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Family Screening: Who, When, and How

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Hypertrophic Cardiomyopathy

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Abstract

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant cardiac disease. The most devastating presentation of HCM is SCD in a presumed healthy person. The goals of family screening are to identify relatives with unrecognized HCM and to follow at-risk individuals for risk factors of SCD and disease development.

After confirmation of the HCM diagnosis, the patient is informed about the familial character of the disease, the high potential for familial transmission, and the possibility to perform genetic testing. Currently the power of genetic testing in HCM lies in identifying family members carrying the genotype (G+) who are at risk for developing disease and excluding unaffected, genotype-negative relatives for further cardiac evaluation.

In specialized cardio-genetic outpatient clinics, familial and genetic counseling is performed in close collaboration between cardiologists and the clinical geneticists. Family members at risk are identified, and first-degree relatives are informed either via the patient or via direct communication. It is important that ramifications of genetic and/or cardiac testing, especially with regard to health and life insurance, are explained to the family members prior to analysis.

G+ family members and family members of HCM families in which no pathogenic mutation is found are offered longitudinal cardiac evaluation by electrocardiogram and echocardiogram with variable intervals.

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Author information

Authors and Affiliations

  1. Erasmus MC, Rotterdam, CA, The Netherlands

    Michelle Michels

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  1. Michelle Michels
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Corresponding author

Correspondence to Michelle Michels .

Editor information

Editors and Affiliations

  1. Westchester Medical Center, Valhalla, NY, USA

    Srihari S. Naidu

Questions

Questions

  1. 1.

    At what age should family screening in hypertrophic cardiomyopathy in first-degree relatives be started?

    1. A.

      After birth

    2. B.

      At the age of 18 years

    3. C.

      At the age of 30 years

    4. D.

      At the age of 10 years

    5. E.

      At the age of 4 years

  • The correct answer is D:

  • Current European guidelines advise to start with family screening at the age of 10, earlier screening is only advised in special circumstances (malignant family history, if the child is a competitive athlete or when there are other signs or symptoms of early HCM).

  1. 2.

    Hypertrophic cardiomyopathy is an inheritable cardiac disease. What is the change of transmission of the disease to offspring?

    1. A.

      10%

    2. B.

      50%

    3. C.

      25%

    4. D.

      5%

  • The correct answer is B:

  • Hypertrophic cardiomyopathy is inherited in an autosomal dominant manner, this implicates that every child of a HCM patient has a 50% chance of inheriting the disease.

  1. 3.

    Is repeated cardiac evaluation advised in relatives at risk for HCM?

    1. A.

      Yes, cardiac evaluation is recommended with regular intervals until the age of 24 years.

    2. B.

      No, one cardiac evaluation is sufficient in adult relatives at risk if there are no abnormalities found.

    3. C.

      Yes, “lifelong” cardiac evaluation is recommended in at-risk relatives with regular intervals.

    4. D.

      Yes, cardiac evaluation is recommended with regular intervals between the age of 10 and 40 years old.

  • The correct answer is C:

  • HCM is characterized by age-related penetrance; this means that cardiac evaluation should be repeated with regular intervals until advanced age.

  1. 4.

    Which examinations are advised in the cardiac evaluation of all at-risk relatives?

    1. A.

      Transthoracic echocardiogram and electrocardiogram

    2. B.

      Transthoracic echocardiogram, electrocardiogram, and Holter monitoring

    3. C.

      Transthoracic echocardiogram and cardiac magnetic resonance imaging

    4. D.

      Cardiac magnetic resonance imaging, electrocardiogram, and Holter monitoring

  • The correct answer is A:

  • Cardiac evaluation of at-risk relatives starts with an electrocardiogram and echocardiogram; if (subtle) abnormalities are detected, further cardiac evaluation including cardiac magnetic resonance imaging, Holter monitoring, and exercise testing should be done.

  1. 5.

    What should you advise in a genotype-positive/phenotype-negative subject who wants to participate in competitive sport?

    1. A.

      Genotype-positive/phenotype-negative subjects should be excluded from all competitive sports.

    2. B.

      Genotype-positive/phenotype-negative subjects can only perform low-intensity sporting activities.

    3. C.

      Genotype-positive/phenotype-negative subjects can enroll in competitive sports after extensive negative cardiac investigation.

  • The correct answer is C:

  • At present, the reported SCD rate in G+/LVH− subjects is extremely low, and therefore both the AHA/ACC and ESC recommendations don’t advise to routinely exclude G+/LVH− subjects from competitive sports. If the results of extensive cardiac investigations, including cardiac magnetic resonance imaging, Holter monitoring, and exercise testing are normal, subjects can enroll in competitive sports with regular, i.e., yearly, evaluation.

  1. 6.

    What are the advantages of presymptomatic genetic testing in first-degree relatives of a HCM patient with a definitive mutation?

    1. A.

      The advantages of presymptomatic genetic testing are identifying genotype-positive family members at risk of HCM and reassuring genotype-negative relatives.

    2. B.

      The advantages of presymptomatic genetic testing are identifying genotype-positive family members and prediction of the disease development and prognosis of HCM.

    3. C.

      There are no advantages of presymptomatic genetic testing.

  • The correct answer is A:

  • Currently, the power of HCM mutational analysis lies most prominently in identifying G+ family members who are at risk for developing disease and excluding unaffected, genotype-negative (G-) relatives of further cardiac evaluation; this is information not achievable otherwise. Given the extensive clinical heterogeneity of HCM, individual prognostic prediction is mainly based on the phenotype found.

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Michels, M. (2019). Family Screening: Who, When, and How. In: Naidu, S. (eds) Hypertrophic Cardiomyopathy. Springer, Cham. https://doi.org/10.1007/978-3-319-92423-6_14

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  • DOI: https://doi.org/10.1007/978-3-319-92423-6_14

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  • Publisher Name: Springer, Cham

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  • Online ISBN: 978-3-319-92423-6

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