Genetic Counseling

C H A P T E R

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Genetic Counseling Wendy R. Uhlmann University of Michigan Medical School, Ann Arbor, MI, USA

GENETIC COUNSELING DEFINED AND PROVIDERS Many neurological and psychiatric conditions either are genetic or have genetic factors that contribute to the condition. As a result, a diagnosis can have implications not only for the affected individual but also for family members whose risk may consequently be increased. Providing genetic counseling for patients and their families can be instrumental for care, identifying at-risk relatives and decisions about testing and management. Genetic counseling is defined as: “the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease. This process integrates: • Interpretation of family and medical histories to assess the chance of disease occurrence or recurrence • Education about inheritance, testing, management, prevention, resources and research • Counseling to promote informed choices and adaptation to the risk or condition.”1,2

Traditionally, the genetic counseling approach has been nondirective with presentation of information in an evenhanded way and with an emphasis on patient ownership and autonomy in decision-making. The goal of genetic counseling is to provide patients with comprehensive and understandable information so that they can make informed health care and life decisions consistent with their values, beliefs, and needs.3 Providers with specific expertise and clinical training in genetics include clinical geneticists, genetic counselors, and clinical nurse specialists in genetics. Clinical geneticists complete a residency in clinical genetics (usually after a residency in pediatrics, obstetrics and gynecology, internal medicine, neurology, or other specialty) and are boarded by the American Board of Medical Genetics (or by boards in other countries). Genetic counselors are master’s ­degree-level trained health care providers who are boarded by the American Board of Genetic Counseling (or by boards in other countries) and are licensed providers in many states. Nurses with special education and training in genetics are bachelor’s-level trained genetics clinical nurses (GCN) and master’s-level trained advanced practice nurses in genetics (APNG) and are credentialed by the Genetic Nursing Credentialing Commission (GNCC). Genetic counselors and clinical nurse specialists in genetics provide genetic counseling for patients with neurological ­conditions in general pediatric and adult genetics clinics, and also work in neurology clinics and some in psychiatric clinic settings. Resources for locating genetics clinics and certified genetics providers in the United States are in Table 12.1. For patients residing far away from genetic service providers, there are companies that offer phone genetic counseling that can be ascertained through an Internet search.

WHICH PATIENTS COULD BENEFIT FROM GENETIC COUNSELING? Patients diagnosed with a hereditary condition will be faced with adjusting to the condition and informing at-risk relatives and can benefit from genetic counseling. They may need to make decisions about genetic testing and other family members may consider testing to determine their status. If a patient is of reproductive age, there may be reproductive

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TABLE 12.1  R  esources for Locating Genetics Clinics and Certified Genetics Providers in the United States Organization

Website

American Board of Genetic Counseling

www.abgc.net

American Board of Medical Genetics

www.abmg.org

American College of Medical Genetics and Genomics

www.acmg.net

GeneTests—Clinic Directory (includes international)

www.genetests.org/clinics/

International Society of Nurses in Genetics

www.isong.org

National Society of Genetic Counselors

www.nsgc.org

Orphanet (international)

www.orpha.net

and prenatal testing decisions to make. Particularly when there is no family history of a genetic condition, the patient has no context for the diagnosis and likely will require more education about a condition, familial implications and support. The affected patient’s relatives, especially siblings and children, can benefit from genetic counseling to learn about their risks and genetic testing options to determine their risk. For asymptomatic individuals at 50% risk for a neurogenetic condition like Huntington disease, there are predictive genetic testing guidelines that specifically require genetic counseling.4,5 The guidelines describe the testing process, essential information to convey, communication and implications of results, and emphasize that the decision should be voluntary, informed, and made by the patient— not by the physician or anyone else. The guidelines for predictive genetic testing for Huntington disease have been adapted for predictive genetic testing for other hereditary neurological conditions including early-onset Alzheimer disease,6,7 amyotrophic lateral sclerosis,8,9 and frontotemporal dementia/autosomal dominant dementias.7,10

