disorders, quantitatively even more important than monogenic disorders, the etiology is partly genetic and partly environmental. Parents who lost a child due to spina bifida, for instance, will be told that in order to reduce the recurrence risk, they should take 5 mg of folic acid daily (a high dosage) from 1 month before conception until 3 months thereafter, in order to reduce their recurrence risk from a few percents (depending on the population) to less than one percent. Thus knowledge of environmental factors in the etiology of congenital anomalies is part of the professional background of geneticists. In this issue, two publications will focus on the question how to identify new etiological factors for congenital anomalies [16, 17]. For maternal diabetes mellitus and epilepsy, our knowledge of risks can help to optimize treatment before and during pregnancy, and thus reduce risks as much as possible [18, 19]. Informing the public and implementation in health care of a broader field of knowledge on prevention of congenital anomalies is a more complex issue, discussed in this issue for developing countries [20], as well as western countries [21]. A major opportunity for preventing congenital anomalies is an increase in the intake of folic acid around the time of conception, which reduces the risk of neural tube defects and other congenital anomalies [22]. Although the scientific
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evidence is conclusive, governments are not taking their responsibility and thus let the pandemic of folic acidpreventable spina bifida and anencephaly continue, as Dr. Godfrey Oakley explains in his evocative review [22]. For many potential risk factors, knowledge is limited, and current policy has to be based on available but incomplete knowledge. This is illustrated for physical and chemical factors in the home and at work [23]. Due to the current developments in genomics, proteomics and metabolomics, one can expect new insights into the etiology of congenital anomalies. Now that the entire genome has been sequenced, those insights will increasingly concern pathways from genes via protein function and (concentrations of) metabolites to diseases and symptoms. Treatments of diseases may be thought of as interventions in these pathways. On the other hand, for congenital anomalies of multifactorial etiology, changes in the environment of the developing fetus (increased intake of folic acid, reduction of exposure to cigarette smoke and alcohol) may as well be thought of as interventions in these pathways. For the prevention of the occurrence of multifactorial diseases, lifestyle changes will increasingly become part of what genetics is all about [1]. The current issue illustrates that the implementation of knowledge of the etiology of congenital anomalies is a major challenge, not only for geneticists, but also for public health experts, physicians in many other fields, and governments.
Cornel
References 1 Boulyjenkov V: WHO Human Genetics Programme: A brief overview. Community Genet 1998;1:57–60. 2 EUROCAT Working Group (ed): Fifteen Years of Surveillance of Congenital Anomalies in Europe 1980–1994. EUROCAT Report 7 with Addendum. Brussels, Scientific Institute of Public Health, 1997. 3 International Clearinghouse for Birth Defects Monitoring Systems: Annual Report 2001. Rome, The International Centre for Birth Defects, 2001. 4 Roeleveld N, Zielhuis GA, Gabreels F: The prevalence of mental retardation: A critical review of recent literature. Dev Med Child Neurol 1997;39:123–132. 5 Sankaranarayanan K: Estimation of the hereditary risks of exposure to ionizing radiation. History, current status, and emerging perspectives. Health Phys 2001;80:363–369. 6 Henneman L, Langendam MW, Ten Kate LP: Community Genetics and its evaluation: A European Science Foundation Workshop. Community Genet 2001;4:56–59. 7 Reef SE, Frey TK, Theall K, Abernathy E, Burnett CL, Icenogle J, McCauley MM, Wharton M: The changing epidemiology of rubella in the 1990s: On the verge of elimination and new challenges for control and prevention. JAMA 2002;287:464–472. 8 Sheridan E, Aitken C, Jeffries D, Hird M, Thayalasekaran P: Congenital rubella syndrome: A risk in immigrant populations. Lancet 2002;359:674–675.
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9 Christianson AL, Gericke GS, Venter PA, Du Toit JL: Genetics, primary health care and the Third World. S Afr Med J 1995;85:6–7. 10 Beksinska ME, Mullick S, Kunene B, Rees H, Deperthes B: A case study of antenatal syphilis screening in South Africa: Successes and challenges. Sex Transm Dis 2002;29:32–37. 11 Warner L, Rochat RW, Fichtner RR, Stoll BJ, Nathan L, Toomey KE: Missed opportunities for congenital syphilis prevention in an urban southeastern hospital. Sex Transm Dis 2001; 28:92–98. 12 Gust DA, Levine WC, St Louis ME, Braxton J, Berman SM: Mortality associated with congenital syphilis in the United States, 1992–1998. Pediatrics 2002;109:E79. 13 Castilla EE, Ashton-Prolla P, Barreda-Mejia E, Brunoni D, Cavalcanti DP, Correa-Neto J, Delgadillo JL, Dutra MG, Felix T, Giraldo A, Juarez N, Lopez-Camelo JS, Nazer J, Orioli IM, Paz JE, Pessoto MA, Pina-Neto JM, Quadrelli R, Rittler M, Rueda S, Saltos M, Sanchez O, Schuler L: Thalidomide, a current teratogen in South America. Teratology 1996;54:273– 277. 14 Mitchell AA, Van Bennekom CM, Louik C: A pregnancy-prevention program in women of childbearing age receiving isotretinoin. N Engl J Med 1995;333:101–106.
15 Williams MS: Genetics and managed care: Policy statement of the American College of Medical Genetics. Genet Med 2001;3:430–435. 16 Clementi M, Di Gianantonio E, Ornoy A: Teratology information services in Europe and their contribution to the prevention of congenital anomalies. Community Genet 2002;1:8– 12. 17 Reefhuis J, de Jong-van den Berg LTW, Cornel MC: The use of birth defect registries for etiologic research: A review. Community Genet 2002;1:13–32. 18 McLeod L, Ray JG: Prevention and detection of diabetic embryopathy. Community Genet 2002;1:33–39. 19 Ten Berg K, Lindhout D: Antiepileptic drugs in pregnancy: Options for the prevention of congenital abnormalities. Community Genet 2002;1:40–49. 20 Penchaszadeh VB: Preventing congenital anomalies in developing countries. Community Genet 2002;1:61–69. 21 De Weerd S, Steegers EAP: The past and present practices and continuing controversies of preconception care. Community Genet 2002;1:50–60. 22 Oakley GP: Global prevention of all folic acidpreventable spina bifida and anencephaly by 2010. Community Genet 2002;1:70–77. 23 Robert-Gnansia E, Saillenfait AM: Physical and chemical factors in the home and workplace during pregnancy. Community Genet 2002;1:78–85.
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