Left ventricular non-compaction cardiomyopathy (LVNC)

LVNC-associated genetic disorders exhibit heterogeneous inheritance patterns. Autosomal dominant inheritance is most common, although autosomal recessive, X-linked, and mitochondrial forms have also been reported. The mode of inheritance depends on the underlying genetic condition and should be established for the specific gene-disease relationship to support appropriate risk assessment and genetic counselling of relatives.

• Where LVNC is suspected to have a genetic basis, molecular genetic testing may help identify the underlying condition and confirm the clinical diagnosis. Genetic testing is particularly informative in patients with familial disease, associated cardiomyopathy, extracardiac manifestations, or syndromic features.
• Establishing the genetic diagnosis may contribute to risk stratification, clinical management, and surveillance planning depending on the underlying disorder.
• Identification of a pathogenic germline variant enables predictive genetic testing of at-risk relatives and supports genetic counselling, including reproductive counselling where appropriate.
• Genetic testing is generally not indicated for isolated incidental LVNC morphology in individuals with normal left ventricular function, no syndromic features, and no relevant family history.

• Sedaghat-Hamedani F, Haas J, Zhu F, Geier C, Kayvanpour E, Liss M, et al. Clinical genetics and outcome of left ventricular non-compaction cardiomyopathy. Eur Heart J. 2017;38(46):3449-60. doi:10.1093/eurheartj/ehx545. PMID:.
• Schaefer E, Helms P, Marcellin L, Desprez P, Billaud P, Chanavat V, et al. Next-generation sequencing (NGS) as a fast molecular diagnosis tool for left ventricular noncompaction in an infant with compound mutations in the MYBPC3 gene. Eur J Med Genet. 2014;57(4):129-32. doi:10.1016/j.ejmg.2014.02.015. PMID:.
• Probst S, Oechslin E, Schuler P, Greutmann M, Boyé P, Knirsch W, et al. Sarcomere gene mutations in isolated left ventricular noncompaction cardiomyopathy do not predict clinical phenotype. Circ Cardiovasc Genet. 2011;4(4):367-74. doi:10.1161/CIRCGENETICS.110.959270. PMID:.
• Llerena-Velastegui J, Lopez-Usina A, Mantilla-Cisneros C. Prevalence, clinical manifestations, and adverse outcomes of left ventricular noncompaction in adults: a systematic review and meta-analysis. Cardiol Res. 2024;15(5):377-95. doi:10.14740/cr1673. PMID:; PMCID:PMC11483115.
• Cannie D, Elliott P. The genetics of left ventricular noncompaction. Curr Opin Cardiol. 2021;36(3):301-8. doi:10.1097/HCO.0000000000000844. PMID:.
• Arbelo E, Protonotarios A, Gimeno JR, Arbustini E, Barriales-Villa R, Basso C, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J. 2023;44(37):3503626. doi:10.1093/eurheartj/ehad194. PMID:.
• Wilde AAM, Semsarian C, Márquez MF, Shamloo AS, Ackerman MJ, Ashley EA, et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases. Europace. 2022;24(8):1307-67. doi:10.1093/europace/euac030. PMID:; PMCID:PMC9435643.
• Casas G, Rodríguez-Palomares JF, Ferreira-González I. Left ventricular noncompaction: a disease or a phenotypic trait? Rev Esp Cardiol (Engl Ed). 2022;75(12):1059-69. doi:10.1016/j.rec.2022.07.002. PMID:.