Women are referred for prenatal (and less commonly preconception) genetic counseling and prenatal diagnosis for numerous reasons including advanced maternal age (>34 years), abnormal screening test results, abnormal ultrasound findings, family history of an inherited condition, consanguinity, teratogen exposure, and multiple miscarriages or stillbirths. Although all women are at risk to have a child with a chromosome abnormality, this risk increases with maternal age. Thus, advanced maternal age remains one of the most common reasons a woman is referred for prenatal genetic counseling. In 2007, the American College of Obstetrics and Gynecology (ACOG) recommended all women be offered first- and second-trimester maternal serum screening (MSS) for Down syndrome, trisomy 18, and open neural tube defects [5]. ACOG stated that women of all ages should have the option of invasive diagnostic testing. This is a large departure from when prenatal diagnosis was mainly offered to women 35 years and older in the 1970s and early 1980s.

Amniocentesis remains the most common prenatal diagnostic technique. The procedure involves guiding a needle through the abdominal wall into the uterus and withdrawing 20 cc of amniotic fluid, which contains fetal cells, for cytogenetic and molecular analysis. Optimally, amniocentesis is performed under ultrasound guidance between 14 and 18 weeks of gestation, but can be performed safely throughout the remainder of pregnancy as well. It has been reported to be associated with a fetal loss rate of 1 in 770 by experienced practitioners [6]. Another diagnostic procedure, called chorionic villus sampling (CVS), involves removal of a small amount of chorionic villi from the placenta, either transcervically or transabdominally, to obtain fetal cells for testing. Although the miscarriage risk associated with CVS is greater than that of amniocentesis at most centers, the advantage is that CVS can be performed in the first trimester of pregnancy at 10–13 weeks of gestation [7]. A new screening test for Down syndrome, performed by isolating cell-free fetal DNA in the maternal circulation, may significantly reduce the number of invasive diagnostic procedures performed. Early publications indicate the sensitivity of this maternal blood test for Down syndrome is >98 % with a specificity of 99.8 %, which compares highly favorably to traditional maternal serum screening for Down syndrome with a sensitivity of 60–93 % and specificity of 1–5 % [8].

Given the increasing sophistication of ultrasonography equipment and its routine use in pregnancy, most fetal anomalies such as neural tube defects, holoprosencephaly, abdominal wall defects, or severe cardiac abnormalities are detected prenatally and rarely present unexpectedly in the delivery room. Thus, prenatal genetic counselors often find themselves providing crisis counseling for individuals who have just been informed about a significant birth defect following a “routine ultrasound examination to confirm the pregnancy’s dates.” In fetal abnormality cases, when CVS or amniocentesis is performed, consideration is given to ordering comparative genomic hybridization (CGH) instead of just chromosome analysis since CGH can detect relatively small regions of deleted or duplicated genetic material compared with standard chromosome analysis [9].

Screening tests for single-gene disorders are recommended for expectant individuals or those planning a pregnancy in “high-risk ethnic groups” (see Table 3.2). The specific criteria used to select tests for population screening is based on a number of factors such as incidence in the population to be screened, medical knowledge of the disorder, and sensitivity and specificity of testing methods. In 2001, screening for cystic fibrosis (CF) was recommended but was controversial for the following three reasons: (1) the majority of expectant individuals would need to be offered screening; (2) the screening panel would not detect all carriers and would have variable detection rates depending on ethnicity; and (3) insufficient numbers of genetic counselors were available to provide informed consent [10]. Nevertheless, cystic fibrosis screening was successfully implemented by obstetricians and other primary care providers and couples who screened positive were referred to a genetic counselor.

In 2011, in dramatic divergence from ACOG and the American College of Medical Genetics (ACMG) testing guidelines, several direct to consumer marketing companies began promoting carrier screening tests for expectant couples for hundreds of exceedingly rare conditions, many of which were unfamiliar for most healthcare providers. Thus, providing proper informed consent for such prenatal panels was and remains difficult, at best. Furthermore, when a woman learns she is a carrier for a rare condition, a gene sequencing test may need to be offered to her reproductive partner since many of the mutations targeted on such panels represent a small percentage of the causative mutations for the specific condition. This may present two additional problems: (1) there may not be a clinical laboratory specifically performing sequence analysis for the rare genetic disorder in question, and (2) even if one succeeds in finding such a laboratory to perform sequencing, the reproductive partner may be found to have a variant of uncertain significance. This uncertainty may lead to confusion and high anxiety for a couple who thought that they were undergoing routine prenatal screening and would receive clear and clinically interpretable results.

