| Phenotype / clinical feature | HPO term suggestion | Frequency among affected individuals | Age of onset | Severity | Progression pattern | Anatomical systems / structures affected |
|---|---|---|---|---|---|---|
| Ptosis | HP:0000508 | Core feature; 7/7 in OPDM_NOTCH2NLC series; generally characteristic across OPDM subtypes (pqac-00000001, pqac-00000011, pqac-00000000, pqac-00000006, pqac-00000014) | Usually adult-onset; can range from infancy/juvenile to late adulthood in NOTCH2NLC-associated cases (1–68 years overall in one series) (pqac-00000011) | Variable | Progressive, insidious (pqac-00000000, pqac-00000014) | Eyelids; extraocular musculature; cranial muscles |
| External ophthalmoplegia / ophthalmoparesis | HP:0000602 | Core feature; 7/7 in OPDM_NOTCH2NLC series; repeatedly described as typical of OPDM (pqac-00000001, pqac-00000011, pqac-00000000, pqac-00000003, pqac-00000014) | Usually adult-onset; occasionally juvenile/early onset in OPDM3 (pqac-00000011) | Variable | Progressive (pqac-00000000, pqac-00000014) | Extraocular muscles; ocular motor system |
| Dysphagia | HP:0002015 | Common core bulbar feature; present in 5/7 OPDM_NOTCH2NLC cases in one table and broadly typical across OPDM (pqac-00000011, pqac-00000000, pqac-00000014) | Adult-onset in most; may appear later than limb or ocular symptoms (pqac-00000011, pqac-00000014) | Variable to severe | Progressive (pqac-00000000, pqac-00000014) | Pharyngeal muscles; swallowing apparatus |
| Dysarthria | HP:0001260 | 7/7 in OPDM_NOTCH2NLC series; frequently reported in bulbar involvement (pqac-00000001, pqac-00000011) | Adult-onset in most; broad range across subtypes (pqac-00000011) | Variable | Progressive (pqac-00000001) | Bulbar musculature; speech system |
| Facial muscle weakness | HP:0000297 | Common core feature; 5/7 in OPDM_NOTCH2NLC series; repeatedly described in OPDM overviews (pqac-00000000, pqac-00000011, pqac-00000014) | Usually adult-onset (pqac-00000011, pqac-00000014) | Variable | Progressive (pqac-00000000) | Facial musculature; cranial muscles |
| Masseter weakness | HP:0030319 | Characteristic but frequency not well quantified; included in classic disease descriptions (pqac-00000000) | Adult-onset | Variable | Progressive | Masticatory muscles; craniofacial musculature |
| Distal limb muscle weakness | HP:0002460 | Defining feature; all 7 OPDM_NOTCH2NLC patients had limb weakness, commonly distal-predominant; also emphasized in major OPDM definitions (pqac-00000001, pqac-00000011, pqac-00000000, pqac-00000003, pqac-00000014) | Usually adult-onset; occasionally juvenile/childhood onset in OPDM3 (pqac-00000011) | Moderate to severe; variable | Slowly progressive (pqac-00000000, pqac-00000014) | Distal upper/lower limb skeletal muscles |
| Proximal limb weakness (variable, less typical) | HP:0003701 | Less typical than distal weakness; some OPDM3 cases had D=P or proximal upper limb involvement; review notes weakness can be proximal/asymmetrical in some subtypes (pqac-00000011, pqac-00000014) | Adult-onset usually | Variable | Progressive | Proximal limb muscles; shoulder/hip girdle |
| Diffuse limb weakness / generalized myopathy | HP:0003323 | Seen in some patients/subtypes; broad myopathic presentation described in reviews and some series (pqac-00000014, pqac-00000011) | Adult-onset usually | Variable | Progressive | Appendicular skeletal muscle system |
| Muscle atrophy | HP:0003202 | Present in some OPDM_NOTCH2NLC cases (distal or diffuse atrophy in table); frequent in advanced disease (pqac-00000011) | Develops after weakness onset | Variable | Progressive | Limb skeletal muscles |
| Neck weakness | HP:0000467 | Present in a subset of OPDM_NOTCH2NLC cases (3/7 noted in one table) (pqac-00000011) | Variable | Mild to moderate | Progressive | Cervical skeletal muscles |
| Rimmed vacuoles on muscle biopsy | HP:0012115 | Hallmark pathology across OPDM; present in diagnostic descriptions and all major subtype studies (pqac-00000000, pqac-00000001, pqac-00000006, pqac-00000014) | Detected at biopsy after symptomatic onset | Variable pathologic burden | Progressive histopathologic correlate | Skeletal muscle fibers |
| Intranuclear inclusions in muscle fibers | HP:0034335 | Seen in OPDM, especially subtype-associated p62/ubiquitin/SUMO-positive inclusions; non-muscle INIs support OPDM over OPMD (pqac-00000001, pqac-00000006, pqac-00000014) | After disease onset; biopsy finding | Variable | Progressive pathologic correlate | Myonuclei; also blood vessels, peripheral nerve bundles, muscle spindle-associated cells in OPDM |
| Myopathic EMG / chronic myopathic change | HP:0003458 | Common in classic OPDM descriptions; frequency not uniformly quantified in retrieved texts (pqac-00000000, pqac-00000014) | After symptom onset | Variable | Progressive | Skeletal muscle electrical function |
