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".)

BACKGROUND

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.

●Interpretation and explanation of genetic test results.

●Education of the patient (and family/caregivers) 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/caregivers, referring clinician, medical record, and test results from other sources.

Reasons for accessing genetic counseling — Historically, genetic counseling and testing has been guided by family history. However, genetic testing is increasingly performed for indications based on the patient's personal history alone or very broad family history criteria.

Genetic counseling can be conducted at any time along a life spectrum, from pre-conception to old age. The growing indications for genetic testing have necessitated the development of novel strategies for risk assessment and facilitating informed decision making. Automated pre-test counseling approaches such as videos, web-based tools and chatbots are being studied in a variety of settings and for different indications [2-7]. These have been shown to be effective for providing pre-test education and allowing for genetic testing to be scaled up to larger populations.

Germline genetic testing is also increasingly important for diagnosing and planning treatment of diseases. Approved treatment of BRCA-related cancers with poly-ADP ribose polymerase (PARP) inhibitors has resulted in recommendations for genetic testing of all patients diagnosed with epithelial ovarian cancer, adenocarcinoma of the pancreas, and advanced prostate cancer regardless of age or family history [8]. Oncologists and surgeons are ordering genetic testing, often without pre-test counseling with a genetic counselor [9-15].

Point-of-care genetic testing — Integration of genetic testing into non-genetics clinics is referred to as point-of-care (POC) genetic testing. This has also been shown to be an effective approach for increasing access to genetic testing by minimizing barriers related to having separate appointments for genetic counseling and ensuring that test results are back in time to use for treatment planning.

Traditional genetic counseling paradigms have been incorporated when rapid whole genome or whole exome sequencing is used in the diagnostic evaluation of newborns and children admitted to the hospital with severe health issues.

Exome or genome sequencing can improve the diagnostic yield and shorten the time to diagnosis, but this testing approach can also result in secondary findings [16,17]. (See "Secondary findings from genetic testing".)

Pre-test genetic counseling is recommended for patients undergoing testing, but the pre-test counseling process cannot include all possible findings and their implications. (See 'Consent for multigene testing or whole exome sequencing' below.)

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 treat or 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.

Referral for genetic counseling should not be dependent on the patient’s knowledge of, access to, or ability to share their family history. Patients may not be able or willing to share family history for multiple reasons. Though being able to provide an extensive family history or to obtain records and medical details from relatives can help guide counseling and inform patient decision making, patients lacking such information will nonetheless benefit from counseling and should be referred if appropriate.

Patients may be referred for genetic counseling for risk assessment to discuss whether genetic testing would be appropriate for them. This process 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.

As noted, patients may be referred to genetic counseling after genetic testing has been performed. The National Comprehensive Cancer Network suggests several post-test scenarios that warrant a referral. While these were developed for cancer patients, they are widely applicable.

Post-test indications for referral include one or more of the following [18]:

●Identification of a variant that is pathogenic, likely pathogenic, or of uncertain significance (VUS) and requires additional evaluation

●Negative results in an individual who may be at risk of a genetic condition based on positive personal history

●Individual concerned about risk due to positive family history when a familial variant has not been identified in the kindred

●Possible mosaicism

●Questions about whether the variant is germline or somatically acquired

●Questions about how to interpret direct-to-consumer test results or polygenic risk score results

The primary care team should be comfortable initiating the process by obtaining an initial family history, categorizing the likely genetic risk, and assisting the patient in finding an appropriate genetics professional. (See 'Family/medical history from the referring clinician' below and 'Increased risk' below and 'Resources for genetic counseling' below and 'Where to refer' below.)

Increased risk — For multifactorial conditions, empiric risk estimates can sometimes be made on the basis of the patient's personal and family history. 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) [19].

●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 [20,21]. 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 everyone with a first- or second-degree relative with ovarian cancer [18]. 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 [19]. Similar prevalence of high-risk patients has been reported in other studies [22]. 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 [23].

Uncertainty about genetic basis — For many common adult-onset conditions such as diabetes, autoimmune disorders, and psychiatric conditions, clinicians may be uncertain whether there is sufficient information about the genetic etiology for a referral to be useful.

