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familion LVNC Left Ventricular Noncompaction Cardiomyopathy ® Genetic Testing for Cardiovascular Disorders Gene Percentage of LVNC Inheritance Pattern ®MYH7 15% Autosomal LDB3 7% Autosomal Genetic Testing for Cardiovascular Disorders ACTC 3% Autosomal TAZ 3% X-linked TNNT2 2% Autosomal MYBPC3 Unknown Autosomal LMNA Unknown Autosomal familion LVNC is a Distinct Heritable Disorder The FAMILION LVNC Test • The FAMILION LVNC Test will identify a mutation in approximately 30% of patients with a high index of clinical suspicion for LVNC.3,6-13 • Genetic testing is the most reliable method for identifying potentially at-risk family members. – AHA/ACC/ESC, HFSA, and HRS/EHRA guidelines recommend family-specific testing after identifying a mutation-positive proband.14-16 Normal Heart Development • LVNC is thought to result from arrested myocardial morphogenesis preventing trabeculae from compacting.1,2 • Approximately 70% of LVNC is inherited.3 – LVNC shares a molecular etiology with HCM and DCM. Approximately 30% of LVNC patients have an identifiable mutation, which mostly occurs in genes encoding components of the cardiac sarcomere.1-4 Looping Trabeculations Compaction Clinically Diagnosing LVNC is Difficult • LVNC presents similarly to other cardiomyopathies and includes depressed systolic and diastolic function, systemic embolism, and arrhythmias. • Presently, there are no universally accepted criteria for diagnosing LVNC. Most criteria rely principally upon disease visualization, which may lead to a high rate of false-positive diagnoses.5 • Healthy, normal individuals can fulfill LVNC diagnostic criteria, underscoring the difficulty associated with diagnosing this disease. This is particularly true when trying to identify family members that may be at-risk.5 LVNC Heart Abnormal trabeculae References: 1. Maron BJ, Towbin JA, Thiene G, et al. Contemporary Definitions and Classification of the Cardiomyopathies. Cir- Transgenomic ® Advancing Personalized Medicine Five Science Park, New Haven CT 06511 Client Services 877.274.9432 • Fax 855.263.8668 www.familion.com Transgenomic and FAMILION are registered trademarks of Transgenomic, Inc. ©2014 Transgenomic, Inc. All rights reserved. Printed in USA. Document No. 602382 07/14 culation. 2006;113:1807-1816. 2. McNally E, Dellefave L. Sarcomere mutations in cardiogenesis and ventricular noncompaction. Trends Cardiovasc Med. 2009;19:17-21. 3. Hoedemaekers YM, Caliskan K, Majoor-Krakauer D et al. Cardiac b-myosin heavy chain defects in two families with non-compaction cardiomyopathy: linking non-compaction to hypertrophic, restrictive, and dilated cardiomyopathies. Eur. Heart J. 2007;28, 2732-2737. 4. Data on file, Transgenomic. 5. Kohli SK, Pantazis AA, et al. Diagnosis of left-ventricular non-compaction in patients with left-ventricular systolic dysfunction: time for a reappraisal of diagnostic criteria? Eur Heart Journ. 2008;29.89-95. 6. Klaassen S, Probst S, Oechslin E et al. Mutations in sarcomere protein genes in left ventricular noncompaction. Circulation. 2008;117, 2893-2901. 7. Xing Y, Ichida F, Matsuoka T et al. Genetic analysis in patients with left ventricular noncompaction and evidence for genetic heterogeneity. Mol. Genet. Metab. 2006;88, 71-77. 8. Ichida F, Tsubata S, Bowles KR et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation 2001;103, 1256-1263. 9. Vatta M, Mohapatra B, Jimenez S et al. Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction. J. Am. Coll. Cardiol. 2003;42, 2014-2027. 10. Hermida-Prieto M, Monserrat L, Castro-Beiras A et al. Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations. Am. J. Cardiol. 2004;94, 50-54. 11. Dellefave LM, Pytel P, Mewborn S et al. Sarcomere mutations in cardiomyopathy with left ventricular hypertrabeculation. Circ Cardiovasc Genet. 2009;2, 442-9. 12. Kenton AB, Sanchez X, Coveler KJ et al. Isolated left ventricular noncompaction is rarely caused by mutations in G4.5, a-dystrobrevin and FK binding protein-12. Mol. Genet. Metab. 2004;82, 162-166. 13 Chen R, Tsuji T, Ichida F et al. Mutation analysis of the G4.5 gene in patients with isolated left ventricular noncompaction. Mol. Genet. Metab. 2002;77, 319-325.14. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death—executive summary. J Am Coll Cardiol. 2006;48(5):1065-1102. 15. Hershberger RE, Lindenfeld J, Mestroni L, et al. Genetic evaluation of cardiomyopathy--a Heart Failure Society of America practice guideline. Journal of Cardiac Failure. 2009;15:83-97. 16. Ackerman MJ, Priori SG, Willems S, et al. HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies. Heart Rhythm. 2011;8:1308-39. familion ® document details the diagnostic, prognostic, and therapeutic implications provided by genetic test results for each of the diseases reviewed. A summary of selected recommendations is provided below. LVNC Summary of Expert on Genetic LeftConsensus VentricularRecommendations Noncompaction Cardiomyopathy Genetic Testing for Cardiovascular Disorders familion Testing for Channelopathies, Cardiomyopathies and SIDS/SUDS HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies ® Genetic Testing for Cardiovascular Disorders The Heart Rhythm Society (HRS) and European Heart Rhythm Association (EHRA) endorsed recommendations for genetic testing of cardiac channelopathies and cardiomyopathies. Authored by a writing group of international experts, the document details the diagnostic, prognostic, and therapeutic implications provided by genetic test results for each of the diseases reviewed. A summary of selected recommendations is provided below. Summary of Expert Consensus Recommendations on Genetic Testing for Channelopathies, Cardiomyopathies and SIDS/SUDS SIDS/ SUDS Cardiomyopathies Channelopathies Index Patients with Established or Suspected Clinical Diagnosis Recommended: For diagnosed/suspected patients or asymptomatic patients with idiopathic, serial QTc values >480 ms (prepuberty) or >500 ms (adults) LQTS Family Recommended May be considered: For asymptomatic patients with idiopathic, serial QTc values >460 ms (prepuberty) or >480 ms (adults) CPVT Recommended Recommended BrS Can be useful Recommended SQTS May be considered Recommended HCM Recommended Recommended Conduction Disease with DCM Recommended Recommended DCM Can be useful Recommended ARVC Can be useful: For patients satisfying 2010 task force diagnostic criteria May be considered: For patients with 1 major or 2 minor criteria Not recommended: For patients with only a single, minor criterion LVNC Can be useful Recommended Postmortem SIDS/SUDS May be considered: In the setting of autopsy-negative sudden unexplained death syndrome (SUDS) Recommended Transgenomic ® Advancing Personalized Medicine Five Science Park, New Haven CT 06511 Client Services 877.274.9432 • Fax 855.263.8668 www.familion.com Transgenomic and FAMILION are registered trademarks of Transgenomic, Inc. ©2014 Transgenomic, Inc. All rights reserved. Printed in USA. Document No. 602382 07/14 Recommended Reference and Table Adapted from: Ackerman MJ, Priori SG, Willems S, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm. 2011;8:1308-39.
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