Bridging the gap between gene discovery and our ability to use genetic information to benefit health requires population-based knowledge about the contribution of common gene variants and gene-environment interactions to the risk of disease. The risks and benefits associated with population-based research involving genetics, especially lower-penetrance gene variants, can differ in nature from those associated with family-based research. In response to the urgent need for appropriate guidelines, the Centers for Disease Control and Prevention formed a multidisciplinary group to develop an informed consent approach for integrating genetic variation into population-based research. The group used expert opinion and federal regulations, the National Bioethics Advisory Commission's report on research involving human biological materials, existing consent forms, and literature on informed consent to create suggested language for informed consent documents and a supplemental brochure. This language reflects the premise that the probability and magnitude of harm, as well as possible personal benefits, are directly related to the meaning of the results for the health of the participant and that appropriate disclosures and processes for obtaining consent should be based on an assessment at the outset of the likelihood that the results will generate information that could lead directly to an evidence-based intervention. This informed consent approach is proposed to promote discussion about how best to enable potential participants to make informed decisions about population-based research involving genetics and to suggest issues for consideration by research sponsors, institutional review boards, and investigators.

ESHG background document genetic testing and common disorders F Becker et al S10 European Journal of Human Genetics Knowledge of test Feasibility of screening procedures Suitable test or examination. Suitable test or examination. Test acceptable to the population. Entire screening procedure acceptable to the population. Case finding should be a continuing process and not 'once and for all' project. Screening should be a continuing process and should encompass all elements of screening procedures. Treatment for disease Interventions and follow-up Accepted treatment for patients with recognized disease. Interventions that have physical, psychological, and social net benefit available. Facilities for diagnosis and treatment available. Facilities for adequate surveillance, prevention, treatment, education, counselling, and social support available. Agreed on policy concerning whom to treat as patients. Consensus on accepted management for those with positive test results. Cost considerations Societal and health system issues Costs of case finding (including diagnosis and treatment of patients diagnosed) economically balanced in relation to possible expenditures on medical care as a whole. Costs should be balanced in economic, psychological, social, and medical terms and with health-care expenditures as a whole. Appropriate screening services accessible to the entire population, without adverse consequences for non-participants. Appropriate confidentiality procedures and antidiscrimination provisions for participants and non-participants. a Ethical, legal, and sociobehavioral issues are considered across all domains. Screening should be considered within a framework that recognizes fundamental human rights.

The birth prevalence of congenital anomalies in developing countries is similar to that observed in developed countries. However, the health impact of birth defects is higher because of a lack of adequate services for the care of affected infants and a higher rate of exposures to infections and malnutrition. A number of successful measures for the prevention of congenital anomalies are being taken in a number of developing nations. Primary prevention programs are based on public education about preconceptional and prenatal risks. Prevention based on reproduction options includes teratogen information services and prenatal screening for fetal anomalies. In addition, programs for the detection of congenital malformations at birth, followed by early treatment, are contributing to secondary prevention. Prevention of congenital anomalies in the developing world requires: (a) good epidemiological data on the prevalence and types of birth defects and genetic disorders; (b) educating health professionals in the goals and methods of preventing birth defects at low cost but with high impact, and (c) expansion of family planning and improvement of antenatal care combined with educational campaigns to avoid the risks for birth defects. The basis for public health preventive measures should be the primary health care level. In a sizable proportion of developing countries, the stage is already set for these measures to be implemented. Required are education, political will, and proper organization and allocation of resources.

We report on a 46,XY newborn infant with Smith-Lemli-Opitz (SLO) syndrome with female external genitalia, intraabdominal testes with epididymides and deferent ducts and a normally shaped uterus and vagina. Polydactyly, cleft palate, and several internal organ malformations were also present, and the patient died shortly after birth. Data on six reported male infants with SLO syndrome and female external genitalia suggest a correlation between degree of genital involvement and overall degree of severity. Scoring systems to quantify overall degree of severity (SLO score) and degree of genital involvement in males (genital score) were devised and applied to 122 reported cases from the literature. Statistical analyses showed a unimodal distribution of the SLO severity scores, and positive correlations between the SLO score and the genital score in males, the presence of polydactyly, and the presence of cleft palate. In 19 multiplex families the affected sibs were generally similar in their SLO scores. The above analyses suggest that the wide phenotypic variability in the SLO syndrome is determined by variable expressivity of the same entity as opposed to genetic heterogeneity. The observed phenotypic correlations naturally determine that males with complete feminization are among the more severe patients and tend to have polydactyly and cleft palate.

Close to 12% (33 million) of the U.S. population is of Latino ethnocultural background, and it is estimated by the year 2005 they will become the largest ethnic minority. This article describes the demographic, social, economic, and cultural characteristics of the Latino population in the United States. Main health problems of Latinos and barriers to access to equitable health care are described. Health beliefs of relevance in the provision of health care in general, and of genetic counseling in particular, are reviewed. Some key nuances of genetic counseling to Latinos are discussed, such as the problems of language and other pitfalls in communication, the role of nondirectiveness in Latino culture, the medicalization of pregnancy, the language of prospective risks, and the meaning of disability. To provide culturally appropriate genetic counseling to Latinos, genetic professionals must be conversant with their personal and social history, culture, and traditions. At the same time, cultural stereotyping must be avoided, as the individuality of each patient must be recognized, acknowledged and respected.

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The IVIC syndrome is an autosomal dominant condition affecting mainly the upper limbs. It is described from 19 living members of one family of mostly Caucasoid descent; it came to Venezuela from the Canary Islands 140 years ago. The new mutation appeared six generations ago. It has complete penetrance and wide expressivity for a radial ray defect which may vary from an almost normal thumb to a severely malformed upper limb. When present, the thumb has a long/slender metacarpal and a short distal phalanx, reflected in a typical metacarpophalangeal (MP) pattern profile. Anthropometry reveals delayed growth in the forearms, clavicles, and cranium during adolescence, and permanently in the spine; the maturation of the face, tibiae, and feet is normal. The radial carpal bones are always affected, some being still hypoplastic at advanced ages. Constant palmar dermatoglyphic anomalies are a high a-b ridge count, a distally placed or absent t triradius, and an increased frequency of patterns in the second interdigital area. Extraocular muscles are involved almost always, producing strabismus. Hearing is bilaterally impaired due to a mixed congenital loss, either total or partial. Mild thrombocytopenia and leukocytosis are present before the age of 50 years. There is neither associated ectodermal dysplasia nor heart involvement [except for occasional mild, incomplete right bundle branch block (IRBBB)]; imperforate anus occurs in about 10% of affected persons. The possible pathogenetic relationship to the thalidomide embryopathy and to the Holt-Oram syndrome, among others, is discussed.