Paediatric or syndromic cardiomyopathy

Gene: SELENON

Red List (low evidence)

Comment on list classification: Biallelic SELENON variants cause an early-onset congenital muscular dystrophy characterised by spinal rigidity and respiratory failure, with no significant cardiomyopathy reported. Any observed cardiac abnormalities are secondary to respiratory failure in most of the reported cases. Hence, this gene should be rated red with the current evidence.

Created: 6 Sep 2025, 9:43 p.m. | Last Modified: 6 Sep 2025, 9:43 p.m.

Panel Version: 7.84

PMID:35868898 (2022) reviewed cases with cardiac involvement in SELENON-related myopathy, where cardiac abnormality was described in 15% of cases (29). The most frequently reported abnormality was pulmonary hypertension (16 patients), of whom eight patients were reported to have right ventricular (RV) dysfunction or increase of RV systolic pressure secondary to respiratory failure and three patients concomitant respiratory insufficiency, of whom two patients died of secondary cardiac failure within several years. Primary left ventricular (LV) dysfunction, including dilated cardiomyopathy (DCM) and decreased LV contractility, was only described in two patients. The first patient had a positive family history for idiopathic cardiomyopathy but not for SELENON-RM, and developed DCM at age of 42 years. No other cause of decreased LV contractility had been documented at paediatric age for the second patient.

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.Gly315Ser) in SELENON gene via analysis of data from singleton genome sequencing.

This gene has been associated with Congenital myopathy 3 with rigid spine in OMIM (MIM #602771, OMIM accessed on 06 September 2025) and with SELENON-related myopathy in Gene2Phenotype (with 'definitive' rating).
Sources: Literature

Created: 6 Sep 2025, 9:33 p.m. | Last Modified: 6 Sep 2025, 9:37 p.m.

Panel Version: 7.81

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital myopathy 3 with rigid spine, OMIM:602771; rigid spine muscular dystrophy 1, MONDO:0011271

Publications

• 35868898
• 39472908