Advertisement

Family Screening: Who, When and How

  • Michelle Michels
  • Folkert J. ten Cate
Chapter

Abstract

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant familial 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 the cardiologist and the clinical geneticist. 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 regards 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.

Keywords

Hypertrophic cardiomyopathy Familial screening Genetic counseling Genetic testing Electrocardiogram Echocardiogram 

References

  1. 1.
    Hollman A, Goodwin JF, Teare D, Renwick JW. A family with obstructive cardiomyopathy (asymmetrical hypertrophy). Br Heart J. 1960;22:449–56.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Gersh BJ, Maron BJ, Bonow RO, Dearini JA, Fifer MA, Link MS, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hyperthrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011;25:e212–60.CrossRefGoogle Scholar
  3. 3.
    Maron BJ. Sudden death in young athletes. N Engl J Med. 2003;349:1064–75.PubMedCrossRefGoogle Scholar
  4. 4.
    Corrado D, Basso C, Schiavon M, Thiene G. Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med. 1998;339:364–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Corrada D, Pelliccia A, Bjornstad HH, Vanhees L, Biffi A, Borjesson M, et al. Cradiovascular pre-participation screening of young competitive athletes for prevention of sudden cardiac death: proposal for a common European protocol. Eur Heart J. 2005;26:516–24.CrossRefGoogle Scholar
  6. 6.
    Bjornstad H, Corrado D, Pelliccia A. Prevention of sudden death in young athletes: a milestone in the history of sports cardiology. Eur J Cardiovasc Prev Rehabil. 2006;13:857–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Schinkel AF, Vriesendorp PA, Sijbrands EJ, Jordaens LJ, ten Cate FJ, Michels M. Outcome and complications after implantable cardioverter defibrillator therapy in hypertrophic cardiomyopathy: systematic review and meta-analysis. Circ Heart Fail. 2012;5:552–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies. Heart Rhythm. 2011;8:1308–39.PubMedCrossRefGoogle Scholar
  9. 9.
    Andreasen C, Nielsen JB, Refsgaard L, Holst AG, Christensen AH, Andreasen L, et al. New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. Eur J Hum Genet. 2013;21:918–28.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Van Maarle MC, Stouthard ME, Marang-van de Meen PJ, Klazinga NS, Bonsel GJ. How disturbing it is to be approached for a genetic cascade screening programme for familial hypercholesteremia? Community Genet. 2001;4:244–52.PubMedCrossRefGoogle Scholar
  11. 11.
    Ingles J, Sarina T, Yeates L, Hunt L, Macciocca I, McCormack L, et al. Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy. Genet Med. 2013;15:972–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Maron BJ, Maron MS, Semsarian C. Genetics of hypertrophic cardiomyopathy after 20 years. J Am Coll Cardiol. 2012;60:705–15.PubMedCrossRefGoogle Scholar
  13. 13.
    Hallowell N, Jenkins N, Douglas M, Walker S, Porteous M, et al. Patients’ experiences and views of cascade screening for familial hypercholesterolemia (FH): a qualitative study. J Community Genet. 2011;2:249–57.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Wordsworth S, Leal J, Blair E, Legood R, Thomson K, Seller A. DNA testing for hypertrophic cardiomyopathy: a cost-effectiveness model. Eur Heart J. 2010;31:926–35.PubMedCrossRefGoogle Scholar
  15. 15.
    Abiola S. Recent developments in health law. The Genetic Information Nondiscrimination Act of 2008. J Law Med Ethics. 2008;36:856–60.PubMedCrossRefGoogle Scholar
  16. 16.
    Jensen MK, Havndrup O, Christiaensen M, Andersen PS, Diness B, Axelsson A, et al. Penetrance of hypertrophic cardiomyopathy in children and adolescents. Circulation. 2013;127:48–54.PubMedCrossRefGoogle Scholar
