肥厚性心肌病的遗传筛查课件

Genetic Evaluation of Cardiomyopathy HFSA 2010 Recommendations New Section Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline Genetic EvaluationFamily History Recommendation 17.1 A careful family history for 3 generations is recommended for all patients with cardiomyopathy. Hypertrophic cardiomyopathy Strength of Evidence = A Dilated cardiomyopathy Strength of Evidence = A Arrhythmogenic right ventricular dysplasia Strength of Evidence = A Left ventricular noncompaction Strength of Evidence = A Restrictive cardiomyopathy Strength of Evidence = B Cardiomyopathies associated with extracardiac manifestations Strength of Evidence = A Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline Genetic EvaluationClinical Screening Recommendation 17.2.a Clinical screening for cardiomyopathy in asymptomatic first- degree relatives is recommended. a. Cardiomyopathy phenotype: Hypertrophic cardiomyopathy Strength of Evidence = A Dilated cardiomyopathy Strength of Evidence = A Arrhythmogenic RV dysplasia Strength of Evidence = A Left ventricular noncompaction Strength of Evidence = B Restrictive cardiomyopathy Strength of Evidence = B Cardiomyopathies associated with extracardiac manifestations Strength of Evidence = A Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline Genetic EvaluationClinical Screening Recommendation 17.2.b and c b. Clinical screening for cardiomyopathy is recommended at intervals (see 17.2.e) in asymptomatic at-risk relatives who are known to carry the disease-causing mutations. Strength of Evidence = A c. Clinical screening for cardiomyopathy is recommended for asymptomatic at-risk first- degree relatives when genetic testing has not been performed or has not identified a disease- causing mutation. Strength of Evidence = A Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline Genetic EvaluationClinical Screening Recommendation 17.2.d d. It is recommended that clinical screening consist of: History (with special attention fo HF symptoms, arrhythmias, presyncope and syncope) Physical examination (with special attention to the cardiac and skeletal muscle systems) Electrocardiogram and echocardiogram CK-MM (at initial evaluation only) Signal-averaged electrocardiogram (SAECG) in ARVD only Holter monitoring in HCM, ARVD Exercise treadmill testing in HCM MRI in ARVD Strength of Evidence = B Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline Cardio- myopathy Phenotype Interval if genetic testing or family screening is negative Screening interval if a mutation is present Strength of Evidence HypertrophicEvery 3 yrs until age 30; yearly during puberty; after 30, if symptoms Every 3 yrs age 30; yrly during puberty; every 5 yrs thereafter B DilatedEvery 3-5 yrs beginning in childhood Yearly in childhood; every 1-3 yrs in adlts. B ARVD/CEvery 3-5 yrs after age 10Yearly ages 10- 50C LVNCEvery 3 yrs beginning in childhood Yearly in childhood; every 1-3 yrs in adlts. C RestrictiveEvery 3-5 years beginning in adults Yearly in childhood; every 1-3 yrs in adlts. C Recommendation 17.2.e. Clinical screening for cardiomyopathy should be considered at the following times and intervals or at any time signs or symptoms appear. Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline Genetic EvaluationClinical Screening Recommendation 17.2.f f. At-risk first-degree relatives with any abnormal clinical screening tests (regardless of genotype) should be considered for repeat clinical screening at 1 year. Strength of Evidence = C Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline Genetic EvaluationReferral Recommendation 17.3 Evaluation, genetic counseling, and genetic testing of cardiomyopathy patients are complex processes. Referral to centers expert in genetic evaluation and family-based management should be considered. Strength of Evidence = B Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline Genetic EvaluationTesting Recommendation 17.4.a Genetic testing should be considered for the one most clearly affected person in a family to facilitate family screening and management. a. Cardiomyopathy phenotype: Hypertrophic cardiomyopathy Strength of Evidence = A Dilated cardiomyopathy Strength of Evidence = B Arrhythmogenic RV dysplasia Strength of Evidence = A Left ventricular noncompaction Strength of Evidence = C Restrictive cardiomyopathy Strength of Evidence = C Cardiomyopathies associated with extracardiac manifestations Strength of Evidence = A Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline PhenotypeGene Tests AvailableYield of Positive Results Hypertrophic (HCM) MYH7, MYBPC7, TNNT2, TNNI3, TPMI, ACTC, MYL2, MYL3 MYH7, MYBPC3 = 60-80% of mutations, TNNT2 = 10-20%. Genetic cause identifiable in 35-45% overall. If family history is positive, 60-65% Dilated (DCM) LMNA,MYH7, TNNT2, SCN5A, DES, MYBPC3, TNNI3, TPMI, ACTC, PLN, LDB3, TAZ LMNA = 5.5%, MYH7 = 4.2%, TNNT2 = 2.9%. All data from research cohorts ARVD/CDSP, PKP2, DSG2, DSC2DSP = 6-16%, PKP2 = 11-43%, DSG2 = 12-40% LVNCUncertainUncertain RestrictiveUncertainUncertain Recommendation 17.4.b. Specific genes available for screening based on cardiac phenotype Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline Genetic EvaluationTesting GeneTests () An NIH-funded resource that lists clinical (and research) molecular genetic testing laboratories for the cardiomyopathies. Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline Genetic EvaluationTesting Recommendation 17.4.c Screening for Fabry disease is recommended in all men with sporadic or non-autosomal dominant (no male-to- male) transmission of unexplained cardiac hypertrophy. Strength of Evidence = B Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline Genetic EvaluationCounseling Recommendation 17.5 Genetic and family counseling is recommended for all patients and families with cardiomyopathy. Strength of Evidence = A Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194. HFSA 2010 Practice Guideline Genetic EvaluationMedical