Genetic counseling: Family history interpretation and risk assessment

INTRODUCTION — The process of genetic counseling is about sharing information regarding genetic and disease risks in a manner useful to an individual, couple, or family. It involves obtaining the family and medical history from the patient and referring clinician, obtaining and reviewing medical records of the patient and family members, including genetic testing results, understanding the patient's perception of risk of developing a condition or recurrence of a condition, advising the patient about the availability of and advantages and disadvantages of genetic testing, assisting in choosing the most appropriate genetic test(s), and determining the implications of genetic test results and possible interventions for risk reduction, all in the context of the value system most relevant to the patient and family.

This topic provides guidelines for genetic counseling, including interpretation of the family history and assessment of risk for common adult-onset conditions.

Additional discussions about genetic testing, use of genetic information to guide drug dosing (pharmacogenomics), disclosure of incidental findings from genetic testing, and a glossary of genetics terminology are provided on the following reviews:

●Genetic testing – (See "Genetic testing".)

●Pharmacogenomics – (See "Overview of pharmacogenomics".)

●Personalized medicine, including direct-to-consumer testing – (See "Personalized medicine".)

●Disclosure of incidental findings from genetic testing – (See "Secondary findings from genetic testing".)

●Genetics terminology – (See "Genetics: Glossary of terms".)

DEFINITION OF GENETIC COUNSELING — As defined by the National Society of Genetic Counselors, genetic counseling is the process of helping people understand and adapt to the medical, psychological, and familial implications of genetic contributions to disease [1]. This process integrates:

●Collection of a detailed family history; interpretation of the family history with the medical history to assess the chance of disease occurrence or recurrence

●Education of the patient (and family) regarding the inheritance, testing, management, risk reduction, available resources and research regarding the condition

●Counseling to promote informed choices and appropriate interventions

Information used in genetic counseling may come from the patient, family members, referring clinician, medical record, and test results from other sources. The patient's desire, ability, and willingness to obtain more information are also important especially if medical records or test results from other family members are important to risk assessment. Genetic risk assessment is most accurate using confirmed family history information. According to the health belief model, the patient's perception of risk also influences the behavior; patients who have a perceived higher risk may be more enthusiastic about researching than those who do not perceive an increased risk. The genetic counselor or clinical geneticist uses family and personal medical history to formulate a diagnosis or risk assessment. Genetic counseling also includes providing information about strategies to modify the risk, including the possibility of genetic testing, and ways to incorporate the information as it pertains to medical management, emotional response, and family dynamics.

Genetic counseling can be conducted at any time along a life spectrum, from pre-conception to old age. This includes pre-conception and prenatal counseling about the potential health of a baby, genetic evaluation of a neonate with congenital anomalies or a toddler with developmental delay. Some inherited conditions are present at birth, while others do not manifest until adolescence or adulthood. While some genetic diseases are well-recognized as occurring later in life (eg, Huntington disease), in the last few decades, discovery of genes implicated in common adult-onset conditions such as heart disease, movement disorders, and cancer have increased the role of genetic counseling for risk assessment in adults.

Most genetic services are provided as outpatient consultations to the primary care provider and/or appropriate specialist, such as the neurologist, cardiologist, or oncologist (for familial adult-onset syndromes), or obstetrician (for preconception or prenatal counseling). Typically, patients will be referred back to their physicians with recommendations for their follow-up care. However, some specialist clinics will continue to follow patients at regular intervals, especially in pediatrics. This is particularly important for metabolic conditions, in which lifelong dietary interventions or medications are required.

INDICATIONS FOR REFERRAL — The indications for genetic counseling are increasing as genetic and genomic testing becomes more accurate and affordable and as more interventions to reduce disease risk become available. If the personal or family history includes a confirmed clinical diagnosis with a known genetic etiology such as hemophilia, neurofibromatosis, or Marfan syndrome, a referral may be appropriate if the patient has questions about inheritance patterns or risk to self.

Genetic counseling may be linked with genetic testing (either in offering appropriate testing or interpreting results of testing), but it also may be an integral part of patient care in the absence of genetic testing. In some cases, risk assessment and counseling may be helpful in determining that testing is not needed. Engaging genetic counselors and/or clinical geneticists can be extremely valuable in navigating these issues.

Primary care providers should be comfortable initiating the process by obtaining an initial family history (see 'Family history' below and 'Information to send with the referral' below), categorizing the likely genetic risk for the individual (see 'Increased risk' below), and assisting in identifying an appropriate genetics professional. (See 'Where to refer' below.)

Increased risk — An initial family history includes assessment of genetic conditions in first-, second-, and third-degree relatives. The degrees of relatedness and the contributions to genetic risk are listed in the table (table 1) and illustrated in the family pedigree schematic (figure 1). Once the family history is obtained, the individual's level of risk can be categorized as average, moderate, or high for most adult-onset conditions (table 2) [2].

