Genetic Counseling in Perinatal Medicine

Clinical genetics, a board-certified specialty, is now fully integrated into medical practice. Rapid advances in this field have been translated and transferred almost instantly, via the media, into the public domain. Not unexpectedly, the informed public (often prematurely) have developed immediate expectations of benefitting from these new developments. Hence, physicians are expected to be sufficiently well informed and up-to-date to provide or to refer for appropriate genetic counseling, evaluation, or laboratory testing. Certainly, genetic considerations are necessary in every family. Genetics has a role in virtually every disorder, in causation, predisposition and susceptibility, immune response, modulation, or reaction to medical treatment. It is estimated that each of us carries at least 20 harmful genes. About 1 in 13 conceptions results in a conceptus with a chromosome abnormality, 50 whereas about 50% of first-trimester spontaneous abortions are associated with such defects. 7 Clinically significant chromosomal defects occur in 0.65% of all births, an additional 0.2% being born with balanced structural chromosome rearrangements that have implications for reproduction later in life. Between 5.6% and 11.5% of stillbirths and neonatal deaths are associated with chromosome defects. 2 Three percent to four percent of all births are associated with a major congenital malformation, mental retardation, or genetic disorder, a rate that doubles by 7 to 8 years of age, given later-appearing or later-diagnosed genetic disorders. 44 Genetic counseling is a communication process concerning the occurrence and the risks of recurrence of genetic disorders within a family. Such counseling aims to provide the patient with a clear and comprehensive understanding of all the important implications and possible options of the disorder in question, to facilitate rational decision making. 44 The basis and guidelines for genetic counseling have been extensively reviewed and are not covered here. 43 , 44 Indications for genetic counseling are summarized below: 1 Advanced maternal age 2 Abnormal maternal serum triple screen 3 Abnormal ultrasound evaluation during pregnancy 4 A previous fetus or child with a genetic disorder or congenital defect 5 Parent with a genetic disorder 6 Family history of a specific genetic disorder 7 A maternal disorder with or without specific drug treatment associated with an increased risk of congenital defects 8 A maternal disorder in which pregnancy could threaten maternal or fetal life or health 9 Known or possible carriers of specific harmful genes (including ethnic-related disorders) 10 Exposure to teratogenic drugs, infections, x-rays, toxins, or occupational hazards during or before pregnancy 11 Known or suspected consanguinity 12 Consideration of presymptomatic/predictive laboratory testing Preconception care and counseling, with appropriate anticipatory guidance, is important in the identification of risk factors, disease states, and potential teratogens, and prompts the offering of carrier and prenatal diagnostic testing. The availability of first-trimester prenatal diagnosis and the advent of presymptomatic diagnosis by DNA analysis has created increasing opportunities to avoid disorders characterized by early death, severe disease, or irreparable mental retardation. Periconceptional maternal folic acid supplementation has now been shown conclusively to provide a high protective effect against neural tube defects. 38 , 41 Certain maternal disease states, including diabetes, lupus, and myotonic muscular dystrophy, impose their own specific potential maternal, fetal, neonatal, and other complications. So far as pregnancy and fetal defects are concerned, the preconception visit provides important opportunities for intervention, avoidance, or prevention. The patients' ethnicity and medical and genetic family history are key elements in this evaluation. Patients with prolonged infertility of unknown cause or recurrent spontaneous abortion, who may have a 3% to 10% risk of a parental chromosome abnormality, 55 , 60 require chromosome analysis, as do their spouses. Virtually all ethnic groups carry some “genetic burden.” 40 For example, whites have a risk of about 1 in 25 for carrying the gene for cystic fibrosis (CF). Ashkenazi Jews have a risk of about 1 in 30 for carrying the gene for Tay-Sachs disease and a risk of about 1 in 12 for carrying the gene for Gaucher's disease. DNA testing for carrier states are now readily available at major diagnostic centers. These relatively inexpensive and accurate tests enable more precise genetic counseling, information that becomes important for those who might select prenatal diagnosis as an option, or for couples who prefer to avoid the possibilities of abortion and prefer artificial insemination from a donor known not to carry that specific gene. In the future, preimplantation diagnosis may require discussion during the preconception visit, because technically this now is a reality. With the traditional modes of inheritance come several nontraditional modes and mechanisms of inheritance that often pose complex issues in genetic counseling.