Diagnostics

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Dilated Cardiomyopathy Panel

The Dilated Cardiomyopathy Panel is a comprehensive NGS panel that can be used to confirm a clinical diagnosis of dilated cardiomyopathy or identify at-risk individuals. Dilated cardiomyopathy is characterized by enlargement of the left ventricle,systolic dysfunction, and reduction of the heart’s contractile force over time. Patients may experience heart failure, arrhythmias, reduced cardiac output, and thromboembolic disease, including stroke. The condition increases a person’s risk for sudden cardiac death, even in the absence of other symptoms.

Prevalence

The prevalence of arrhythmogenic right ventricular cardiomyopathy is estimated to be 1 in 1,000 to 1 in 1,250 individuals (Peters, 2006).

Included Disorders

This panel includes genes related to primary dilated cardiomyopathy as well as genes associated with disorders that include dilated cardiomyopathy as a feature. These disorders include::

  • Arrhythmogenic right ventricular cardiomyopathy
  • Emery-Dreifuss muscular dystrophy
  • Duchenne and Becker muscular dystrophy
  • Hypertrophic cardiomyopathy
  • Transthyretin (TTR) amyloidosis
  • Danon disease
  • Left ventricular noncompaction

Inheritance and Penetrance

The majority of familial dilated cardiomyopathy is inherited in an autosomal dominant manner, although in some cases it is inherited in an X-linked or recessive manner. Onset of dilated cardiomyopathy is typically in the fourth to sixth decade of life, although the disease may present at any time. Mutations causing familial dilated cardiomyopathy demonstrate age-related and reduced penetrance, as well as variable expressivity (Hershberger and Siegfried, 2011).

Clinical Sensitivity

Disease causing mutations can be identified in approximately 40% of familial dilated cardiomyopathy (Hershberger et al, 2013). The dilated cardiomyopathy comprehensive panel includes all of the common genetic causes of dilated cardiomyopathy.

Methodology and Analytical Sensitivity

Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent intron/exon boundaries, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering. Analytical sensitivity of the assay is 99.5%.

Indications for Testing

  • Confirmation of a clinical diagnosis
  • Unexplained cardiac arrest
  • Risk assessment for asymptomatic family of members of proband with molecular diagnosis of dilated cardiomyopathy

Included Genes (42)

ABCC9 DSG2 MYBPC3 TCAP
ACTC1 DSP MYH7 TMEM43
ACTN2 EMD PKP2 TNNC1
BAG3 EYA4 PLN TNNI3
CAV3 FKRP RAF1 TNNT2
CRYAB FKTN RBM20 TPM1
CSRP3 FLNC RYR2 TTN
DES JUP SCN5A TTR
DMD LAMP2 SGCD VCL
DOLK LDB3 SLC22A5
DSC2 LMNA TAZ

Additions to Dilated Cardiomyopathy Panel

Emerging Evidence Genes (20)

Emerging evidence genes can also be added on to the Dilated Cardiomyopathy Panel. These genes do not have a clear association with dilated cardiomyopathy, but emerging evidence suggests that they may play a role in disease:

ANKRD1 GATA6 MYH6 NPPA
CHRM2 GATAD1 MYPN PLEKHM2
CTF1 ILK NEBL PDLIM3
FHL2 LAMA4 NEXN TMPO
GATA4 LRRC10 NKX2-5 TXNRD2

Syndromic Pediatric Add-On Panel

Syndromic Pediatric Onset Genes (6):

 

Genes associated with pediatric onset, syndromic, autosomal recessive disorders with dilated cardiomyopathy as feature can also be added to the Dilated Cardiomyopathy Panel.

ACADVL ALMS1 CPT2 DNAJC19 SDHA TMEM70

References

  1. Codd MB, Sugrue DD, Gersh BJ, Melton LJ 3rd. Epidemiology of idiopathic dilated and hypertrophic cardiomyopathy. A population-based study in Olmsted County, Minnesota, 1975-1984. Circulation. 1989;80:564–72.
  2. Hershberger RE, Hedges DJ, Morales A. Dilated cardiomyopathy: the complexity of a diverse genetic architecture. Nat Rev Cardiol. 2013;10:531–47.
  3. Hershberger RE, Siegfried JD. Update 2011: clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol. 2011;57(16):1641-9.