  17. 17.
    Ormondroyd E, Oates S, Parker M, Blair E, Watkins H. Pre-symptomatic genetic testing for inherited cardiac conditions: a qualitative exploration of psychological and ethical implications. Eur J Hum Genet. 2014;22:88–93.PubMedCrossRefGoogle Scholar
  18. 18.
    Krul SPJ, van der Smagt JJ, van de Berg MP, Sollie KM, Pieper PG, van Spaendonck-Zwarts KY. Systematic review of pregnancy in women with inherited cardiomyopathies. Eur J Heart Fail. 2011;13:584–94.PubMedCrossRefGoogle Scholar
  19. 19.
    Bratt EL, Ostman-Smith I, Axelsson A, Berntsson L. Quality of life in asymptomatic children and adolescents before and after diagnosis of hypertrophic cardiomyopathy through family screening. J Clin Nurs. 2012;22:211–2.PubMedCrossRefGoogle Scholar
  20. 20.
    Christiaans I, van Langen IM, Birnie E, Bonsel GJ, Wilde AA, Smets EM. Quality of life and psychological distress in hypertrophic cardiomyopathy. Am J Med Genet. 2009;149A:602–12.PubMedCrossRefGoogle Scholar
  21. 21.
    Moak JP, Kaski JP. Hypertrophic cardiomyopathy in children. Heart. 2012;98:1044–54.PubMedCrossRefGoogle Scholar
  22. 22.
    Delcrè SDL, DiDonna P, Leuzzi S, Miceli S, Bisi M, Scaglione M, et al. Relationship of ECG findings to phenotypic expression in patients with hypertrophic cardiomyopathy: a cardiac magnetic resonance study. Int J Cardiol. 2013;167:1038–45.PubMedCrossRefGoogle Scholar
  23. 23.
    Maron BJ. The electrocardiogram as a diagnostic tool for hypertrophic cardiomyopathy: revisited. Ann Noninvasive Electrocardiol. 2001;6:277–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Ryan MP, Cleland JG, French JA, Joshi J, Choudhury L, Chojnowska L. The standard electrocardiogram as a screening test for hypertrophic cardiomyopathy. Am J Cardiol. 1995;76:689–94.PubMedCrossRefGoogle Scholar
  25. 25.
    Lakdawala NK, Thune JJ, Maron BJ, Cirino AL, Havndrup O, Bundgaard H, et al. Electrocardiographic features of sarcomere mutation carriers with and without clinically overt hypertrophic cardiomyopathy. Am J Cardiol. 2011;108:1606–13.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    McKenna WJ, Spirito P, Desnos M, Dubourg O, Komajda M. Experience form clinical genetics in hypertrophic cardiomyopathy: proposal for new diagnostic criteria in adult members of affected families. Heart. 1997;77:130–2.PubMedCentralPubMedGoogle Scholar
  27. 27.
    Eriksson MJ, Sonnenberg B, Woo A, Rakowski P, Parker TG, Wigle D, et al. Long-term outcome in patients with apical hypertrophic cardiomyopathy. J Am Coll Cardiol. 2002;39:638–45.PubMedCrossRefGoogle Scholar
  28. 28.
    Spindler M, Saupe KW, Christe ME, Sweeney HL, Seidman CE, Seidman JG, et al. Diastolic dysfunction and altered energetics in the alphaMHC403/+mouse model of familial hypertrophic cardiomyopathy. J Clin Invest. 1998;101:1775–83.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Nagueh SF, Bachinski LL, Meyer D, Hill R, Zoghbi WA, Tam JW, et al. Tissue Doppler imaging consistently detects myocardial abnormalities in patients with hypertrophic cardiomyopathy and provides novel means for an early diagnosis before and independently of hypertrophy. Circulation. 2001;104:128–30.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Ho CY, Sweitzer NK, McDonough B, Maron BJ, Casey SA, Seidman JG, et al. Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy. Circulation. 2002;105:2992–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Michels M, Soliman OI, Kofflard MJ, Hoedemaekers YM, Dooijes D, Majoor-Krakauer D, et al. Diastolic abnormalities as the first feature of hypertrophic cardiomyopathy in Dutch myosin-binding protein C founder mutations. JACC Cardiovasc Imaging. 2009;2:58–64.PubMedCrossRefGoogle Scholar
  32. 32.
