| Subtype designation | Gene name | Gene location (chromosome) | Repeat type | Normal repeat range | Pathogenic repeat range | Year of discovery | Key clinical distinguishing features |
|---|---|---|---|---|---|---|---|
| OPDM1 | **LRP12** | 8q24.3 | 5′UTR **CGG/GGC** repeat expansion | ~13–45 repeats | ~85–289 repeats; most reported patients ~125–150 | 2019 | Classic OPDM phenotype with ptosis, ophthalmoplegia, dysphagia/dysarthria, facial and distal limb weakness; usually adult onset; rimmed vacuoles and intranuclear/cytoplasmic filamentous inclusions on biopsy; predominantly myopathic presentation, though shorter/intermediate expansions have been linked to motor neuropathy/ALS-spectrum phenotypes in later work (pqac-00000007, pqac-00000013, pqac-00000014, pqac-00000008) |
| OPDM2 | **GIPC1** | 19p13.3 | 5′UTR **GGC/CGG** repeat expansion | Not clearly established in retrieved texts | Expanded alleles reported in affected patients; disease generally associated with large expansions, exact validated pathogenic threshold not stated in retrieved contexts | 2020 | Clinically similar to OPDM1 with progressive ptosis, external ophthalmoplegia, bulbar involvement, and distal-predominant weakness; RNA-seq implicated p53 signaling, ubiquitin-mediated proteolysis, and ribosome pathways; recent work supports translation into toxic polyglycine protein (uGIPpolyG) (pqac-00000000, pqac-00000010, pqac-00000018) |
| OPDM3 | **NOTCH2NLC** | 1q21.2 | 5′UTR **CGG/GGC** repeat expansion | Not clearly established in retrieved texts | Often **>100 repeats** in reported OPDM cases; examples included 116, 128, 132, 135, 139, 184, 217, and 674-repeat expanded alleles | 2020 | OPDM with frequent additional neurologic features: peripheral neuropathy, leukoencephalopathy, cerebellar ataxia/tremor, retinal disease, hearing impairment, and occasional cognitive involvement; all seven Japanese cases had ptosis, ophthalmoplegia, dysarthria, and weakness; overlaps with NIID/FNOP spectrum (pqac-00000001, pqac-00000011, pqac-00000014) |
| OPDM4 | **RILPL1** | 12q24.31 | Noncoding **CCG/CGG-related** repeat expansion | Not clearly established in retrieved texts | Pathogenic expansion reported, but exact range not provided in retrieved contexts | 2022 | Similar core OPDM phenotype; review notes many patients present initially with ptosis or dysphagia; pathology includes p62-positive inclusions and rimmed vacuoles; recent mechanistic work shows antisense RILPL1-derived polyglycine protein (asRILpolyG) with relatively nuclear localization and muscle/CNS toxicity in models (pqac-00000006, pqac-00000014, pqac-00000016, pqac-00000017) |
| OPML / OPDM-related LOC642361 subtype | **LOC642361 / NUTM2B-AS1** | 10q22.3 | Noncoding **CGG/GGC** repeat expansion | Not clearly established in retrieved texts | Pathogenic expansion reported, exact range not provided in retrieved contexts | 2024 | Typically described as **oculopharyngeal myopathy with leukoencephalopathy (OPML)** rather than pure OPDM; combines oculopharyngeal/distal myopathic features with white-matter disease and broader neurologic involvement; recent studies show translation into LOC6polyG found in p62-positive inclusions (pqac-00000004, pqac-00000009, pqac-00000016) |
| OPDM5 | **ABCD3** | 1p21.3 | Noncoding **CGG/GGC** repeat expansion | Not clearly established in retrieved texts | Pathogenic expansion reported, exact range not provided in retrieved contexts | 2024 | Core OPDM phenotype reported; generally grouped with isolated OPDM rather than OPML in review literature; mechanistically thought to share the common CGG-repeat disease biology of toxic polyglycine production/RNA toxicity, but subtype-specific distinguishing clinical data were limited in retrieved contexts (pqac-00000007, pqac-00000013) |
| OPDM (overall, genetically heterogeneous) | Multiple genes: **LRP12, GIPC1, NOTCH2NLC, RILPL1, LOC642361/NUTM2B-AS1, ABCD3** | Multiple chromosomes | Predominantly noncoding **CGG/GGC** (and for RILPL1, reported **CCG/CGG-related**) repeat expansions | Gene-specific and incompletely standardized | Gene-specific; larger repeats generally correlate with earlier onset in GIPC1 and NOTCH2NLC, while methylation modifies phenotype especially in LRP12 | 2019–2024 | Shared syndrome: slowly progressive adult-onset ptosis, ophthalmoplegia, bulbar weakness, facial weakness, and distal limb weakness with rimmed vacuoles; shared mechanisms include toxic polyglycine proteins, p62-positive inclusions, and possible RNA toxicity; age at onset and multisystem involvement vary by gene and methylation state (pqac-00000005, pqac-00000013, pqac-00000014, pqac-00000009) |


*Table: This table summarizes the currently recognized genetic subtypes linked to oculopharyngodistal myopathy and related OPML, including genes, repeat classes, reported size ranges, and major clinical distinctions. It is useful for comparing the expanding repeat-expansion spectrum and highlighting where evidence remains incomplete in the retrieved literature.*