COMPONENTS OF GENETIC COUNSELING AND CASE PREPARATION A typical genetic counseling session can last 1 to 1.5 hours. The components of genetic counseling are listed in Table 12.2 and discussed below. There is extensive case preparation that typically needs to be done before a patient is seen,11 and resources to accomplish this work can be found in Uhlmann and Guttmacher (2008)12 and Uhlmann (2009).11 Conducting a literature search is important for ensuring that information is up-to-date given the rapid pace of advances in genetics. In addition to literature searches, key resources for obtaining information about genetic conditions include MedGen (www.ncbi.nlm.nih.gov/medgen), GeneReviews (www.ncbi.nlm.nih.gov/books/ NBK1116/) and Online Mendelian Inheritance in Man (OMIM; www.ncbi.nlm.nih.gov/omim). OMIM can also be used to generate differential diagnoses using the search function and providing clinical features. Obtaining a three-generation pedigree from the patient up through grandparents is standard in genetic counseling and is used not only for the basis of risk assessment but also can provide insights about the patient’s family dynamics, support and psychosocial issues. Pedigree symbols utilized are summarized in articles by Bennett et al.13,14 Like any medical interaction, genetic counseling consists of both obtaining and providing information. What differs is the nature of the interaction, approach and time involved. The National Society of Genetic Counselors has information about genetic counseling for patients and providers and videos of simulated counseling sessions available at TABLE 12.2  Components of Genetic Counseling Contracting (ascertaining patient’s questions/concerns; providing overview of clinic visit) Information gathering (family and medical histories) Physical examination (if indicated) Risk assessment (determination of likely pattern(s) of inheritance, risks) Education about genetic condition (clinical features, prognosis, management, inheritance and implications for patient and family members) Ascertaining and addressing psychosocial issues/concerns Discussion of genetic tests/other tests/evaluations/referrals to consider Provision of resources about the genetic condition and contact information for national organizations/support groups Facilitating decision-making I.  GENERAL CONCEPTS AND TOOLS



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Risk assessment

their website. The American College of Medical Genetics and Genomics, the Genetics in Primary Care Institute (www. geneticsinprimarycare.org) and the National Coalition for Health Professional Education in Genetics/The Jackson Laboratory (www.nchpeg.org) have developed clinical resources and point of care tools for physicians and providers that explain basic genetics concepts and genetic testing.

RISK ASSESSMENT Establishing the pattern of inheritance of a genetic condition in a family can be critical for making a diagnosis, identifying at-risk relatives and providing an accurate risk assessment. The three-generation pedigree is used to evaluate the family history information to determine likely pattern(s) of inheritance; when indicated and possible, medical records are requested to confirm reported diagnoses. Assessing transmission, generations and genders affected is important for determining inheritance. For X-linked recessive, X-linked dominant and mitochondrial conditions, there can be no male-to-male transmission. Autosomal recessive inheritance is the most likely explanation when individuals are affected in a single generation and/or there is consanguinity or the patient is of an ethnicity with high frequency of carriers of a condition (for example, Tay–Sachs disease in the Ashkenazi Jewish population). Depending on the pattern of inheritance, gender, and relative(s) affected, recurrence risks can range from general population risks to 100% (Table 12.3). Sometimes a condition can have multiple patterns of inheritance (Table 12.3). Other factors that can impact pedigree interpretation and risk assessment include whether the genetic condition has heterogeneity, reduced penetrance, variable expressivity, anticipation, gonadal or somatic mosaicism. Nonpaternity could impact pedigree interpretation. Bayesian analysis can sometimes be used to modify a patient’s risk by ­factoring TABLE 12.3  Risks and Examples of Genetic Conditions Associated with Different Patterns of Inheritance Pattern of inheritance

Risks (for the affected individual)

Examples of conditions

Autosomal dominant

Note: Penetrance impacts risk to be affected. Children: 50% risk to be affected Siblings: 50% risk to be affected if a parent has gene mutation Parents: A parent may have gene mutation or could arise de novo in affected individual

Charcot–Marie–Tooth syndrome Hereditary spastic paraplegia Huntington disease Myotonic dystrophy

Autosomal recessive

Children: All will be obligate carriers. Risk to be affected generally < 1% (depends on carrier risk in the general ­population) but if partner is a carrier, then risk is 50% Siblings: 25% risk to be affected. If unaffected, 2⁄3 (67%) risk to be a carrier Parents: Both parents would be obligate carriers

Friedreich ataxia Hereditary spastic paraplegia Spinal muscular atrophy Wilson disease