    Valente AM, Lakdawala NK, Powell AJ, Evans SP, Cirino MS, Orav EJ, et al. Comparison of echocardiographic and cardiac magnetic resonance imaging in hypertrophic cardiomyopathy sarcomere mutation carriers without left ventricular hypertrophy. Circ Cardiovasc Genet. 2013;6:230–7.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Harrigan CJ, Appelbaum E, Maron BJ, Buros JL, Gibson CM, Lesser JR, et al. Significance of papillary muscle abnormalities identified by cardiovascular magnetic resonance in hypertrophic cardiomyopathy. Am J Cardiol. 2008;101:668–73.PubMedCrossRefGoogle Scholar
  34. 34.
    Maron MS, Olivotto I, Harrigan C, Appelbaum E, Gibson CM, Lesser JR, et al. Mitral valve abnormalities identified by cardiovascular magnetic resonance represent a primary phenotypic expression of hypertrophic cardiomyopathy. Circulation. 2011;124:40–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Germans T, Wilde AA, Dijkmans PA, Chai W, Kamp O, Pinto YM, et al. Structural abnormalities of the inferoseptal left ventricular wall detected by cardiac magnetic resonance imaging in carriers of hypertrophic cardiomyopathies mutations. J Am Coll Cardiol. 2006;48:2518–23.PubMedCrossRefGoogle Scholar
  36. 36.
    Maron MS, Rowin EJ, Lin D, Appelbaum E, Chan RH, Gibson M, et al. Prevalence and clinical profile of myocardial crypts in hypertrophic cardiomyopathy. Circ Cardiovasc Imaging. 2012;5:441–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Rowin EJ, Maron MS, Lesser JR, Maron BJ. CMR with late gadolinium enhancement in genotype positive-phenotype negative hypertrophic cardiomyopathy. JACC Cardiovasc Imaging. 2012;5:119–22.PubMedCrossRefGoogle Scholar
  38. 38.
    Christiaans I, Lekanne dit Deprez RH, Van Langen I, Wilde AAM. Ventricular fibrillation in MYH7-related hypertrophic cardiomyopathy before the onset of ventricular hypertrophy. Heart Rhythm. 2009;6:1366–9.PubMedCrossRefGoogle Scholar
  39. 39.
    O’Hanlon R, Grasso A, Rougthon M, Moon JC, Clark S, Wage R, et al. Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2010;56:867–74.PubMedCrossRefGoogle Scholar
  40. 40.
    Chan RH, Maron B, Olivotto I, Assenza G, Hong S, Lesser J, et al. Prognostic utility of contrast-enhanced cardiovascular magnetic resonance in hypertrophic cardiomyopathy: a multicenter study. JACC. 2012;59:E1570 (abstract).Google Scholar
  41. 41.
    Christiaans I, Birnie E, Bonsel GJ, Mannens MM, Michels M, Majoor-Krakauer D, et al. Manifest disease, risk factors for sudden cardiac death, and cardiac events in a large nationwide cohort of predictively tested hypertrophic cardiomyopathy mutation carriers: determining the best cardiological screening strategy. Eur Heart J. 2011;32:1161–70.PubMedCrossRefGoogle Scholar
  42. 42.
    Michels M, Soliman OI, Phefferkorn J, Hoedemaekers YM, Kofflard MJ, Dooijes D, et al. Disease penetrance and risk stratification for sudden cardiac death in asymptomatic hypertrophic cardiomyopathy mutation carriers. Eur Heart J. 2009;30:2593–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Ho CY, Lopez B, Coelho-Filho OR, Lakdawala NK, Cirino AL, Jarolim P, et al. Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy. N Engl J Med. 2010;363:552–63.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Maron BJ, Zipes DP. 36th Bethesda conference: eligibility recommendations for competitive athletes with cardiovascular abnormalities. J Am Coll Cardiol. 2005;45:1312–75.CrossRefGoogle Scholar
  45. 45.
    Pelliccia A, Corrado D, Bjornstad HH, Panhuyzen-Goedkoop N, Urhausen A, Carre F, et al. Recommendations for participation in competitive sport and leisure-time activity in individuals with cardiomyopathies, myocarditis and pericarditis. Eur J Cardiovasc Prev Rehabil. 2006;13:876–85.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2015

Authors and Affiliations

  1. 1.Department of CardiologyErasmus MC HospitalRotterdamThe Netherlands

Personalised recommendations