●Individuals presenting with strong family histories for conditions with a known genetic basis (those considered high risk) should be offered a referral to a clinical geneticist or genetic counselor. These individuals may have a significantly greater lifetime risk for developing the disease, and disease onset may occur earlier than would be detected by general population screening guidelines (such as for cancer, neurodegenerative disorder, or cardiovascular condition). An important implication for management is the need for increased screening or screening initiation at an earlier age. (See 'Risk modification' below.)

●Individuals at moderate risk may not require counseling unless there are unusual circumstances (eg, status of family members not available). These individuals often have a two- to threefold increased risk for disease. However, some of these individuals may be offered more intensive screening than is recommended for those in the general population. As an example, a patient whose father had colon cancer at age 55 would fall into the moderate risk category, with an estimated twofold increased risk for colon cancer [3,4]. Colonoscopy for this patient would be recommended at age 40 rather than the usual 50 years of age. (See "Screening for colorectal cancer in patients with a family history of colorectal cancer or advanced polyp".)

●Individuals at relatively low risk for an inherited condition may still meet criteria for genetic testing, often when therapeutic options are available for individuals with certain genotype and the results of genetic testing will impact treatment decisions. For example, the National Comprehensive Cancer Network (NCCN) recommends genetic testing for every male with metastatic prostate cancer, regardless of family history [5]. Some of these individuals may meet with a genetics professional prior to genetic testing.

The distribution among risk categories depends on the patient population. Among 200 pedigrees from patients seen in a prenatal clinic, 1 to 10 percent were classified as high risk for at least one common adult condition, and 5 to 15 percent were classified as moderate risk [2]. Similar prevalence of high-risk patients has been reported in other studies [6]. Although high- and moderate-risk patients account for only a small portion of the patient population, these kindreds represent a significant proportion of the disease burden. As an example, a study in Utah found that while only 14 percent of the population had a positive family history for coronary heart disease (CHD), these kindreds accounted for 48 percent of all the CHD in the state and for 72 percent of all early onset CHD [7].

Despite the appropriateness of referral for genetic counseling of high-risk individuals, these referrals often are not made. This was illustrated in a 2015 survey of 5558 women from a tumor registry who had breast, ovarian, or endometrial cancer, of whom 820 were identified as candidates for genetic counseling referral based on National Comprehensive Cancer Network (NCCN) guidelines [8]. Of these, only 178 (22 percent), were referred for genetic counseling. Barriers to referral may include a perceived lack of benefit, uncertainty about the implications, lack of awareness of available tests or genetics professionals, patient fear or reluctance to undergo testing, and/or cost and reimbursement issues [9].

Uncertainty about genetic basis — For many common adult-onset conditions such as diabetes, cancer, heart disease, and certain neurologic conditions, clinicians may be uncertain whether there is sufficient information about the genetic etiology for a referral to be useful. The lack of sufficient information to inform the evaluation will be especially true if the family size is small and the age at which the condition developed is younger than average; many conditions with a genetic etiology will have a younger age of presentation compared with that typically seen in the general population. The rapid rate of gene discovery following the mapping of the genome and the advent of genome-wide association studies and genomic sequencing has exponentially increased the information available, making it challenging to stay informed. Genetic counseling may be appropriate to address this uncertainty, especially if the individual providing the counseling has specific expertise in the condition in question.

In addition, there may be opportunities to participate in ongoing research protocols that may result in new discoveries:

●Research or registry opportunities may exist that may allow early access to new genetic information and medical management or prevention opportunities for identified individuals or families [10]

●Some families may choose to bank DNA for the possibility of future genetic testing even if a research registry is not available

Patient anxiety or misunderstanding about risk — Patient anxiety about a family member's condition or misunderstanding of risk may raise additional questions and/or concerns. For individuals or families with anxiety or misunderstanding about genetic risk, a genetic counseling consultation can provide education and counseling to help the individual understand and cope with risk information and make management decisions [11].

However, it is important to note that not everyone with a concern about genetic etiology of disease in themselves or family members will meet criteria to be further evaluated by a genetic professional.

PREPARATION FOR REFERRAL — A discussion between the referring clinician and the patient is essential to prepare the patient and make the counseling appointment as useful as possible. This may include a review of the features of the family history that prompted the referral and the likely content of the counseling visit [12]. Clarifying the patient's concerns and distinguishing them from the provider's concerns increases the productivity of the referral and follow-up communications. As an example, if a provider is interested in genetic testing, but no relevant genes are yet associated with the clinical presentation in the patient or family and there are no management changes regardless of the testing, the visit may be perceived as unnecessary by the patient. The National Society of Genetic Counselors has created a resource for patients who have questions about the genetic referral and how to prepare (http://aboutgeneticcounselors.com/).