X-linked recessive

Carrier female: (Note: some carrier females can be “manifesting carriers” and have mild symptoms due to skewed X-inactivation) Sons: 50% risk to be affected Daughters: 50% risk to be carriers Affected male: Sons: All unaffected Daughters: All carriers Affected female (can result from affected father and carrier mother): Sons: All affected Daughters: All carriers

Becker/Duchenne muscular dystrophy Charcot–Marie–Tooth syndrome Fragile X syndrome Hereditary spastic paraplegia

X-linked dominant

Few conditions with this pattern of inheritance. Most X-linked dominant conditions are lethal in males. Females are more mildly affected Female with X-linked dominant condition: Daughters: 50% risk Sons: 50% risk

Aicardi syndrome Incontinentia pigmenti Rett syndrome

Mitochondrial

Affected status will depend on percentage of mitochondria with mutation that are inherited, 0–100% Affected female: Will transmit mitochondria to all of her children. Children may or may not be affected Affected male: Will not transmit mitochondria to any of his children

Leber hereditary optic neuropathy (LHON) Mitochondrial encephalopathy, lactic acidosis, strokes (MELAS) Mitochondrial encephalopathy with ragged-red fibers (MERRF)

Complex/multifactorial

Empiric risk studies. Increased risks based on relatedness (1st degree relative > 2nd > 3rd)

Alzheimer disease Bipolar disorder Schizophrenia

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in family history, gender, age, clinical status, or test results and is often used to derive the risk modification figures in genetic test reports. For non-Mendelian conditions, empiric risk studies are utilized. One resource that has a summary of empiric risk studies for psychiatric conditions is the National Coalition for Health Professional Education in Genetics/The Jackson Laboratory. Fundamental to genetic counseling is explaining to a patient how a condition is inherited and the implications for other relatives. Online resources for patient information about patterns of inheritance include: Genetics Home Reference (http://ghr.nlm.nih.gov/), Centre for Genetics Education (www.genetics.edu.au/) and for this information in different languages EuroGentest (www.eurogentest.org/), Genetic Alliance UK (www.geneticalliance.org. uk/) and Centre for Genetics Education.

COUNSELING AND EDUCATION ABOUT THE GENETIC CONDITION Central to genetic counseling is helping patients understand the genetic condition and educating them about the clinical features, inheritance, and familial implications, prognosis, treatment, management, and testing options. Creation and use of counseling aids (e.g., developing and printing PowerPoint slides, purchase of genetic counseling aids) and use of photos and diagrams from patient brochures and internet searches can be instrumental in clearly presenting complex information and facilitating patient understanding about the genetic condition. Exploring a patient’s journey with a diagnosis and/or family history of a genetic condition can help in identifying stressors, challenging issues and difficult family dynamics and assist in normalizing reactions and identifying supportive resources. Educating patients about their genetic condition in understandable terms and providing resources is important both in terms of their adaptation and because frequently they may in turn have to be the ones to communicate this information to other at-risk family members.15

GENETIC TESTING Genetic testing generally is not as simple as just checking off a box on a form. For many conditions, genetic testing is not yet standard of care and there is only a single or few labs that offer testing, particularly if the condition is rare. Uses of genetic testing include diagnostic, predictive, carrier and prenatal applications, which raise different issues and have different implications even though the same analysis from the laboratory standpoint is being performed. Genetics expertise is frequently needed to decide whether genetic testing is indicated, which genetic test to order (e.g., single gene, panel, chromosome microarray analysis, sequencing), select a laboratory, and interpret test results. Depending on the genetic condition, there may be practice guidelines available for genetic testing from the American College of Medical Genetics and Genomics, the National Society of Genetic Counselors, and other professional organizations that can be ascertained by searches of the literature and organization websites and at www.guidelines. gov. For example, the American College of Medical Genetics and Genomics has practice guidelines for Alzheimer disease,6 autism spectrum disorders,16 fragile X syndrome,17 and several other neurological conditions. Laboratories can differ in the tests offered, methodologies used, cost, and result time, even when testing for the same genetic condition. In the United States, the Genetic Testing Registry (www.ncbi.nlm.nih.gov/gtr/) and GeneTests (www.genetests.org) are key online databases that can be used to determine if genetic testing is available; Orphanet can be used to identify international labs offering testing. Selecting the “right test” and the “right laboratory” are important and, given different testing methodologies and sensitivities, can potentially make a significant difference in making a diagnosis. If genetic testing is costly and/or sensitivity is limited, deferring genetic testing may be preferable. DNA banking is an option to consider if a patient’s lifespan is limited and genetic testing is not a reasonable option; generally banking a sample can be done for approximately $100. Genetic counseling can help patients understand the benefits, risks and limitations of genetic testing and make an informed decision. Pre- and post-test counseling and informed consent are essential components of genetic testing. Topics typically covered during pretest counseling and informed consent are in Table 12.4. Online resources for ­patients that explain genetic testing and uses include: Genetics Home Reference, National Human Genome Research Institute, Centre for Genetics Education, Genetic Alliance and EuroGentest. For asymptomatic individuals with a family history of a genetic condition, generally an affected individual needs to be tested first to determine if there is an identifiable mutation(s). In the absence of testing an affected family member, it will not necessarily be known whether an asymptomatic individual who tests negative is in fact a “true negative” for the genetic condition or still at risk (an affected individual may have also tested negative given limitations in testing technology). While genetic testing may not necessarily affect patient care, it can be important for confirming a suspected diagnosis, enable at-risk relatives to have the option of testing and be of use reproductively. I.  GENERAL CONCEPTS AND TOOLS



