Dilated Cardiomyopathy

Gene: PKP2

Green List (high evidence)

PMID: 30562116: reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.

PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).

PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.

Created: 7 Dec 2023, 1:58 a.m. | Last Modified: 7 Dec 2023, 1:59 a.m.

Panel Version: 1.23

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cardiomyopathy, MONDO:0004994, PKP2-related

Publications

• PMID: 30562116
• PMID: 35059364
• PMID: 38050058

Comment when marking as ready: Included due to phenotypic overlap between ARVC and DCM, limited evidence for association with DCM.

Created: 5 Aug 2020, 6:42 a.m. | Last Modified: 5 Aug 2020, 6:42 a.m.

Panel Version: 0.78

I don't know

Mutations in the PKP2 gene have been identified in individuals with arrhythmogenic right ventricular cardiomyopathy (ARVC). This condition most commonly affects the myocardium surrounding the right ventricle, one of the two lower chambers of the heart. ARVC increases the risk of an abnormal heartbeat (arrhythmia) and sudden death.

https://ghr.nlm.nih.gov/gene/PKP2
PMID:15489853, 16567567
https://doi.org/10.1371/journal.pone.0100560

ClinVar reports 1 variants only in an individual with DCM annotated as “LP” p.(His679Thr). No data regarding the variant associated with DCM is reported in GnomAD, supporting its low prevalence. However, if this is a variant linked to a clinical phenotype that initially manifested as ACM and then evolved into DCM is yet to be assessed. Considering that clinically cardiomyopathies are diseases with a progressive course, one cannot exclude that DCM cases carrying Pkp2 variants could be cases of advanced Arrythmogenic Cardiomyopathy (ACM or ARVC) which were missed in the initial disease phases. (https://doi.org/10.3389/fcvm.2018.00184)
Sources: Literature

Created: 5 Aug 2020, 6:39 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Arrhythmogenic right ventricular dysplasia 9 (MIM#609040)

Publications

• 15489853
• 16567567

Variants in this GENE are reported as part of current diagnostic practice