The practical aspects of the referral also need to be evaluated. Historically, genetic counseling has been associated with universities and major medical centers, although community hospitals are often including the service as well. In addition, companies that offer counseling using telehealth services (eg, telephone, videoconferencing) are becoming more common, making access to genetic counseling easier. During the COVID-19 pandemic, many health care institutions have expanded telehealth genetic counseling services, which may further expand options for patients. More insurance companies are requiring that genetic counseling precede genetic testing, usually from an entity other than the laboratory, and as a result, many insurance companies authorize coverage, although plans vary and it is important to have the patient check with the specific plan.

Information to send with the referral — Referring clinicians make the initial assessment of the patient's family history and potential risk of genetic disease to determine the need for a genetic counseling referral [13]. Once a decision is made to refer a patient to a clinical geneticist or genetic counselor, the referring clinician should provide the following information to the consultant:

●At minimum, the referral should be accompanied by the specific question to be addressed by the referral. It is more useful to ask the counselor to "please evaluate to identify test or screening appropriate for family history of both thyroid and early onset breast cancer" than it is to state "breast cancer."

●It is helpful for the referral to be accompanied by available family history information, including affected family members, their relationship to the patient, and their age at diagnosis. (See 'Family/medical history from the referring clinician' below.)

●A summary of the patient's pertinent medical history, including relevant laboratory test results and/or biopsy reports.

●Information if genetic testing has been performed on a family member (and the result, if known).

Family/medical history from the referring clinician — The clinician initiating the referral must obtain a family history that is sufficient to establish whether referral is appropriate. Generally, this involves collection of potentially relevant information limited to first-degree relatives (parents, siblings, children) and second-degree relatives (eg, grandparents, aunts, uncles, grandchildren, half-siblings); third-degree relatives may also be included. These categories of relatedness are listed in the table (table 1) and illustrated in the schematic (figure 1).

Key questions to ask in obtaining a family history relate to patient concerns about disease, problems with pregnancy, occurrence of congenital anomalies, early deaths or disease onset, and determination of nongenetic risk factors for disease. Additional questions related to family size (eg, "How many brothers and sisters do you have?"; "Do you come from a large family?") are often helpful in interpreting the responses to the screening questions. Assessment of consanguinity, in which parents share a common ancestor, can also be helpful for determining the risk for an autosomal recessive condition. Patients may be unaware of precise medical diagnoses in family members, but can provide revealing information regarding symptoms, surgeries, and medication use. Patients may neglect to mention the medical conditions of siblings or other relatives who have died (often the most informative information). Direct questions addressing these issues are also helpful.

While there are advantages to using a family health history, several barriers still exist for providers, patients, and medical record systems in general [14-16]. One study in community family medicine practices found that family histories were only discussed in 51 percent of new patient visits and 22 percent of follow-up visits [17]. A study that surveyed community health center patients concluded that those who were more likely to talk with doctors as well as family members about their family health history were more likely to report a history of cancer or heart disease, opening the opportunity for clinicians to obtain a more comprehensive family history [18]. However, even when the family history is discussed, the level of detail and documentation of the history are often insufficient for making adequate risk assessments [6,19,20].

In some situations, such as an early onset presentation of an adult-onset condition, a genetic consultation may be warranted even if there is no relevant family history [21].

●Small family size or underrepresentation of one sex may limit the ability to recognize patterns in the pedigree. As an example, small families or families with few females may fail to exhibit a strong pattern of breast and ovarian cancer even if a genetic mutation in BRCA1 or BRCA2 is present [21].

●Uncertainty in parentage (or incorrect attribution of parentage) may render a pedigree inaccurate. Population-based studies have found that up to 15 percent of individuals may misidentify parentage [22]. In other situations, such as adoption or estrangement, the family history may be unknown.

●There may be other reasons for a negative family history, including risk-reducing interventions in some family members (eg, cholesterol lowering agent in an individual at risk for coronary heart disease, prophylactic mastectomy in an individual at high risk for breast cancer); incomplete penetrance of a disorder; or the affected individual may be the first in the family to carry the disease-associated gene variant (ie, a new mutation in the index case). (See "Secondary findings from genetic testing", section on 'Likelihood of detecting a secondary finding'.)

It is also important to update the family history at subsequent visits, as the family history is dynamic and disease that was not previously apparent in a family member may become manifest. Follow-up visits should include questioning about recent deaths, births, or new diagnoses of significant conditions in family members.

Educating the patient regarding expectations — Patients should be informed of where they are being referred and what the process for scheduling an appointment will be if known (Will the clinic call the patient, or is the patient being asked to contact the clinic?).

The patient should know the reason for the referral and what question is to be answered (Is the pattern of disease consistent with a hereditary condition? Should the patient's management be altered? What are the risks for family members?).

