| Clinical entity / trigger | Principal gene(s) and inheritance | Typical attack / onset features | Mechanism | Practical treatment |
|---|---|---|---|---|
| **PKD**; sudden voluntary movement or startle | **PRRT2** (usually AD, incomplete penetrance ~74.5%–77.6%; recurrent **c.649dupC** common, up to ~80% of PRRT2 mutation carriers), **TMEM151A** (AD, lower penetrance ~53.8%) | Brief recurrent dystonia/choreoathetosis; attacks usually **<1 min**; onset typically childhood/early adolescence; male:female about **2–4:1**; PKD prevalence estimated **~1:150,000**. PRRT2-PKD tends to have earlier onset, longer duration, choreoathetosis, bilateral involvement; TMEM151A cases tend to be purer dystonia with shorter attacks and more sporadic presentation. | PRRT2 loss-of-function/haploinsufficiency disrupts presynaptic signaling and neuronal excitability: altered **Nav1.2/Nav1.6** regulation, impaired **Na+/K+ ATPase** activity, and abnormal synaptic vesicle docking/SNARE-associated release; PKD is viewed as both **channelopathy and synaptopathy**. TMEM151A data support loss-of-function/haploinsufficiency, but protein function remains less defined. Cerebellar and basal ganglia-thalamo-cortical circuits are implicated. | **Carbamazepine** or **oxcarbazepine** are first-line; often highly effective, especially in PRRT2-related PKD, sometimes at low dose. TMEM151A-linked disease also improves, though complete remission may be less consistent. Trigger avoidance (sleep deprivation, stress, stimulants if relevant); genetic counseling. (pqac-00000008, pqac-00000009, pqac-00000010, pqac-00000011, pqac-00000012, pqac-00000026) |
| **PNKD**; no clear kinesigenic trigger, commonly stress/alcohol/caffeine/strong emotion | **PNKD** (AD, near-complete penetrance ~95%; recurrent **p.Ala7Val** and **p.Ala9Val**), **KCNMA1** (AD; PNKD3) | PNKD attacks are longer than PKD, typically **10 min to 1 h**, but may last up to **12 h**; onset from childhood to early adolescence (mean about **5 years**, range **6 months–35 years**); attacks may be infrequent, only a few per year. KCNMA1-associated disease may include paroxysmal dyskinesia with or without epilepsy and “drop-attack”/immobility-like episodes. | **PNKD** protein is synaptic and linked to regulation of neurotransmitter release/cellular redox-stress pathways. In mouse PNKD models, dyskinesia is associated with **striatal indirect pathway (iMSN) hypoactivity** and aberrant **endocannabinoid-mediated suppression** of glutamatergic input. **KCNMA1** variants alter **BK potassium channel** function: GOF alleles (e.g., **N999S**, **D434G**) increase neuronal firing and lower seizure threshold; cortical pyramidal and cerebellar Purkinje cell hyperexcitability are implicated. | Avoid/limit **alcohol, caffeine, emotional stress** where relevant. Classic PNKD often responds poorly to medication but may improve with age. For KCNMA1-related disease, case-guided symptomatic therapy may include **dextroamphetamine** for immobility/drop-attack phenotype; mechanistic studies suggest **BK inhibition** as a future precision approach, but this is not established clinical standard. (pqac-00000006, pqac-00000015, pqac-00000020, pqac-00000024, pqac-00000025) |
| **PED**; prolonged exercise/fatigue, sometimes fasting | **SLC2A1** (usually AD; rare AR reported), metabolic mimics including **ECHS1** (AR), **PDHA1/PDHX/DLAT** (X-linked/AR pyruvate dehydrogenase complex disorders), **BCKD complex** genes (AR), **GLDC** (AR) | Often leg-predominant chorea/dystonia after exertion; may coexist with epilepsy. In SLC2A1-related PED, median CSF:blood glucose ratio reported **0.52** (normal **>0.60**); GLUT1 phenotype spectrum includes PED, PKD/PNKD, epilepsy/absence epilepsy, intellectual/developmental issues, and spasticity. | **SLC2A1/GLUT1** deficiency reduces glucose transport across the **blood-brain barrier**, causing brain energy failure; imaging implicated **corticostriate glucose metabolism** abnormalities in PED. Metabolic mimics reflect impaired mitochondrial/pyruvate or amino acid metabolism. | **Ketogenic diet** is the key disease-modifying therapy for SLC2A1-related PED; early diagnosis matters. In the original SLC2A1 PED/epilepsy series, **3 patients** were successfully treated with ketogenic diet. Consider targeted metabolic therapy in mimics (e.g., **thiamine** in pyruvate dehydrogenase deficiency; dietary manipulation in MSUD-related disease) and avoidance of provoking exertion/fasting. (pqac-00000015, pqac-00000016, pqac-00000019) |
| **Pleiotropic paroxysmal dyskinesias**; mixed triggers including sleep, exertion, stress, spontaneous episodes | **ADCY5** (AD), **GNAO1** (AD), **SCN8A** (AD) | Often broader neurodevelopmental/epileptic phenotypes rather than isolated dyskinesia. ADCY5 can cause **PKD, PED, PNKD, nocturnal paroxysmal movements**, facial/orofacial dyskinesia, hypotonia, developmental delay. GNAO1 commonly presents with severe hyperkinetic episodes plus developmental and epileptic encephalopathy. SCN8A may cause infantile seizures with later PKD/PKD-like episodes. | **ADCY5** affects striatal **cAMP signaling**; **GNAO1** perturbs G-protein signaling with network hyperkinetic instability; **SCN8A** alters **Nav1.6** sodium channel excitability. These genes exemplify the overlap between movement-disorder, epilepsy, and developmental phenotypes. | **ADCY5:** caffeine may reduce symptoms; **clonazepam**, **acetazolamide**, and selected severe cases **DBS** are used in practice. **GNAO1:** severe hyperkinetic crises may lead to consideration of **DBS**. **SCN8A:** **carbamazepine/oxcarbazepine** may help when sodium-channel hyperexcitability is suspected. Broad NGS-based diagnosis is especially useful because treatment is genotype-informed rather than purely phenomenologic. (pqac-00000001, pqac-00000007, pqac-00000015, pqac-00000017) |


*Table: This table summarizes the major inherited paroxysmal dyskinesia entities by trigger pattern, principal genes, mechanism, and practical treatment implications. It is designed as a compact genotype-guided reference for differentiating classic PKD/PNKD/PED from pleiotropic dyskinesia syndromes.*