Paediatric or syndromic cardiomyopathy

Gene: DSG2

Green List (high evidence)

Comment on mode of inheritance: There are at least three unrelated cases reported with childhood/ juvenile onset cardiomyopathy. Hence, the MOI can be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal ' in the next GMS update.

Created: 4 Sep 2026, 5:56 p.m. | Last Modified: 4 Sep 2026, 5:56 p.m.

Panel Version: 8.14

Monoallelic variants in this gene has been associated with arrhythmogenic right ventricular cardiomyopathy in OMIM (MIM #610193), ClinGen (with 'Definitive' rating by Arrhythmogenic Right Ventricular Cardiomyopathy GCEP) and Gene2Phenotype (with definitive rating on the Cardiac panel) and all these records were last accessed on 04 September 2026. However, biallelic variants are associated with DSG2-related arrhythmogenic right ventricular cardiomyopathy only in Gene2Phenotype (with definitive rating on the Cardiac panel), but associated with dilated cardiomyopathy in OMIM (MIM #612877).

Below are reported cases with biallelic variants and childhood-onset (onset before 18) cardiomyopathy:

PMID:31645976 (2019) reported two East Asian ARVC families, of which Family A's proband (III-2) was a 7-year-old boy who presented with heart-failure symptoms (abdominal distension, polypnea). He carried a compound heterozygous variants (p.Arg49His inherited from his mildly-affected 43-year-old father, plus p.Phe531Cys inherited from his unaffected mother).

PMID:33949662 (2021) reported the identification of a homozygous p.Arg119Ter variant in a patient with juvenile-onset severe biventricular heart failure, for which iPSC-cardiomyocyte modeling showed disrupted desmosome deposition and abnormal intercalated discs.

PMID:37288269 (2023) reported a single paediatric proband (8 years old) presented with arrhythmogenic cardiomyopathy initially misdiagnosed as myocarditis, driven by homozygous c.1592T>G (p.Phe531Cys), identified via whole-exome sequencing.

PMID:39706847 (2024) reported four unrelated Japanese patients with heterozygous p.Arg119Ter, of which one (Pt-1, a 19-year-old woman with ARVC) was compound heterozygous, carrying p.Arg119Ter together with p.Arg292Cys; her mother, a heterozygous p.Arg119Ter carrier alone, had an enlarged heart on chest X-ray but no formal ARVC diagnosis. This patient had symptom onset when she was 17 (congestion).

Created: 4 Sep 2026, 5:53 p.m. | Last Modified: 4 Sep 2026, 5:53 p.m.

Panel Version: 8.11

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Arrhythmogenic right ventricular dysplasia 10, OMIM:610193; arrhythmogenic right ventricular dysplasia 10, MONDO:0012434; Cardiomyopathy, dilated, 1BB, OMIM:612877; dilated cardiomyopathy 1BB, MONDO:0013030

Publications

• 31645976
• 33949662
• 37288269
• 39706847

Green List (high evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.

Created: 2 Dec 2019, 3:58 p.m. | Last Modified: 2 Dec 2019, 3:58 p.m.

Panel Version: 0.16

Green List (high evidence)

Arrhythmogenic right ventricular dysplasia 10, OMIM#610193; Cardiomyopathy, dilated, 1BB OMIM#612877

Created: 25 Mar 2019, 4:30 p.m.

PubMED: 29567486 - core gene. Lots of entries on HGMDPro for ARVC - including good evidence. Rasmussen Hum Mutat 00:19, 2013 presented a 12 family case series where two families had affected individuals of 17, 19 and 15 years of age with early onset ARVC.

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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