Non-compaction cardiomyopathy is a clinically heterogeneous disease, which is characterized by the presence of excessively prominent trabeculations in the myocardium accompanied by crypts and a very thin layer of compacted heart muscle. Mutations in genes that are associated with other types of cardiomyopathies (particularly hypertrophic and dilated) can cause this pathology. However, genes specifically related to non-compaction cardiomyopathy have also been described.
The progression of the disease may present deteriorating cardiac function with the development of cardiac insufficiency, as well as malignant arrhythmias, and thus early diagnosis is important. Genetic testing is useful since:
- It is able to identify the causative mutation, confirming the diagnosis of the disease. Due to the clinical heterogeneity with much overlap between different phenotypes, it is very important for differential diagnosis.
- When a pathogenic mutation is detected, it can be used as a predictive test. It is useful in genetic counseling, since it can detect carriers at risk who should undergo adequate clinical monitoring.
- Rapezzi C, et al. Diagnostic work-up in cardiomyopathies: Bridging the gap between clinical phenotypes and final diagnosis. A position statement from the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013;34(19):1448-1458. (doi:10.1093/eurheartj/ehs397
- Charron P, Arad M, Monserrat L, et al. Genetic counselling and testing in cardiomyopathies: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2010;31(22):2715-2728.
The probability of identifying a likely causative mutation in a patient under suspicion of non-compaction cardiomyopathy varies due to the clinical heterogeneity of the disease. The diagnostic yield is higher in cases with a clear phenotype and family history of the disease. It is generally about 50%.
Non-compaction Cardiomyopathy Panel
This panel is indicated as a first diagnostic approach in patients with a clear phenotype of non-compaction cardiomyopathy. It is a panel designed specifically for this pathology. It includes priority genes, which are genes that have been clearly associated with the disease. Some of them are also associated with other cardiomyopathies. Genes that have been sporadically associated with the disease are listed as secondary genes, and candidate genes gathered from a systematic literature review are also included.
ACTC1, MYBPC3, MYH7, TAZ, ACTN2, DMD, DNAJC19, DTNA, FHL1, HCN4, LDB3, LMNA, MIB1, MYH6, MYL2, NKX2-5, PLN, PRDM16, RYR2, TNNT2, TPM1, ANKRD1*, BAG3*, CASQ2*, CSRP3*, DSP*, FLNC*, KCNH2*, KCNQ1*, MLYCD*, MYL3*, NOTCH1*, PTPN11*, TNNC1*, TNNI3*, TTN*
Other Panels that Include this Diagnosis
Notes on Genes:
Priority Genes: These genes include >70% of the mutations that have been previously associated with the development of non-compaction cardiomyopathy and/or their testing is recommended by the guidelines. Secondary genes: Other genes related to the disease. *Candidate genes: Without evidence but potentially related to the phenotype.