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developmental and epileptic encephalopathy, 14 - Clinical Profile, Genes & Research | Kisho | Kisho

Features include always present findings: Low muscle tone (hypotonia), Brain atrophy, Generalized-onset motor seizure, and Interictal epileptiform activity and others; and common findings: Delayed CNS myelination, Cerebral cortical atrophy, Generalized hypotonia, and Thin corpus callosum and others. 31 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	22	Clonus, Focal clonic seizure, Cerebral cortical atrophy
Muscles	5	Cerebral cortical atrophy, Low muscle tone (hypotonia), Generalized hypotonia
Heart and blood vessels	1	Focal autonomic seizure with palpitations/tachycardia/bradycardia/asystole
Head and neck	1	Microcephaly

GeneReviews

Clinical Guidance

KCNT1-related epilepsy encompasses a range of epilepsy syndromes. The most common phenotypes reported in individuals with KCNT1-related epilepsy are epilepsy of infancy with migrating focal seizures (EIMFS) and autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).

Epilepsy Phenotype

EIMFS is an early-infantile epileptic encephalopathy characterized by seizures beginning in the first six months of life with associated developmental plateau or regression. The seizures are primarily focal motor, variably with secondary generalization, but also include tonic, clonic, tonic-clonic, myoclonic, and epileptic spasms . Autonomic manifestations (e.g., perioral cyanosis, flushing, apnea) are common. Seizures progress to become nearly continuous by age six to nine months.

Source: GeneReviews — "KCNT1-Related Epilepsy"

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

No formal diagnostic criteria for KCNT1-related epilepsy have been published to date. KCNT1-related epilepsy is most often associated with two phenotypes: epilepsy of infancy with migrating focal seizures (EIMFS) and autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Less often, KCNT1 pathogenic variants are associated with epilepsy with variable presentation.

Suggestive Findings

KCNT1-related epilepsy of infancy with migrating focal seizures (EIMFS) should be suspected in individuals with the following history and findings:

Source: GeneReviews — "KCNT1-Related Epilepsy"

GeneReviews

Differential Diagnosis

Phenotypic and EEG features associated with KCNT1 pathogenic variants are not sufficient to diagnose KCNT1-related epilepsy. All genes known to be associated with early-infantile epileptic encephalopathy (30 have been identified; see OMIM Phenotypic Series) should be included in the differential diagnosis of KCNT1-related epilepsy including other genes less commonly associated with epilepsy of infancy with migrating focal seizures (SCN1A, SCN2A, SLC12A5, SLC25A22, TBC1D24, PLCB1) and autosomal dominant nocturnal frontal lobe epilepsy (CHRNA4, CHRNB2, DEPDC5, CRH). Note: At seizure onset, it is most important to distinguish KCNT1-related epilepsy from potentially treatable causes of early infantile-onset epileptic encephalopathy, such as neurometabolic disorders, CNS infection, structural brain lesions, and other syndromes . Table 2. Treatable Disorders Associated with Early Infantile-Onset Epileptic Encephalopathy

Conditions	Gene(s)	MOI	Clinical Findings	Treatment

Genetic testing for KCNT1 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for developmental and epileptic encephalopathy, 14 has been reported in the published literature.

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 developmental and epileptic encephalopathy, 14. An additional 2 compounds hold orphan drug designation.

Orphan Drug Designations

While no drugs are FDA-approved specifically for developmental and epileptic encephalopathy, 14, some of the following designated compounds may be used off-label in clinical practice. Treatment decisions should be made in consultation with a specialist familiar with this condition.

The following drugs have received orphan drug designation from the FDA for developmental and epileptic encephalopathy, 14. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Brand Name	Generic Name	Sponsor	Designated	Exclusivity End	Designation Status
antrafenine	antrafenine	UniSA Ventures Pty Ltd	2024	—	Designated
Anti-epileptic small molecule inhibitor of KCNT1	Anti-epileptic small molecule inhibitor of KCNT1	Actio Biosciences	2024	—	Designated

Gene therapy approaches for developmental and epileptic encephalopathy, 14 have been reported in the published literature.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with KCNT1-related epilepsy, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:

Prolonged video EEG monitoring to evaluate electroclinical and electrographic seizure burden in consultation with a pediatric epileptologist
Evaluation by a movement disorder specialist if dictated by clinical presentation
Consideration of echocardiogram to evaluate for pulmonary collaterals
Electrocardiogram (EKG) to evaluate for cardiac rhythm abnormalities
Cognitive and behavioral assessment
Physical, occupational, and speech therapy evaluation
Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Seizures. KCNT1-related epilepsy is often refractory to conventional anticonvulsants.

