Dilated Cardiomyopathy Panel

Dilated cardiomyopathy (DCM) is a heterogeneous disease of the cardiac muscle. It is characterized by dilatation of the left, right, or both ventricles, systolic dysfunction, and diminished myocardial contractility. Symptoms include arrhythmia, dyspnea, chest pain, palpitation, fainting, and congestive heart failure (Ikram et al. 1987). Additional features may include conduction defects, woolly hair, and skeletal myopathy (Møller et al. 2009). Although symptoms of DCM usually begin in adulthood, an extensive clinical variability between individuals concerning the age of onset, penetrance, and extent of structural and functional abnormality has been documented. The prevalence of DCM has been estimated at ~1/2700 (Codd et al. 1989), but it could be 10-folder higher as proposed by another study (Hershberger et al. 2013). Up to 50% of DCM cases are classified as idiopathic and 30-50% of idiopathic DCM cases are inherited and termed Familial Dilated cardiomyopathy (FDCM) (Felker et al. 2000; de Gonzalo-Calvo et al. 2017). For additional information see GeneReviews (Hershberger and Morales 2013).

DCM is genetically heterogeneous disease and most commonly inherited in an autosomal dominant manner. However, other modes of inheritance have been described, such as autosomal recessive (FKTN and GATAD1); X-linked recessive (DMD, EMD and TAFAZZIN), and X-linked dominant (LAMP2). The DCS2, DSP, LMNA, SCN5A, TCAP*, TNNI3 and TTN genes are associated with autosomal dominant and recessive disorders. (OMIM; Human Gene Mutation Database, *limited cases). See individual gene test descriptions for information on molecular biology of gene products.

This panel can detect pathogenic variants in 35-40% of patients with Familial Dilated Cardiomyopathy (Hershberger et al. 2013; McNally et al. 2013).

Gross deletions or duplications not detectable by Sanger sequencing have been reported in CAV3, DES, DSP, NKX2-5, PKP2, and SCN5A as individual cases (Human Gene Mutation Database).

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 98.1% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).