Because genetic counseling does not always result in a recommendation for genetic testing, it is helpful for patients to be informed that they are being referred to determine whether genetic testing would be appropriate, rather than to have genetic testing. If the sole expectation of the visit is to have a genetic test done and this does not happen, patients can be frustrated rather than valuing that their risks and management could be better determined by other means, such as a family history-based assessment.

For individuals with a family history of a consanguineous relationship (ie, a common ancestor shared by both partners), there may be an increased risk of adverse pregnancy outcomes such as fetal congenital anomaly, stillbirth, or perinatal mortality. The rate of consanguinity varies significantly between populations. While cultural norms may promote higher rates of consanguinity in some groups, it is prudent to assess the possibility of consanguinity within all families [23].

FAMILY HISTORY — The initial step in assessing inherited risk for many chronic conditions is collecting data related to the family history. The history is then reviewed for patterns that would suggest a specific mode of inheritance. (See 'Use of family history to assess genetic risk' below.)

A 2009 panel sponsored by the National Institutes of Health evaluated evidence regarding the accuracy and effectiveness of obtaining a family history in the primary care setting [24]. The panel found there is limited scientific evidence regarding how best to collect the history, the key elements of the history, the accuracy of reported history, or the impact of a positive family history on patient outcomes. Research published subsequently has confirmed that there are many barriers to family history collection, including the time it takes to collect the history, the process of collection, and, for some clinicians, which questions to ask in the first place [25,26]. However, the family history remains a starting point for determining whether an individual would benefit from a genetic consultation, despite the inability to identify all families with inherited disorders.

Collecting the information — One goal of obtaining a family history is to identify conditions that may be familial and determine if the patient would benefit from referral to a genetic service [13]. There is no evidence for a best way to obtain a family history in terms of instrument (using a form or interview) or format (open or closed questioning) [27]. Researchers have developed a variety of forms and methods of collecting information, and most electronic medical record vendors are developing data collection formats that capture structured data elements and tie them to Systematized Nomenclature of Medicine (SNOWMED) terms. Algorithms could then be available to integrate decision support for medical management, including screening and referral for a genetic evaluation.

History from the patient — When possible, patients referred for genetic counseling should be encouraged to complete written or online family history questionnaires prior to their initial visit. Collecting the family history in advance of the visit allows patients to contact relatives and verify information. Medical information from blood relatives on the maternal and paternal sides of the family should be included, along with the causes and ages of death and/or previous genetic testing information. The patient should be aware that, for the purpose of genetic counseling, the history does not include relatives through adoption or marriage.

Many genetics services send questionnaires to the patient (or family) prior to their initial visit. Alternatively, online resources and tools for collecting family history information and constructing a pedigree from other organizations may be used. (See 'Pedigree' below.)

History obtained by a clinical geneticist or genetic counselor — The family history obtained by a genetics specialist is considerably more detailed than is feasible in the primary care setting (see 'Family/medical history from the referring clinician' above). Depending on the family size, obtaining the family relationships and relevant health information can take between 15 and 30 minutes. This level of detail and accuracy is sometimes necessary for making precise risk estimates, estimating the likelihood of genetic disease, and making management recommendations.

A family history taken by a genetics service typically is targeted to the condition of concern and includes at least three, possibly four, generations: the patient's parents, siblings and children; grandparents, grandchildren, aunts and uncles; nieces and nephews, and first cousins. Information includes current age, health status, age at death and cause of death, and medical diagnoses with related environmental exposures.

When a possible pattern of disease is noted, more focused questions are asked to assess for features of relevant syndromes and to direct the assessment. Review of family members' medical records can confirm diagnoses when there is uncertainty or resolve inaccuracies if family members provide differing information [13,28].

Documentation — The family history should be clearly and completely documented in the medical record, whether collected during the session or as part of a patient-completed intake form.

Key components — Appropriate documentation should include the following information:

●Condition(s) reported.

●Consanguinity and other information about the family that could impact genetic risk.

●Relationship of affected individual to the patient.

●Age of family members at onset of condition.

●Relevant information regarding unaffected individuals in the family, although the format of many electronic health records (EHRs) does not allow this information to be easily recorded as part of the family history. (See 'Electronic health record' below.)

Pedigree — Many genetics professionals use a pedigree or family tree for documentation. An example of a four-generation pedigree is provided in the figure (figure 2) and the components are described below:

●The pedigree/family tree should be centered on the patient.

•When the patient is an adult, it will extend upward to include parents, aunts, uncles, and grandparents; laterally to include siblings and cousins; and downward to include children and grandchildren.

•If the patient is a child, it usually extends upwards to the grandparents.

●Individuals are denoted with boxes (males), circles (females), or diamonds (unknown sex). The National Society of Genetic Counselors 2008 guideline suggests a diamond can be used to represent transgender individuals [29]. However, another study suggests pedigree nomenclature revisions may be warranted [30].