Preimplantation genetic diagnosis (PGD) offers an alternative to prenatal testing for couples who are at risk of having a child with a genetic condition. Through in vitro fertilization (IVF), a single cell is removed from each embryo, usually on day 3 at the 8-cell stage, and tested for the specific genetic condition or familial mutation; then, the unaffected embryos are transferred back to the mother. PGD was first successfully performed in 1990 and is presently being offered for many monogenic disorders and chromosome abnormalities [11]. However, PGD is not yet routine as there are still many obstacles in the process related to the highly technical nature of the procedures and the difficulties in performing cytogenetic or molecular analysis on a single cell. The rate of pregnancy among patients undergoing IVF and PGD varies, but rarely exceeds about one third. Genetic counseling for couples considering PGD is imperative. Couples need to understand the risks and benefits of these complex procedures and the likelihood of a successful pregnancy. Couples need to weigh these factors against those of standard prenatal diagnosis procedures. IVF and PGD are very expensive, approximately $15,000 per cycle, and are not covered by most insurance providers.

Prenatal genetic counselors explain the risks for various genetic conditions, present patients with prenatal diagnostic testing choices, and discuss management and outcome options. They help patients make informed and autonomous choices by encouraging exploration of personal, spiritual, and cultural beliefs that affect decision making [12, 13]. Genetic counselors support patients who choose to continue affected pregnancies by arranging appointments with pediatric specialists, fetal and pediatric surgeons, and neonatal intensive care physicians to help the family prepare for the delivery and offer to arrange contact with other families who have had a baby with the same condition. Genetic counselors also support patients who choose to terminate affected pregnancies by making the necessary referrals for the procedure, encouraging autopsy when the diagnosis is still in question, and providing referrals to support groups for individuals who have had a therapeutic abortion.

Genetic conditions can occur with unique symptoms at all stages of life, from birth defects in a newborn to cognitive changes in an older adult. When a baby is born with birth defects or an individual at any age develops symptoms, the first step in clinical care is establishing an accurate diagnosis. Often medical geneticists are consulted by physicians caring for babies born with birth defects or other clinical symptoms to determine if there is one unifying syndrome or diagnosis that provides an explanation. Providing a diagnosis is helpful as it enables one to predict if the condition is associated with other problems that may develop over time, such as learning problems, behavioral disorders, cancers, or other medical conditions that are not present at the time of the examination. This may allow for early intervention, therapy and medical screening to reduce the impact of, or risk associated with, the conditions. Early diagnosis also may provide an explanation for likely causes of the condition and, therefore, potential recurrence risk for siblings or offspring of the affected individual. Up until 2010, chromosome analysis was a first line test in the evaluation of developmental disabilities, autism or multiple congenital anomalies. CGH should be the initial test for these conditions because the detection of causative deletions or duplications at 15–20 % is much higher than with chromosome analysis (3 %) [14].

Some individuals are affected with what appears to be a genetic condition, yet even after undergoing many tests, the diagnosis remains elusive. Exome sequencing has been conducted for such individuals on a research basis with a 25 % success rate in determining a diagnosis [15]. In 2012, exome sequencing also began to be offered on a clinical basis. Usually, in addition to sequencing the exome of the affected child, the exomes of the parents also are sequenced to determine if the child has de novo mutations or recessive mutations in the same gene from each parent. Analyzing such a large amount of data is very complex and requires an experienced bioinformatics specialist. Genetic counselors often are involved with developing the consent forms for exome sequencing as well as consenting the family members participating in exome sequencing research or clinical testing. Genetic counseling for exome sequencing is very time consuming because the genetic counselor, the patient, and their family members must consider what types of genetic variant information they are interested in learning about and are prepared to hear. For instance, in addition to the variants identified that may be causative for the disease in question, mutations predisposing to other conditions such as cancer, heart disease, and dementia may be detected.

When newborn screening for phenylketonuria was first available in the mid-1960s, the criteria developed to determine if a disorder should be considered for newborn screening included the following: (1) an acceptable treatment protocol is in place that changes the outcome for patients diagnosed early, (2) the condition’s natural history is understood, (3) there is an understanding about who will require treatment, and (4) testing is reliable for both affected and unaffected patients and is acceptable to the public [16]. Many states screened for only a few conditions up until the late 1990s when tandem mass spectrometry (MSMS) technology was developed for newborn screening; then the number of conditions screened expanded dramatically. Now, most states screen for at least the 29 rare, mostly metabolic, conditions recommended by ACMG in 2005 [17]. Many of the new conditions being screened do not satisfy all of the criteria originally used for inclusion in newborn screening protocols. Genetic counselors often coordinate, or are heavily involved with, state newborn screening programs and provide valuable information to pediatricians or other healthcare providers caring for newborns who have a positive screen for one or more of these rare disorders.