Test interpretation

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TABLE 12.4  Topics Covered During Pretest Counseling and Informed Consent Genetic test recommended Explanation of test and likelihood of finding gene mutation(s) Benefits, risks and limitations of genetic testing, including psychosocial implications Significance of a result that is positive, negative or a variant of unknown significance and implications for patient and family members Laboratory where sample will be sent Cost and insurance coverage/issues Timeframe for results and how results will be communicated Possibility additional testing of patient and/or family members may be indicated

INSURANCE CONSIDERATIONS AND IMPLICATIONS Insurance coverage of genetic testing and implications results could have for the patient to obtain desired types of insurance are major considerations. Genetic tests can range in cost from a couple of hundred dollars to several thousand dollars. Coverage of genetic testing differs by type of insurance and plan; coverage of genetic testing for patients with Medicaid insurance is particularly difficult to obtain. Insurance generally will not cover the cost of genetic testing if it will not alter a patient’s care. Some insurers will provide pre-authorization for genetic testing. There are some laboratories that offer the service of checking whether the genetic test will be covered by the patient’s insurance. For many patients, a letter of medical necessity will need to be written after a clinic visit to an insurer that includes clinical indication, test requested, CPT (Current Procedural Terminology) codes, lab and costs in order to determine if genetic testing will be covered.11 Patients may be concerned about the potential for stigmatization and discrimination based on their genetic condition or genetic test results. In the United States, the Genetic Information Nondiscrimination Act (GINA), passed in 2008, prohibits discrimination in health insurance and employment based on genetic information. However, this law does not cover life, long-term disability and long-term care insurance. For predictive genetic testing for conditions like Huntington disease, it is particularly important for patients to have desired insurance coverage prior to proceeding with genetic testing. Information about GINA’s health insurance and employment protections can be obtained at www.ginahelp.org. The National Human Genome Research Institute maintains a genome statute and legislative database with information about state laws at: www.genome.gov/PolicyEthics/LegDatabase/pubsearch. cfm. HumGen (www.­humgen.org) is an international database of laws and policies.

TEST INTERPRETATION Genetics expertise is often needed in interpreting genetic test results and determining whether additional genetic testing with different methodologies is indicated. Identification of a gene mutation does not necessarily mean that it is causative of the genetic condition and if present in an asymptomatic individual does not necessarily mean he/ she will become symptomatic. For example, if there is reduced penetrance, it is possible that an individual with a gene mutation may not become symptomatic. Depending on the gene mutation, it could be an unrelated coincidental finding of no significance or could be disease-causing, a common polymorphism, a rare sequence variant, or a variant of unknown significance (VUS). Use of online databases (e.g., ClinVar, locus specific mutation databases) and conducting a literature review can be important for result interpretation. For some conditions, there are genotype– phenotype correlations. Guidance in determining the significance of a gene mutation and how variants of unknown significance are classified, interpreted and reported can be found in the American College of Medical Genetics and Genomics practice guidelines.18–20 Sometimes multiple testing methodologies need to be considered, for example deletion/duplication analysis after negative sequencing results are obtained. Unless the mutation is a known or presumed pathogenic mutation, clarification of test results may require testing additional family members to determine whether the gene mutation(s) are inherited or de novo and whether the mutation(s) track with affected family members. The most reassurance that can be given is to an asymptomatic patient who tests negative for a familial gene mutation—a “true negative” result. Understanding these nuances of testing, determining next steps and explaining the complexities of test result interpretation is central to g ­ enetic counseling. I.  GENERAL CONCEPTS AND TOOLS