The rapid rate of gene discovery following the mapping of the genome and the advent of genome-wide association studies (GWAS) 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. However, not all conditions may fit within the scope of an institution's genetics specialty clinics.

●The National Society of Genetic Counselors (NSGC) has a "Find A Genetic Counselor Tool" that can be used to search for genetic counselors with certain specializations. (See 'Online tools for locating a counselor' below.)

●Professional societies can be checked to see if they have statements or guidelines about whether genetic testing is indicated for a particular condition. Professional society information for selected monogenic conditions is listed in UpToDate genetic testing monographs.

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 [24].

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

PREPARATION FOR REFERRAL — Recommendation from the patient's clinical team is one of the strongest predictors of patients following through with a genetics referral.

It is therefore essential that the referring clinician prepare the patient and make the counseling appointment as useful as possible.

A brief discussion with the patient should cover the following points:

●Features of the family history that prompted the referral.

●Explanation why the session is important or will be helpful.

●Review of the likely content of the counseling visit [25].

●Instruction to obtain (if possible) additional relevant family history from informed family members.

●The name and professional affiliation of the person who will be contacting the patient.

•Historically, genetic counseling has been associated with universities and major medical centers.

•Community hospitals are often including the service.

•Companies that offer counseling using telehealth services (eg, telephone, videoconferencing) are becoming more common.

Some 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. Insurance plans vary, and it is important to have the patient check with their 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 [26]. 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:

●A focused question or request – 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."

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

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

●Prior genetic testing – This includes prior genetic testing performed on the patient and/or relatives, accompanied by the results, if known.

Family/medical history from the referring clinician — The American Medical Association (AMA) recommends collecting family history for the following reasons [27]:

●To determine risk for disease

●To determine if treatments or screening would be appropriate to reduce risk

●To be alert to early symptoms

●To help encourage lifestyle changes to minimize risks and maintain health

Ideally, family history includes first-, second-, and third-degree relatives, as listed in the table (table 1) and illustrated in the (figure 1). Key questions to ask in obtaining a family history relate to patient concerns about disease, problems with pregnancy, congenital anomalies, early deaths or disease onset, and nongenetic risk factors for disease such as use of tobacco or alcohol use and disease-specific occupational exposures. Patients may be unaware of precise medical diagnoses in relatives but can provide revealing information regarding symptoms, surgeries, and medication use.

Additional questions related to the size of the kindred (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. This can be asked in several ways, such as "Were your parents related by blood prior to marriage?" or "Did your parents share a common relative prior to marriage?"

Patients may neglect to mention the medical conditions of siblings or other relatives who have died (often the most informative information). For certain conditions (ie, monogenic causes of pulmonary disease), this can include children born shortly after birth. Direct questions addressing these issues are therefore helpful.

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 relative may become manifest. Follow-up visits should include questioning about recent deaths, births, or new diagnoses of significant conditions in relatives. If a patient does not know their family history, that should also be documented.

FAMILY HISTORY COLLECTION DURING A GENETIC COUNSELING APPOINTMENT — 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.)

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/caregivers) 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.)

To improve accuracy, some software programs allow patients to invite family members to input their medical history directly into the online tool in a HIPPA-compliant framework.

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 [26,28].

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 — Electronic family history collection tools likely will be an important resource for identifying patients who meet criteria for genetic testing. However, improving collection of family history during routine medical visits will likely still be needed to identify most patients.

Clinical decision support tools integrated into the electronic health record (EHR) are intended to reduce disparities [31]. However, reliance on family history collection using the EHR through routine care may actually exacerbate disparities in access to genetic services. (See 'Algorithms for risk prediction' below.)

Many tools for facilitating family history collection are also being developed and studied [32]. While these have often been shown to be effective for group studies, they have generally not been integrated into the EHR, they are specific for collecting family history for one or only a few indications, and they have not been used at scale in diverse populations.

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.

Lack of family history does not rule out a genetic condition. Recessive or X-linked inheritance, de novo pathogenic variants, variable penetrance, small family size, and lack of family history information may all prevent a hereditary condition from being evident. However, some testing criteria are still based on family history. (See 'Reasons for accessing genetic counseling' above.)

