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progressive myoclonus epilepsy (PME) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

progressive myoclonus epilepsy

MONDO:0020074

Also known as:PMEepilepsy, progressive myoclonicprogressive myoclonic epilepsy

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Overview

A rare group of disorders characterized by the development of myoclonic and tonic-clonic epileptic seizures associated with progressive degeneration of the nervous system.

OnsetINFANTILE, CHILDHOOD, JUVENILE

Clinical Trials1 registered · 1 recruiting

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

Age of onset: infancy, childhood, adolescence.

GeneReviews

Clinical Guidance

KCNC1-related disorders encompass a spectrum of neurologic conditions distinguished by clinical features and pathogenic variant-specific molecular disease mechanisms. Affected individuals with loss-of-function pathogenic variants with a presumptive dominant-negative action may have myoclonic epilepsy and ataxia due to potassium (K+) channel mutation (MEAK; also known as progressive myoclonus epilepsy (PME) type 7/EPM7) or developmental and epileptic encephalopathy (DEE) (i.e., intractable epilepsy with developmental delay [DD]/intellectual disability [ID] associated with abnormal interictal EEG activity). Affected individuals with gain-of-function pathogenic variants may present with nonspecific DD/ID and gross motor impairment without myoclonus or epilepsy. To date, more than 60 individuals have been identified with a pathogenic variant in KCNC1 [, , , , , , , , , , , , , , , , , , , , , , , , , ]. The following description of the phenotypic features associated with this spectrum is based on these reports. Table 2. KCNC1-Related Disorders: Frequency of Select Features by Molecular Mechanism and Phenotype

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

KCNC1-related disorders encompass a spectrum of neurologic phenotypes that generally include one or more of the following features: developmental delay (DD)/ intellectual disability (ID), myoclonus (progressive or non-progressive), ataxia, and epilepsy. Within this spectrum, distinct phenotypes are identified, including myoclonus epilepsy and ataxia due to potassium (K+) channel mutation (MEAK; also known as progressive myoclonus epilepsy [PME] type 7/ EPM7) and developmental and epileptic encephalopathy (DEE). No consensus regarding clinical diagnostic criteria for this spectrum has been published.

Source: GeneReviews — "KCNC1-Related Disorders"

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for progressive myoclonus epilepsy. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for KCNC1-related disorders have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with a KCNC1-related disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 6.

KCNC1-Related Disorders: Recommended Surveillance

System/Concern | Evaluation | Frequency

Feeding/Growth

| • Measurement of growth parameters

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

1 clinical trial registered, 1 recruiting. Interventions under study include other interventions. Research is primarily sponsored by academic and government institutions.

99 publications have been identified in PubMed for progressive myoclonus epilepsy. Research spans Case Report / Case Series (35%), Basic Science / Preclinical (26%), and Gene Therapy / Novel Therapeutics (11%).

Research Type	Count	% of Total
Patient case studies	35	35%

Data assembled from 5 of 12 sources · Last updated Sep 17, 2026, 9:54 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:98261