| Small angular fibers / internal nuclei / fibrosis on biopsy | HP:0200037 | Common pathological findings, though not always quantified; noted in OPDM muscle pathology (pqac-00000005, pqac-00000011) | After symptom onset | Variable | Progressive histologic change | Skeletal muscle tissue |
| Peripheral neuropathy | HP:0009830 | Variable extra-muscular feature; confirmed by nerve conduction in 3/7 OPDM_NOTCH2NLC cases; review highlights overlap with NIID and peripheral neuropathy (pqac-00000011, pqac-00000014, pqac-00000008) | Often adult-onset, may accompany or follow myopathy | Variable | Progressive | Peripheral nerves; motor and sometimes sensory nerves |
| Sensory disturbance | HP:0003474 | 3/7 in OPDM_NOTCH2NLC table (pqac-00000011) | Adult-onset usually | Variable | Progressive | Peripheral sensory nervous system |
| Tremor | HP:0001337 | Reported in some OPDM_NOTCH2NLC patients and in broader FNOP-spectrum overlap (pqac-00000011, pqac-00000014) | Usually later adult onset | Mild to moderate | Progressive or fluctuating | Cerebellar / extrapyramidal motor systems |
| Cerebellar ataxia | HP:0001251 | Reported in a subset of OPDM_NOTCH2NLC patients and broader NOTCH2NLC-related spectrum (pqac-00000011, pqac-00000014) | Adult-onset usually | Variable | Progressive | Cerebellum; gait and coordination systems |
| Leukoencephalopathy / white matter disease | HP:0002352 | Present in some OPDM_NOTCH2NLC cases (3/7 in one table had leukoencephalopathy) and central-spectrum overlap disorders (pqac-00000011, pqac-00000014) | Usually adult-onset | Variable | Progressive | Cerebral white matter |
| Cognitive impairment / dementia features | HP:0100543 | Not a core OPDM feature, but lower HDS-R scores and CNS overlap reported in some NOTCH2NLC-related cases; broader spectrum includes cognitive decline (pqac-00000011, pqac-00000014) | Later adult onset usually | Variable | Progressive | Cerebral cortex / cognition networks |
| Developmental delay (rare) | HP:0001263 | Rare; 1 patient in OPDM_NOTCH2NLC series had onset at age 1 year with developmental delay (pqac-00000011) | Infancy / childhood in rare cases | Variable | Static plus superimposed progressive disease possible | Neurodevelopmental systems |
| Visual disturbance / retinopathy / retinal pigmentary degeneration | HP:0000505 | Reported in several OPDM_NOTCH2NLC patients; review notes retinopathy in NOTCH2NLC-related disorders (pqac-00000011, pqac-00000014) | Variable, often adult-onset | Variable | Progressive | Retina; visual system |
| Hearing impairment | HP:0000365 | Reported in several OPDM_NOTCH2NLC patients; earlier literature cited overlap with sensorineural hearing loss (pqac-00000011, pqac-00000001) | Adult-onset usually | Variable | Progressive | Auditory system |
| Cataract / photophobia / miosis (variable ocular non-motility features) | HP:0000518 / HP:0000613 / HP:0000616 | Individual cases reported in OPDM_NOTCH2NLC table (pqac-00000011) | Variable | Mild to moderate | Variable / progressive | Lens, iris, visual system |
| Deep tendon reflex reduction | HP:0001315 | Reduced reflexes documented in all 7 OPDM_NOTCH2NLC patients (degrees varied) (pqac-00000011) | After neuromuscular involvement develops | Mild to moderate | Progressive | Peripheral nerve / neuromuscular reflex arcs |
| Elevated serum creatine kinase | HP:0003236 | Variable; CK values ranged from 63 to 1886 IU/L in 7 OPDM_NOTCH2NLC patients (pqac-00000011) | After muscle involvement begins | Mild to moderate elevation; variable | Variable over disease course | Skeletal muscle injury biomarker |
| Asymmetric muscle involvement on imaging | HP:0009837 | Reported in at least one OPDM_NOTCH2NLC patient by muscle CT; review also notes asymmetry can occur (pqac-00000011, pqac-00000014) | Established disease | Variable | Progressive | Limb and pelvic skeletal muscles |
| Cardiac conduction / ECG abnormalities (uncommon) | HP:0011707 | Rare but reported in OPDM_NOTCH2NLC: long QT in 1 case, AV block/LVH in 1 case (pqac-00000011) | Adult-onset | Variable | Progressive or stable | Cardiac conduction system / myocardium |
| Respiratory involvement | HP:0002093 | Not well characterized in retrieved OPDM papers; no strong evidence for a common core feature (pqac-00000014) | Not established | Unknown / variable | Unknown | Respiratory muscles / pulmonary system |


*Table: This table summarizes core and variable clinical manifestations reported for oculopharyngodistal myopathy, including suggested HPO terms, approximate frequencies where available, onset patterns, severity, progression, and affected systems. It is useful for phenotype curation and knowledge-base annotation across genetically heterogeneous OPDM subtypes.*