Algorithms for risk prediction — Several algorithms and risk prediction tools are available for estimating risk for specific conditions, and others are under development. (See 'Initial risk assessment' below.)

Algorithms using structured family history and natural language processing are being studied as tools for screening populations within a health care system, particularly primary care patients, to identify criteria for genetic testing [33,34]. A study of family history collection across two health care systems also found that family history was collected less often and less thoroughly in patients who were non-White, Hispanic, non-English speaking, and male [35-37].

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 one-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 one-half of the children born to an affected mother will inherit the genetic predisposition.

In addition to these classic Mendelian inheritance patterns, some monogenic disorders may display an apparently non-Mendelian inheritance pattern because of variable penetrance, variable expressivity, mosaicism, parent-of-origin effects, or de novo mutations. 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'.)

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 — UpToDate includes topics on the genetics of many common and rare diseases, providing information on specific genetic disorders, their manifestations, associated features, and inheritance patterns.

For additional information, the following resources are recommended:

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

Models have been developed to determine a patient's risk of developing a condition or the risk of inheriting a particular gene variant. Some are based on empiric data and others based on computer algorithms.

●Numerous relatively well-developed risk assessment models are available 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'.)

●Models with variable predictive accuracy are also available for non-malignant disorders, including cardiovascular disease, asthma, diabetes, and some neurologic diseases. Efforts to improve these algorithms are ongoing. (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 – Genetic consultations can be provided in person, by telephone, or by video.

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".)

Many patients will be referred to genetic counseling after genetic testing. In this situation, the visit will focus on explaining the results and implications for the patient and relatives. (See 'Reasons for accessing genetic counseling' above and "Secondary findings from genetic testing".)

In some cases (genetic testing inappropriate, individual elects not to be tested, uninformative result), 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. Some centers have clinics that provide ongoing management for people diagnosed with certain genetic conditions, such as metabolic disorders, cancer predisposition, or hereditary heart diseases.

Informed consent for genetic testing — The discussion and informed consent process includes potential results and the possibility of an inconclusive or unexpected result. 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 [38,39]. (See "Genetic testing", section on 'Genetic discrimination'.)

It is appropriate to tailor the pre-test genetic counseling based on the indication and type of genetic testing. The Clinical Genome Resource's Consent and Disclosure Recommendations Working Group has developed a framework to guide the extent of pre-test and post-test discussions.

Considerations in the type of pre-test counseling needed include [40]:

●Severity of the condition

●Whether genetic testing for that indication has been associated with adverse psychological effects

●Whether the condition is associated with sudden death or complex management

●Availability of educational materials

The average length of consultation varies by the complexity of the medical condition and type of genetic test performed. To guide resource allocation, three types of discussions have been recommended, including:

●Brief communication (requiring <5 minutes) – Sufficient for confirmatory testing in a person who is already affected and family variant testing for conditions with management recommendations.

●Targeted discussion (requiring 10 to 20 minutes) – Appropriate for most medical conditions associated with moderate to high penetrance and management options or for complex tests such as exome or genome sequencing.

●Traditional genetic counseling (requiring >30 minutes) – Recommended for situations such as testing an unaffected person at risk for a familial non-actionable, neurodegenerative condition.

This framework helps to target genetic counseling resources to the patients with the greatest need and also provides guidance for genetic testing indications that could most appropriately be addressed by point-of-care testing or automated approaches.

Newborn screening is an exception that it does not require active consent in the United States. 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.

Consent for multigene testing or whole exome sequencing — Complex tests such as gene panels and whole exome or whole genome sequencing require targeted discussion (10 to 20 minutes) to ensure understanding of the type of possible results to be returned. This includes positive, negative, inconclusive, and incidental/unexpected results and their implications to the patient (medical, insurance-related) and relatives.

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 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 [41,42].

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 [43]. 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) [44].

●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) [45].

●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) [46].

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 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 [47]. 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 topic (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/medical history from the referring clinician' above and 'Family history collection during a genetic counseling appointment' 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.