●A deceased individual is denoted by a strikethrough, and members who are affected by a specific condition are shown by shading part or all of the pedigree symbol.

●Current age (or age at death) and medical conditions are listed below each symbol.

●In families where more than one major medical condition is segregating, it is important to assure that shading is consistent for each condition and a legend is created to explain the regions that are shaded for each condition. Rarely, it may be worthwhile to generate more than one pedigree (eg, one for cancer-related conditions and one for heart disease) [29].

Sample pedigrees illustrating commonly used symbols and their meanings are available on various websites such as one from Cancer.gov. Regardless of the symbols used, a legend or similar information is helpful to clarify the meaning of any symbols that could be confusing.

Electronic health record — Many EHR systems lack the ability to include all of information necessary for genetic counseling in the family history section of the record, especially information about ethnicity/ancestry and unaffected family members, and few have the capability to create a pedigree. Research to improve these areas is ongoing [31].

Use of family history to assess genetic risk — Key factors that suggest the presence of a genetic disorder include the following:

●Multiple affected individuals in multiple generations from either side of the individual's family.

●Disease occurrence at an earlier age than usual.

●Close degree of relatedness (ie, first- or second-degree relative) between affected relatives and the individual.

●Presence of associated conditions in the family. Examples include breast and ovarian cancer or colorectal and endometrial cancer.

●Atypical presentations of common conditions. Frequently, this involves greater severity than commonly seen, such as bilateral breast cancer or breast cancer in a male relative.

●Presence of consanguinity. Conditions caused by rare recessive mutations are more common in families in which related individuals such as first cousins have children. Consanguinity is generally more relevant in prenatal and pediatric evaluations than for adult-onset conditions.

As noted below, several algorithms and risk prediction tools are available for estimating risk, and others are under development. (See 'Initial risk assessment' below.)

A family history may display various patterns of inheritance.

Inheritance patterns — The following Mendelian inheritance patterns are seen in monogenic conditions (see "Inheritance patterns of monogenic disorders (Mendelian and non-Mendelian)"):

●Autosomal dominant – Autosomal dominant disorders typically show multiple generations of affected relatives, including both males and females (figure 3). Male-to-male transmission may be observed. Approximately half of the children born to an affected person inherit the genetic predisposition to the condition.

●Autosomal recessive – Autosomal recessive disorders show a pattern in which an individual's siblings are more likely to be affected than the parents (ie, it commonly affects one generation of a sibship), as long as there is no consanguinity (figure 4). Males and females are equally likely to be affected.

●X-linked recessive – X-linked recessive disorders typically affect males related to each other through their mothers, or other female family members (figure 5). Father-to-son transmission is not observed, and females are only rarely affected. Grandfather-to-grandson transmission can occur via an unaffected female carrier.

●X-linked dominant – X-linked dominant disorders affect both males and females, although disease typically is more severe (and may be lethal) in males (figure 6). Father-to-son transmission is not observed, but all daughters of an affected male will be affected. Approximately half of the children born to an affected mother will inherit the genetic predisposition.

In addition to the above classic Mendelian inheritance patterns, some monogenic disorders may display an apparently non-Mendelian inheritance pattern because of variable penetrance and/or variable expressivity. In these cases, fewer individuals in the pedigree will have the condition than expected based on the above inheritance patterns. (See "Inheritance patterns of monogenic disorders (Mendelian and non-Mendelian)", section on 'Causes of non-Mendelian inheritance'.)

Still, other conditions are multigenic or multifactorial (resulting from combinations of genetic and non-genetic factors). When conditions are common in the general population, such as breast cancer (1 in 8 lifetime risk for women), or diabetes (1 in 6 individuals over the age of 60), clinicians will often encounter families with multiple affected relatives that may have different genetic causes for their condition, or have a disease because of an interaction between genetic and environmental factors. Despite the contribution of genetic factors to these conditions, the major etiology of disease in the patient may be due to non-genetic factors. As an example, in an individual who received chest radiation to treat Hodgkin lymphoma and subsequently developed breast cancer, the radiation is likely to be the most important contributor to the breast cancer etiology. In these settings, the pedigree shows weak or no apparent correlation between genotype and the presence of the condition.

Resources for information on specific disorders — The following resources provide information about specific genetic disorders:

●GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK1116/) provides overviews of many genetic conditions.

●Medline Plus:Genetics (https://medlineplus.gov/genetics) provides overviews of many genetic conditions.

●The National Society of Genetic Counselors (www.nsgc.org) website provides information on how to find a counselor as well as consumer information on developing a family history and what to expect from a genetic consultation.

●The Online Mendelian Inheritance in Man (OMIM) database (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM) provides a catalog of human genetic disorders.

