Objective To summarize the clinical characteristics and genetic mutation spectrum of patients with SELENON-related myopathy(SELENON-RM), in order to improve awareness among physicians.

Methods A total of 12 patients from independent families with genetically confirmed SELENON-RM at Peking Union Medical College Hospital between January 2016 and December 2025 were retrospectively included. Clinical data were collected, and their clinical and genetic features were analyzed.

Results The mean age at presentation was(16.7±9.7) years(range: 6-35 years), with males accounting for 66.7%(8/12). Patients presented with delayed motor development since early childhood, followed by a relatively stable disease course without significant progression over several years. Among 10 patients tested for serum creatine kinase, 4 had normal levels and 6 showed elevated levels. Electromyography performed in 9 patients indicated myogenic damage in both upper and lower limbs. Muscle biopsy in 6 patients revealed myopathic changes, including variation in muscle fiber size and fiber-type disproportion with predominance of type Ⅰ fibers. Pulmonary function tests in 5 patients demonstrated restrictive ventilatory defects. Overnight polysomnography in 6 patients revealed severe nocturnal hypoxemia. Genetic analysis showed that among the 12 patients, 9 patients had compound heterozygous mutations in the SELENON gene, 1 patient had a homozygous mutation(with each allele inherited from one parent), and 2 patients had a pathogenic mutation identified in only one allele. 13 distinct mutation sites were detected, of which 12 had been previously reported in the ClinVar database, while 1 was novel.

Conclusions Patients with SELENON-RM usually develop symptoms in early life, presenting with motor developmental delay, scoliosis or rigid spine, and frequently with occult but significant respiratory involvement. Patients in this study appear to predominantly carry compound heterozygous variants, and exons 1 and 11 of the SELENON gene may represent important mutational hotspots. The diagnosis of SELENON-RM can be challenging. Appropriate genetic testing should be selected based on characteristic clinical features, and early respiratory monitoring and supportive interventions, including non-invasive ventilation, should be strengthened to improve patient outcomes.