To analyze the clinical and genetic features of oculopharyngodistal myopathy (OPDM) patients and compare the phenotypic differences among various causative genes.

A total of 65 genetically confirmed OPDM patients from 43 unrelated families, who were admitted to the Department of Neurology, Peking University First Hospital between January 2008 and December 2025, were retrospectively included.The general demographic data, clinical manifestations, laboratory/auxiliary examinations, muscle pathology, and genetic test results were systematically collected and analyzed. The clinical and pathological characteristics among different OPDM subtypes were compared.

Among the 65 patients(39 male and 26 female), the mean age of onset was (31.20±10.43) years (range: 14 to 63 years). The initial symptom was predominantly distal limb weakness (67.44%), which gradually progressed to involve the extraocular muscles, pharyngeal muscles, facial muscles and proximal limb muscles. Serum creatine kinase levels were mildly to moderately elevated. Muscle pathological examinations revealed rimmed vacuoles and intranuclear inclusions (within muscle fibers). The mean duration from onset to diagnosis was (12.33±7.88) years (range: 1 to 32 years). All probands had negative results on conventional next-generation whole-exome sequencing; pathogenic variants were identified through third-generation long-read sequencing or OPDM-targeted repeat-primed polymerase chain reaction(RP-PCR). Among the 43 families, OPDM2 subtype was the most common genetic subtype (n=25), followed by OPDM4 subtype (n=8), OPDM3 subtype (n=6), OPDM1 subtype (n=3), and OPDM5 subtype (n=1). All OPDM probands subtypes were highly similar in age at onset and muscle pathological changes. However, OPDM3 subtype may be complicated by cerebral white matter lesions and other extra-muscular organ involvement. The proportion of OPDM4 patients who developed distal limb weakness only after 10 years of disease onset(40.0%) was significantly higher than that of other subtypes (all 0.0%, P=0.0122).

OPDM2 was the predominant subtype in this study. All subtypes share similar age of onset and muscular pathological changes, yet exhibit distinct disease progression patterns. Future multicenter prospective cohort studies are warranted to further elucidate the clinical characteristics, pathogenetic mechanisms, and prognostic differences among OPDM subtypes.