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ETHICAL ISSUES Ethical issues can arise in genetic counseling and particularly with genetic testing. In some families, information about genetic conditions is not openly shared or communicated. There can be pressure and coercion by family members to be tested or not tested. While respect for a patient’s autonomy is paramount, ethical issues can arise when one relative’s right to know conflicts with another relative’s right not to know. Given shared genetics, it is possible that an individual’s test results could reveal the genetic status of another family member who did not want their status determined—for example, an adult child who has positive predictive genetic test results for Huntington disease and consequently, their at-risk parent, who did not want their status determined, will now be known positive. Genetics professionals are knowledgeable about ethical issues that can arise and issues to consider. To address and resolve ethical issues, guidelines and position statements from different genetics professional organizations, specific genetic condition guidelines, and hospital ethics committees can be consulted. In general, testing children for adult-onset conditions should be deferred so that the child has an “open future” and can decide for himself/herself whether their status should be determined.21 Generally, testing a pregnancy should only be considered if it will alter the management of the pregnancy. While patients should be encouraged to share genetic information with other at-risk relatives, which should be documented in clinic visit notes, direct familial disclosure of genetic information by physicians is restricted only to those cases where the potential for harm from nondisclosure is significant and specific criteria have been met.22 At the present time, genetics professionals do not have a duty to re-contact patients and patients should be encouraged to re-contact a genetics clinic to learn about genetic advances.23 Additional ethical issues that can arise with genetic testing for neurogenetic conditions are summarized in Uhlmann (2006),24 Roberts and Uhlmann (2013),25 and in this book.

IDENTIFYING SUPPORTIVE RESOURCES FOR PATIENTS Patients leave their doctors’ offices and have to face the challenges of living with or being at-risk for a genetic condition. One of the goals of genetic counseling is to help patients adjust to the genetic condition. As a result of having or being at-risk for a genetic condition, a patient can experience sadness, anger, concern, anxiety, guilt, stress, and other emotions. There can be changes in view of self/self-worth, and family dynamics. Linking patients up with supportive resources and helping them connect with other individuals who are facing similar challenges can be of great benefit. Through their experiences of living with a genetic condition, patients may be aware of helpful resources unknown to health care providers that can benefit other affected individuals. Support group/advocacy organizations frequently have resources and online publications about genetic conditions that provide information in understandable terms for patients and may also have publications written for health care professionals. Online resources that can be used to find support groups and resources for patients include: the Genetic Alliance (www.geneticalliance.org), Genetics Home Reference, the International Genetic Alliance (www.intga.org), National Organization for Rare Disorders (www.rarediseases.org) and Orphanet (www.orpha.net). The online directories of genetic testing laboratories discussed above also include links to support groups/resources. Patients can also benefit from referrals to local therapists.

CONCLUSIONS Genetic advances in identifying gene mutations associated with hereditary neurological and psychiatric conditions will make it possible for more individuals to learn about their risk status. Consulting with health care providers with genetics expertise can be beneficial in establishing/confirming a diagnosis, determining what genetic test to order, selecting a laboratory, and interpreting test results. Genetic counseling can help patients understand and adapt to living with a genetic condition, learn about implications for other relatives, make informed decisions about testing and care, and find out about support groups and resources. Given time constraints of typical clinic visits and potential to feel overwhelmed when confronted with a genetic condition, genetic counseling provides an opportunity for patients to be educated about their condition and discuss the psychosocial implications so that they have the information needed to make informed health care and life decisions.

