Paediatric or syndromic cardiomyopathy

Gene: TANGO2

Green List (high evidence)

Comment on list classification: Although cardiomyopathy was reported only in a very small proportion of patients with biallelic TANGO2 variants from earlier studies, 19 patients (70%) from the multi-centre study from PMID:35568137 and both unrelated patients from PMID:4015630 were reported with cardiomyopathy.

As there are over 20 patients reported with cardiomyopathy, this gene can be promoted to green rating on this panel in the next GMS update.

Created: 5 Sep 2025, 1:22 p.m. | Last Modified: 5 Sep 2025, 1:22 p.m.

Panel Version: 7.73

Comment on phenotypes: This gene has been associated with relevant phenotypes in both OMIM (MIM #616878, accessed on 05 September 2025) and Gene2Phenotype (TANGO2-related infancy-onset recurrent metabolic crises with encephalocardiomyopathy with 'definitive' rating on the DD panel).

Created: 5 Sep 2025, 1:12 p.m. | Last Modified: 5 Sep 2025, 1:12 p.m.

Panel Version: 7.72

PMID:26805781 (2016) reported the identification of biallelic variants (a missense variant and two different intragenic deletions) in 12 patients from nine unrelated families with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to life-threatening cardiac tachyarrhythmias. Hypertrophic cardiomyopathy was reported in a patient from a family with three affected patients (with homozygous exons 3-9 deletion).

PMID:30245509 (2018) reported the identification of biallelic TANGO2 variants (five different variants including the previously described exon 3-9 intragenic deletion in either homozygous or compound heterozygous states) in 14 individuals from 11 unrelated families with a complex clinical phenotype including primarily neurological presentations. Dilated cardiomyopathy was reported in two patients from a family (compound heterozygous for p.Arg32Ter & p.Arg26Lys variants) and left ventricular hypertrophy was reported in one of three patients from family 1 (with 3C>G and exons-3-9 deletion).

PMID:31339582 (2020) reported nine patients from seven unrelated families with biallelic TANGO2 variants (exons 3-9 deletion and small variants). One unrelated patient (subject 5) that harboured a hemizygous deletion of exons 3-9 (second variant was not identified) was reported with hypertrophic cardiomyopathy.

PMID:32527145 (2020) reported a 6-year-old female patient atypical cardiomyopathy, who was identified to harbour a hemizygous deletion of exons 3-9 in the TANGO2 gene via next-generation sequencing.

PMID:35568137 (2022) conducted a retrospective multicentre chart review of TANGO2 deficiency disorder patients admitted with cardiac crises, where 27 children were admitted for 43 cardiac crises at 14 centres. These patients were reported with either homozygous or compound heterozygous variants including small variants and intragenic deletions in TANGO2 gene. Arrhythmias included ventricular tachycardia in 21 (78%), supraventricular tachycardia in 3 (11%), and heart block in 1 (4%). Nineteen patients (70%) developed cardiomyopathy, and 20 (74%) experienced a cardiac arrest.

PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort, of which one adult patient with unspecified cardiomyopathy was identified with an intragenic homozygous deletion in TANGO2 gene via analysis of data from trio genome sequencing.

PMID:40156300 (2025) reported two unrelated patients with biallelic TANGO2 pathogenic variants (homozygous deletion of exons 4-6 in one and c.605+1G>A in the other). Both patients developed ventricular tachyarrhythmias, and the echocardiogram showed cardiomyopathy.
Sources: Literature

Created: 5 Sep 2025, 12:58 p.m. | Last Modified: 5 Sep 2025, 1:36 p.m.

Panel Version: 7.73

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, OMIM:616878; recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome, MONDO:0018820

Publications

• 26805781
• 30245509
• 31339582
• 32527145
• 35568137
• 39472908
• 40156300