●The Genetic Science Learning Center (http://learn.genetics.utah.edu/) includes educational and clinical information about genetics and genetic conditions, links to many helpful web sites about genetics, and educational exercises for teaching genetics from classroom to the clinic.

CONTENT OF GENETIC COUNSELING — Once the family history is collected, it is used with the medical history to assess the possibility of an inherited etiology and identify the chance of disease occurrence or recurrence. There are two additional aspects to the process of genetic counseling: helping the individual (and family) understand the medical, psychological, and familial implications of genetic contributions to disease, and helping them adapt to these implications [1]. This education and counseling is typically delivered in a patient-centered manner to enhance patient autonomy.

Initial risk assessment — An initial risk assessment may be conducted by the genetic counselor or clinical geneticist before the first genetic counseling session if sufficient information is available; this is revised as needed once a more complete family history is obtained. (See 'Use of family history to assess genetic risk' above.)

Several models can be used to determine a patient's risk of developing a condition or the risk of inheriting a particular gene variant, some based on empiric data and others based on computer algorithms.

●Models are relatively well developed for many cancer syndromes (including breast, ovarian, colorectal, and prostate cancer). (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'Identification of individuals at risk for Lynch syndrome' and "Risk factors for prostate cancer", section on 'Using risk factors to estimate prostate cancer risk' and "Screening for breast cancer: Strategies and recommendations", section on 'Clinical use of risk prediction models'.)

●Additional models are being evaluated for cardiovascular disease, asthma, diabetes, and some neurologic diseases. (See "Type 2 diabetes mellitus: Prevalence and risk factors", section on 'Prediction models' and "Cardiovascular disease risk assessment for primary prevention: Risk calculators".)

Once an objective risk figure has been determined, it is important to correlate this with the patient's perceptions of risk. For cancer, many people with a history of a specific type of cancer in the family will overestimate their personal risk of developing the familial cancer (and perhaps underestimate their risks of other cancers that may be more common in the general population).

A genetic counselor can provide explanations of penetrance and expressivity and apply these to the patient's family history and personal risk. (See "Inheritance patterns of monogenic disorders (Mendelian and non-Mendelian)", section on 'Penetrance and expressivity'.)

When the patient's beliefs are not concordant with the calculated risk, the genetic counselor and primary clinician can provide ongoing communication, information, and counseling to help the patient understand the implications of the accurate risk estimate.

The initial risk figure may be modified when additional family history information becomes available, lifestyle changes are made, or interventions such as surgery or medical therapy are performed that decrease risk for particular conditions. (See 'Risk modification' below and "Overview of cancer prevention".)

Information and education — The majority of genetic consultations take place over one to three visits.

●Initial visit – Typically, initial genetic consultations are provided in person, although the use of telehealth (telephone or televideo) is increasing to make genetic services more accessible. The initial visit focuses on reviewing information, providing accurate risk assessment information about personal and family risk, and addressing psychosocial issues. (See 'Initial risk assessment' above and 'Psychosocial support' below.)

When appropriate, the options for genetic testing are discussed, along with the possible outcomes of testing and a plan to communicate the result. This discussion forms the basis of the informed consent process. (See 'Informed consent for genetic testing' below and "Genetic testing".)

For patients who have received information about secondary findings (also called incidental findings) from genomic sequencing, the initial visit may be used to help the patient and referring clinician prioritize the findings and decide which (if any) require further investigation. Novel counseling approaches may need to be developed to convey this information to patients effectively and efficiently. (See "Secondary findings from genetic testing".)

For patients for whom genetic testing is not appropriate or those who elect not to be tested, risk estimates and management recommendations are made based on personal and family history; these are termed empirical risk estimates.

●Subsequent visits – If genetic testing is pursued, there usually will be a follow-up visit or telephone call to discuss results and management implications. Some centers may provide genetic test results by telephone or other service delivery models such as televideo. Additional follow-up visits may be scheduled to assist the patient and their family in better understanding the implications of the result and help to make more challenging decisions regarding strategies for risk reduction.

Informed consent for genetic testing — Informed consent, a tenet of patient-centered medicine, is a foundation for the voluntary nature of genetic testing. Informed consent means the patient fully understands and agrees to the procedure. When offering genetic testing, especially to unaffected individuals, most clinicians follow language from the Department of Health, Education, and Welfare, which encourages the patient to voluntarily exercise free power of choice, without any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion [32]. (See "Informed procedural consent".)

Consent requires discussion that includes the details of the testing and its risks, benefits, and limitations, including the sensitivity and specificity of different genetic tests.

The potential results, including the possibility of an inconclusive or unexpected result, are also included in the discussion. It is also important for the patient to know if management options will change based on the result prior to agreeing to a test, and what these revised management options might be.

