Paediatric or syndromic cardiomyopathy

Gene: ADSSL1

Green List (high evidence)

Comment on list classification: Hypertrophic cardiomyopathy has been reported in a significant proportion of patients with biallelic ADSSL1 variants - 12 patients (25%) in PMID:32646962 and two additional unrelated families. Hence, this gene can be promoted to green rating on this panel in the next GMS update.

Created: 6 Sep 2025, 6:38 p.m. | Last Modified: 6 Sep 2025, 6:38 p.m.

Panel Version: 7.80

The 'new-gene-name' tag has been added as the official HGNC gene symbol of ADSSL1 is ADSS1.

Created: 6 Sep 2025, 6:34 p.m. | Last Modified: 6 Sep 2025, 6:34 p.m.

Panel Version: 7.79

Comment on phenotypes: OMIM phenotype accessed on 06 September 2025.

Created: 6 Sep 2025, 6:32 p.m. | Last Modified: 6 Sep 2025, 6:32 p.m.

Panel Version: 7.79

PMID:32646962 (2020) reported the identification of 63 patients from 59 families with biallelic variants of ADSSL1. Seven distinct variants were identified in total, of which c.781G>A and c.919delA accounted for 53.2% and 40.5% of alleles, respectively, suggesting the presence of common founders, while the other five were novel. Most of the reported patients presented with variable myopathy with distal and proximal limb muscle weakness (often childhood onset of exercise intolerance) and facial and bulbar involvement were common in them. Left ventricular hypertrophy (LVH) was noted in 12 (25.0%) of 48 patients on EKG or echocardiography. ADSSL1 variants in nine of these patients were identified by WES and 3 were identified by Sanger sequencing. Patient 12 developed progressive heart failure with LVH before the onset of apparent muscle weakness at age 20, and he died due to multiple organ failure at age 25.

PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort, of which one adult male patient with unspecified cardiomyopathy was identified with a homozygous missense variant (p.Asp261Asn) in ADSSL1 gene via analysis of data from trio genome sequencing.

PMID:40302423 (2025) reported the identification of compound heterozygous pathogenic variants (c.781G>A/c.919delA) in ADSSL1 gene in two siblings with ADSSL1-myopathy. LVH was observed in both siblings and pathologically confirmed in the case where autopsy was done.
Sources: Literature

Created: 6 Sep 2025, 6:31 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myopathy, distal, 5, OMIM:617030; myopathy, distal, 5, MONDO:0014877; hypertrophic cardiomyopathy, MONDO:0005045

Publications

• 32646962
• 39472908
• 40302423