| PME subtype/syndrome | Causal gene(s) | Typical onset | Core features | Mechanism/pathology theme | Established/approved disease-specific therapy (if any) | Key citations (PMID/DOI) |
|---|---|---|---|---|---|---|
| Unverricht-Lundborg disease / EPM1 | **CSTB** (usually biallelic promoter dodecamer repeat expansion; other pathogenic variants also reported) | Late childhood to early adolescence, typically ~6–15 years | Stimulus- and action-sensitive myoclonus, generalized seizures, photosensitivity, ataxia, dysarthria; myoclonus often remains highly disabling even when seizures improve (pqac-00000011, pqac-00000012, pqac-00000016) | Reduced cystatin B expression causes impaired protease regulation, GABAergic/interneuron dysfunction, oxidative stress/mitochondrial abnormalities, lysosomal involvement, and early microglial/astroglial neuroinflammation (pqac-00000012, pqac-00000014, pqac-00000018) | **No approved disease-specific therapy**; symptomatic ASMs used. Preclinical **AAV9 CSTB gene replacement** improved neuroinflammation, neurodegeneration, and ataxia in mice (pqac-00000013, pqac-00000014) | DOI: 10.3390/genes15020171; DOI: 10.3390/cells13020170; DOI: 10.21203/rs.3.rs-3112340/v1 |
| Lafora disease / EPM2 | **EPM2A (laforin)**, **NHLRC1/EPM2B (malin)** | Usually adolescence; mean onset reported ~13.4 years in large cohort (pqac-00000026) | Progressive myoclonus and generalized seizures, ataxia/cerebellar signs, cognitive decline/dementia, progressive loss of autonomy; often fatal within ~5–15 years, median survival ~11 years (pqac-00000019, pqac-00000021, pqac-00000026) | Defective glycogen metabolism with formation of **polyglucosan Lafora bodies**; associated autophagy impairment, ER stress/UPR, oxidative stress, and neuroinflammation (pqac-00000020, pqac-00000024, pqac-00000025) | **No approved disease-specific therapy**. Repurposed **metformin** has orphan designation and showed slower progression in observational human data plus benefit in models; experimental strategies include **GYS1 antisense**, antibody-enzyme fusion (**VAL-0417**), trehalose, 4-PBA, gene therapy concepts (pqac-00000020, pqac-00000021, pqac-00000022, pqac-00000024) | DOI: 10.3390/genes15020171; DOI: 10.1007/s13311-022-01304-w; DOI: 10.1186/s12883-025-04253-x |
| Neuronal ceroid lipofuscinoses (PME-associated forms; e.g., CLN2, CLN6, CLN14/KCTD7-related) | Multiple **CLN genes**; examples: **TPP1/CLN2**, **CLN6**, **KCTD7/CLN14**, **MFSD8/CLN7**, **PPT1/CLN1**, **CTSD/CLN10**, **CTSF/CLN13** (pqac-00000027, pqac-00000029, pqac-00000030) | Variable by subtype; often infancy/childhood; examples include CLN2 ~4–8 years, CLN6 ~18 months–8 years (pqac-00000027, pqac-00000028) | Seizures/myoclonus, developmental regression, ataxia, progressive cognitive and motor decline, **vision loss**, brain atrophy; cortical hyperexcitability with enlarged SSEPs/PPR in some forms (pqac-00000027, pqac-00000028, pqac-00000029) | Lysosomal storage neurodegeneration with accumulation of autofluorescent ceroid/lipofuscin material, impaired lysosomal function and autophagy, neuronal loss, brain and retinal degeneration, glial activation (pqac-00000027, pqac-00000029) | **Yes for CLN2:** **cerliponase alfa** enzyme replacement is approved; active development of additional enzyme and viral gene therapies for other NCLs (pqac-00000027, pqac-00000030, pqac-00000034) | DOI: 10.3390/genes15020171; DOI: 10.3389/fncel.2024.1445003; NCT01907087 |
| Sialidosis type 1 | **NEU1** | Usually later childhood to adolescence/young adulthood | PME phenotype with myoclonus and generalized tonic-clonic seizures; visual/retinal findings can aid diagnosis (pqac-00000004, pqac-00000007) | Lysosomal neuraminidase deficiency; storage disease biology with multisystem/ocular clues (pqac-00000004, pqac-00000007) | **No approved disease-specific therapy for PME manifestation**; case reports suggest **perampanel** may improve myoclonus and GTCs (pqac-00000004) | DOI: 10.3390/genes15020171; DOI: 10.3389/fneur.2024.1455467 |
| MERRF (myoclonic epilepsy with ragged-red fibers) | Typically mitochondrial **MT-TK** and other mtDNA variants | Childhood to adolescence, but variable | Myoclonus, epilepsy, ataxia, myopathy/exercise intolerance, multisystem mitochondrial features (pqac-00000002) | Mitochondrial translation/oxidative phosphorylation defect with energy failure and neurodegeneration (pqac-00000002) | **No approved disease-specific therapy**; mainly supportive and mitochondrial disease management (pqac-00000002) | DOI: 10.3390/genes15020171 |
| North Sea progressive myoclonus epilepsy | **GOSR2** | Early childhood ataxia followed by myoclonic seizures in mid-childhood (pqac-00000004) | Early ataxia/areflexia, progressive myoclonic seizures, skeletal features, severe disability; premature death reported (pqac-00000004) | Vesicular trafficking defect; neurodevelopmental/neurodegenerative PME phenotype (pqac-00000004) | **No approved disease-specific therapy**; modified Atkins diet showed modest benefit in small open-label study (from broader literature summarized in context) (pqac-00000004) | DOI: 10.3390/genes15020171 |
| SMA-PME | **ASAH1** | Childhood, variable | Progressive muscle weakness/atrophy with myoclonic and generalized seizures; neurological deterioration (pqac-00000002) | Acid ceramidase deficiency with ceramide accumulation; lysosomal storage disease spectrum overlapping Farber disease (pqac-00000002) | **No approved disease-specific therapy**; symptomatic/supportive care, experimental enzyme/gene therapy concepts in broader ASAH1 field (pqac-00000002) | DOI: 10.3390/genes15020171 |


*Table: This table summarizes major progressive myoclonus epilepsy syndromes, their exemplar causal genes, characteristic onset and features, mechanistic themes, and whether any disease-specific therapy is established. It is useful as a compact cross-disease reference for diagnosis, knowledge-base curation, and treatment landscape review.*