Discussion about the Genetic Information Non-Discrimination Act (GINA) and potential insurance concerns is often a part of informed consent discussions, especially if the participant is not affected with disease [33,34]. (See "Genetic testing", section on 'Genetic discrimination'.)

Two exceptions exist to the general practice of obtaining informed consent for genetic testing.

●Newborn screening – Newborn screening in the United States does not involve active consent. Parents or caregivers who do not want their child tested can "opt out" of newborn screening by requesting and signing a form that indicates their refusal.

●Diagnostic evaluation – Genetic testing is sometimes considered part of the diagnostic evaluation, especially for a child with disease that may have a genetic component. In such cases, less of an effort may be made to obtain fully informed consent. However, it is very important that genetic testing options and procedures are explained as much as possible to parents and caregivers.

Consent for multigene testing or whole exome sequencing — Informed consent for multi-gene testing (eg, gene panels) as well as next-generation sequencing (eg, whole exome or whole genome sequencing) differs from consent for testing that is targeted for a known condition. Consent for next-generation sequencing is more challenging because the likelihood of unexpected results and secondary findings increases dramatically when large regions of an individual's genome are sequenced. Patients will need to be informed about the various types of information that may come from this testing, which may include secondary findings and variants for which the clinical significance is uncertain. Additional research is needed to determine how to consent individuals appropriately for large-scale sequencing, as well as how to return information in a meaningful way, and how to store and analyze genetic data. These subjects are discussed in more detail separately. (See "Secondary findings from genetic testing", section on 'Informed consent'.)

Questions that may arise related to a genetic test result — The following questions are important to consider when offering genetic testing and providing results, especially if the likelihood of a positive result is significant.

●Does the person providing results to the patient have an adequate understanding of the results to supply accurate information and answer questions appropriately (or provide the name of a specialist who can do so)?

●Has sufficient time for discussion of potential results and answering questions been allotted?

●Does the patient understand the result and its implications?

●Have potential psychosocial consequences of the test results been addressed?

●Are there other family members who should be notified of the results, and how will that happen?

●Are there reproductive implications of the results?

●Do other specialists need to become involved?

●Should changes be made in disease screening?

●What interventions are appropriate?

●What written or electronic resources have been made available to the patient?

Ethical issues related to the disclosure of genetic information to family members, testing of children, and potential for genetic discrimination are presented in detail separately. (See "Genetic testing", section on 'Ethical, legal, and psychosocial issues'.)

Psychosocial support — Supporting the patient in decision-making and coping are essential components of genetic counseling. Assuring that the patient has sufficient support to make decisions is vital to maintaining patient autonomy, which is a central tenet in genetic counseling. Understanding the potential responses to difficult or unexpected news and being able to respond in a productive manner is essential to long-term acceptance of genetic information and management options. (See "Genetic testing", section on 'Psychosocial consequences of testing'.)

Psychosocial support may take many forms depending on the needs of the patient. This is facilitated by providing accurate and appropriate information in an empathic environment. In addition, other professionals affiliated with the center such as chaplains, nutritionists/dieticians, social workers, nurses, or researchers, may provide additional support. Information about support groups may also be an important consideration for affected individuals, families, and caregivers.

Many centers also obtain information about the psychosocial impact of the condition on the family, with particular regard to experiences in caregiver roles or early deaths.

Risk modification — The genetic counseling session also provides information about risk modification strategies (if available) that may be appropriate for the patient and/or family. This may involve more intensive screening (earlier, more frequent, other modalities), lifestyle or dietary modifications, and/or medical or surgical interventions.

Examples include the following:

●Familial cancer syndromes – Additional screening tests may be used for the patient with a familial cancer syndrome. In some cases, this may involve formal screening tests. In others, it may be useful to screen for (and alert the patient about) possible symptoms related to the other malignancies. As an example, a patient with hereditary breast and ovarian cancer syndrome is at risk for both types of cancers and may have earlier mammography and/or clinical breast examinations and/or prophylactic surgeries. For patients with familial polyposis, colonoscopy screening is initiated at an earlier age than the general population.

If genetic testing identifies a pathogenic or likely pathogenic variant, other at-risk family members can also be tested for the specific variant. For many conditions, screening and risk reduction strategies can be implemented for appropriate family members. Counseling regarding the risk in family members and discussions about family member testing and their notification (typically, by the affected individual using a letter prepared jointly by a genetic counselor and physician) are discussed separately. (See "Genetic testing".)

●Prenatal counseling – Testing for the partner may be indicated for autosomal recessive conditions when a couple is referred for prenatal counseling. (See "The preconception office visit", section on 'Heritable diseases'.)

The counselor and the referring clinician may also work together to coordinate long-term risk modification and management for patients and affected family members. The primary care or specialty care clinician is often responsible for long-term follow-up. The family history can help to personalize health lifestyle messages [35,36].