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References 1. National Society of Genetic Counselors. http://nsgc.org/p/cm/ld/fid=175. 2. National Society of Genetic Counselors’ Definition Task Force, Resta R, Biesecker BB, Bennett RL, et al. A new definition of genetic counseling: National Society of Genetic Counselors’ Task Force Report. J Genet Couns. 2006;15:77–83. 3. Walker AP. The practice of genetic counseling. In: Uhlmann WR, Schuette JL, Yashar BM, eds. A Guide to Genetic Counseling. 2nd ed. New Jersey: John Wiley & Sons, Inc; 2009:1–35. 4. International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group on Huntington’s Chorea. Guidelines for the molecular genetics predictive test in Huntington’s disease. Neurology. 1994;44:1533–1536. 5. MacLeod R, Tibben A, Frontali M, et al. Editorial Committee and Working Group. ‘Genetic Testing Counselling’ of the European Huntington Disease Network. Recommendations for the predictive genetic test in Huntington’s disease. Clin Genet. 2013;83:221–231. 6. Goldman JS, Hahn SE, Catania JW, et al. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med. 2011;13:597–605. 7. Goldman JS. New approaches to genetic counseling and testing for Alzheimer’s disease and frontotemporal degeneration. Curr Neurol Neurosci Rep. 2012;12:502–510. 8. EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis, Andersen PM, Abrahams S, Borasio GD, et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS) – revised report of an EFNS task force. Eur J Neurol. 2012;19:360–375. 9. Chiò A, Battistini S, Calvo A, et al. The ITALSGEN Consortium. Genetic counseling in ALS: facts, uncertainties and clinical suggestions. J Neurol Neurosurg Psychiatry. 2014;85(5):478–485. 10. Quaid KA. Genetic counseling for frontotemporal dementias. J Mol Neurosci. 2011;45:706–709. 11. Uhlmann WR. Thinking it all through: case preparation and management. In: Uhlmann WR, Schuette JL, Yashar BM, eds. A Guide to Genetic Counseling. 2nd ed. New Jersey: John Wiley & Sons, Inc; 2009:93–131. 12. Uhlmann WR, Guttmacher AE. Key internet genetics resources for the clinician. JAMA. 2008;299:1356–1358. 13. Bennett RL, Steinhaus KA, Uhrich SB, et al. Recommendations for standardized human pedigree nomenclature: Pedigree Standardization Task Force of the National Society of Genetic Counselors. Am J Hum Genet. 1995;56:745–752. 14. Bennett RL, French KS, Uhrich SB, Resta RG, Doyle DL. Standardized human pedigree nomenclature: update and assessment of the recommendations of the National Society of Genetic Counselors. J Genet Counsel. 2008;17:424–433. 15. Uhlmann WR, Schuette JL, Yashar BM. A Guide to Genetic Counseling. 2nd ed. New Jersey: John Wiley & Sons, Inc; 2009. 16. Schaefer GB, Mendelsohn NJ. Professional Practice and Guidelines Committee. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med. 2013;15:399–407. 17. Sherman S, Pletcher BA, Driscoll DA. Fragile X syndrome: diagnostic and carrier testing. Genet Med. 2005;7:584–587. 18. Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST. Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med. 2011;13:680–685. 19. Richards CS, Bale S, Bellissimo DB, et al. Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee. ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet Med. 2008;10:294–300. 20. Rehm HL, Bale SJ, Bayrak-Toydemir P, et al. Working Group of the American College of Medical Genetics and Genomics Laboratory Quality Assurance Committee. ACMG clinical laboratory standards for next-generation sequencing. Genet Med. 2013;15:733–747. 21. Ross LF, Saal HM, David KL, Anderson RR. American Academy of Pediatrics, American College of Medical Genetics and Genomics. Technical report: ethical and policy issues in genetic testing and screening of children. Genet Med. 2013;15:234–245. 22. American Society of Human Genetics Social Issues Subcommittee on Familial Disclosure. ASHG statement. Professional disclosure of familial genetic information. Am J Hum Genet. 1998;62:474–483. 23. Hirschhorn K, Fleisher LD, Godmilow L, et al. Duty to re-contact. Genet Med. 1999;1:171–172. 24. Uhlmann WR. Ethical dilemmas. In: Lynch D, ed. Neurogenetics: Scientific and Clinical Advances. New York: Taylor & Francis; 2006:87–106. 25. Roberts JS, Uhlmann WR. Genetic susceptibility testing for neurodegenerative diseases: ethical and practice issues. Prog Neurobiol. 2013;110:89–101.

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