GARD

Genetic and Rare Diseases Info Center

GARD:7140

Questions for Your Care Team

→Are any of the 1 active clinical trial a good fit for my situation?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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Molecular Mechanism	Phenotype	Feature	% of Persons w/Feature	Comment
Predicted loss-of-function pathogenic variants	Myoclonic epilepsy ataxia due to potassium (K+) channel mutation (MEAK)	Myoclonus	30/30 (100%)	Progressive, typically leading to impairment or loss of functional limb use nonambulation by 2nd to 3rd decade of life
Epilepsy	31/32 (97%)	Typically, generalized tonic-clonic seizures; less frequently, focal, tonic, /or absence seizures	—	—
Ataxia	29/30 (97%)	Progressive; may present as 1st observed symptom	—	—
Global DD/ID	3/30 (10%)	DD cognitive delay/ learning disabilities prior to seizure onset is not common. Mild learning disabilities can develop after seizure onset.	—	—
Cognitive decline	16/28 (57%)	Mild cognitive decline after seizure onset can be observed.	—	—
Developmental epileptic encephalopathy (DEE)	Epilepsy	8/8 (100%)	Epilepsy onset is in infancy is medication resistant; various seizure types can be observed.	—
Global DD/ID	7/7 (100%)	Infantile-onset DD/ID; ranges from moderate to severe impairment	—	—
Ataxia	6/8 (75%)	Non-progressive	—	—
Myoclonus	2/6 (33%) DD/ID without seizures1,2	Global DD/ID	8/8 (100%)	DD/ID ranges from mild to severe; ASD has been reported, while hypotonia has not.
Isolated non-progressive myoclonus	Myoclonus	1/1 (100%)	—	—
Predicted gain-of-function pathogenic variants	DD/ID hypotonia without epilepsy or myoclonus2	Global DD/ID	4/4 (100%)	DD/ID ranges from mild to severe; ASD has not been reported in affected persons.
Hypotonia	4/4 (100%)	Central hypotonia noted by age 1 yr. Based on , , , , , , , , , , , , , , , , , ASD = autism spectrum disorder; DD = developmental delay; ID = intellectual disability 1.	—	—

GeneReviews

Differential Diagnosis

Myoclonus epilepsy and ataxia due to potassium (K+) channel mutation (MEAK). See . Table 3. Genes of Interest in the Differential Diagnosis of Myoclonus Epilepsy and Ataxia due to Potassium Channel Mutation

Gene(s)	Disorder	MOI	Clinical Features of Disorder
DRPLA	AD	Myoclonus, epilepsy, ataxia	Choreoathetosis, dementia Multiple genes incl:CLN3PPT1TPP
Neuronal ceroid lipofuscinoses	AR(AD)1	Seizures, epilepsy	Progressive loss of vision; early-onset progressive cognitive motor decline
CSTB	Progressive myoclonic epilepsy type 1 (EPM1; Unverricht-Lundborg disease)	AR	Nearly identical
CTSA	Galactosialidosis (OMIM 256540)	AR	Myoclonus ataxia may be present.
Progressive myoclonus epilepsy, Lafora type	AR	Progressive myoclonic epilepsy, generalized tonic-clonic seizures, absence seizures	Focal occipital seizures presenting as transient blindness or visual hallucinations; neurodegeneration w/in 1st 2 decades of life resulting dementia
GBA1	Gaucher disease type 3	AR	Childhood-onset myoclonus ± ataxia or seizures
GOSR2	Progressive myoclonic epilepsy 6 (OMIM 614018)	AR	Nearly identical
KCTD7	Progressive myoclonic epilepsy 3 ± intracellular inclusions (KCTD7-related progressive myoclonic epilepsy; see also Neuronal Ceroid Lipofuscinoses Overview)	AR	Early-onset progressive myoclonic epilepsy following initial normal development
MERRF	MT	Myoclonic epilepsy, ataxia	Muscle weakness, myopathy, sensorineural hearing loss
POLG	POLG-related ataxia neuropathy spectrum (See POLG-Related Disorders.)	AR	Ataxia, seizures, myoclonus2
PRICKLE1	PRICKLE1-related progressive myoclonic epilepsy w/ataxia (EPM1B) (See PRICKLE1-Related Disorders.)	AR	Early-onset progressive myoclonic epilepsy; additional seizure types incl generalized tonic-clonic; ataxia often progressive
SCARB2-related action myoclonus – renal failure syndrome	AR	Progressive myoclonic epilepsy	Kidney failure in some persons; action-induced or...

Source: GeneReviews — "KCNC1-Related Disorders"

Kisho

progressive myoclonus epilepsy

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Feeding/Growth

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Neurologic

Myoclonus

Ataxia

Development

Feeding

Therapies Under Investigation

Clinical Trials

Neurologic

Development

Musculoskeletal

Psychiatric

Family/Community

Transition to adult care

Recent Publications

progressive myoclonus epilepsy

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Feeding/Growth

Research Landscape

Medical References

External Resources

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Neurologic

Myoclonus

Ataxia

Development

Feeding

Therapies Under Investigation

Clinical Trials

Neurologic

Development

Musculoskeletal

Psychiatric

Family/Community

Transition to adult care

Recent Publications