For some genetic conditions, there are no available risk modification measures or medical management changes made based on a positive test result or genetic diagnosis. In these cases, genetics and specialty professionals can provide guidance on:

●Supportive treatment and adaptation (physical or occupational therapy).

●The importance of planning.

●Implications for at-risk first-degree relatives, although many family members will not pursue testing when the associated disease is incurable.

RESOURCES FOR GENETIC COUNSELING

Where to refer — Genetic evaluation services can be provided by individuals with different educational backgrounds and areas of expertise [37]. In the United States, this may include clinical geneticists, genetic counselors, or specialists with expertise in a specific disease background.

●Genetic counselor – A genetic counselor has a graduate degree (typically a Master's degree) in genetic counseling, with education in medical genetics, psychological support, and counseling. Certification is done through the American Board of Genetic Counseling (ABGC) [38].

●Clinical geneticist – A clinical geneticist is a physician with specialized training in genetics. Board certification in subspecialties of clinical genetics is done through the American Board of Medical Genetics and Genomics (ABMGG) [39].

●Other specialists – A specialist in any medical specialty can obtain additional training or experience in genetic counseling as it relates to their area of specialization. As an example, in a center that cares for many patients with sickle cell disease, one of the clinicians may develop expertise in the genetics and counseling of affected individuals and carriers.

●Nurses – Nurses in various specialties can obtain clinical genomics nurse credentials through the Nurse Portfolio Credentialing Commission (nurseportfolio.org) [40].

Online tools for locating a counselor — Resources for locating a genetic counselor are available online:

●The National Society of Genetic Counselors (NSGC) in the United States has a locator tool for counselors according to geographical location and area of specialization (https://www.nsgc.org/page/find-a-genetic-counselor).

●The American College of Medical Genetics and Genomics (ACMG) has a searchable database for clinics that provide genetic counseling (https://clinics.acmg.net/).

●The Canadian Association of Genetic Counselors (CAGC) has a locator tool that filters searches by province and type of services (https://www.cagc-accg.ca/).

●The National Cancer Institute (NCI) in the United States has a searchable directory for counselors with expertise in cancer syndromes (http://www.cancer.gov/about-cancer/causes-prevention/genetics/directory).

●The March of Dimes in the United States will provide information about services through contact with its local chapters (http://www.marchofdimes.org/contact-us.aspx).

●A centralized genetic counseling service for United States Veterans known as the Genomic Medicine Service (GMS) was established in 2008 and is available through many of the Veteran's Administration medical centers [41]. This service provides genetic evaluation primarily by video (telehealth) for individuals for whom in-person counseling is not feasible.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Genetic testing (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Genetic counseling is the process of helping people understand and adapt to the medical, psychological, and familial implications of genetic contributions to disease. Most consultations occur over one to three visits. A preliminary assessment based on available data and family history (figure 1) may be conducted before the patient is seen. The initial visit focuses on reviewing information, providing accurate risk assessment, and addressing psychosocial issues. (See 'Definition of genetic counseling' above.)

●Indications – Individuals with strong family histories for conditions with known genetic bases considered high risk (table 2) should be offered referral to a genetics professional. Referral may also be appropriate if there is uncertainty about the genetic contributions to a disease in a family, patient anxiety about a family member's condition, or misunderstanding of risk. (See 'Indications for referral' above.)

●Preparation – The referral should include specific questions to be addressed, a summary of the family history, and patient's medical history, and results of available testing. The patient should understand that they are being referred to determine whether testing would be helpful. (See 'Preparation for referral' above.)

●Risk assessment – The family history is the initial step in assessing inherited risk for many chronic conditions. When possible, patients should be encouraged to complete written or online family history questionnaires prior to their initial visit. Online resources are available for collecting family history information and constructing a family tree (pedigree) (see 'Pedigree' above). The family history should be clearly and completely documented in the medical record. (See 'Family history' above and 'Initial risk assessment' above.)

●Support and advice – The genetic counseling session also provides psychosocial support and information about risk modification strategies that may be appropriate for the patient and/or family. This may involve more aggressive screening (earlier, more frequent, other modalities), lifestyle or dietary modifications, and/or medical or surgical interventions. The counselor and referring clinician can coordinate long-term risk modification and management for patients and affected family members. The primary care clinician is often responsible for long-term follow-up. (See 'Questions that may arise related to a genetic test result' above and 'Psychosocial support' above and 'Risk modification' above.)

●Testing and disclosure – Separate topic reviews discuss genetics terminology, genetic testing, personalized medicine (including direct-to-consumer testing), genomic sequencing, and disclosure of incidental findings from genetic testing. (See "Genetics: Glossary of terms" and "Genetic testing" and "Personalized medicine" and "Secondary findings from genetic testing".)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Vickie Venne, MS, CGC, and Deborah Hartzfeld, MS, CGC, who contributed to earlier versions of this topic review.