Source: GeneReviews — "KCNT1-Related Epilepsy"

Clinical Trials

2 trials found

Explore Trials

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.

2 clinical trials registered, 2 recruiting. Interventions under study include drug therapy. Pipeline includes 1 PHASE2, 1 PHASE1. Research is primarily industry-sponsored.

207 publications have been identified in PubMed for developmental and epileptic encephalopathy, 14. Kisho has analyzed 83 by research type. Research spans Epidemiology / Natural History (31%), Review / Meta-Analysis (29%), and Basic Science / Preclinical (12%).

Research Type	Count	% of Total
Disease patterns and progression	26	31%
Research summaries	24	29%
Laboratory research	10	12%
Clinical study results	9	11%
Patient case studies	7	8%
Testing and diagnosis research	4	5%
Other research	2	2%
New treatment approaches	1	1%

Recent Publications

Dlugos DJ (2026). [PMID: 41133912](https://pubmed.ncbi.nlm.nih.gov/41133912/). *Epilepsia*. [Clinical Trial Publication]
Ludwig NN (2026). [PMID: 41533235](https://pubmed.ncbi.nlm.nih.gov/41533235/). *Qual Life Res*. [Epidemiology / Natural History]
Krygier M (2026). [PMID: 42200219](https://pubmed.ncbi.nlm.nih.gov/42200219/). *Ann Clin Transl Neurol*. [Epidemiology / Natural History]
Cheng L (2026). [PMID: 42220997](https://pubmed.ncbi.nlm.nih.gov/42220997/). *Front Pediatr*. [Review / Meta-Analysis]
Marchionni E (2026). [PMID: 41615502](https://pubmed.ncbi.nlm.nih.gov/41615502/). *Neurogenetics*. [Case Report / Case Series]
AlHadi NE (2026). [PMID: 42048301](https://pubmed.ncbi.nlm.nih.gov/42048301/). *Am J Case Rep*. [Case Report / Case Series]
Zhang G (2026). [PMID: 41133935](https://pubmed.ncbi.nlm.nih.gov/41133935/). *Epilepsia*. [Basic Science / Preclinical]
Mondragon E (2026). [PMID: 41215607](https://pubmed.ncbi.nlm.nih.gov/41215607/). *Epilepsia*. [Clinical Trial Publication]
GBD 2023 Mental Disorder Collaborators (2026). [PMID: 42167272](https://pubmed.ncbi.nlm.nih.gov/42167272/). *Lancet*. [Review / Meta-Analysis]
Boeri S (2026). [PMID: 41724124](https://pubmed.ncbi.nlm.nih.gov/41724124/). *Epilepsy Behav*. [Case Report / Case Series]

Kisho

developmental and epileptic encephalopathy, 14

Overview

Clinical Presentation

Clinical Guidance

Epilepsy Phenotype

Explore clinical features

Genetic Landscape

Penetrance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Orphan Drug Designations

Management Guidelines

Evaluations Following Initial Diagnosis

Treatment of Manifestations

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Patient Support

Patient Advocacy Groups

Medical References

External Resources

OMIM

GARD

Questions for Your Care Team

Questions for Your Care Team

Latest News & Developments

Phenotypic and transcriptomic characterization of biallelic RNU2-2 developmental and epileptic encephalopathy.

A de novo NR2F1 c.330 C > A variant in Bosch-Boonstra-Schaaf optic atrophy syndrome presenting with early-onset developmental and epileptic encephalopathy.

Optical genome mapping identifies previously undetected causal variants in early-onset developmental epileptic encephalopathies.

developmental and epileptic encephalopathy, 14

Overview

Clinical Presentation

Clinical Guidance

Epilepsy Phenotype

Explore clinical features

Genetic Landscape

Penetrance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Orphan Drug Designations

Management Guidelines

Evaluations Following Initial Diagnosis

Treatment of Manifestations

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Patient Support

Patient Advocacy Groups

Medical References

External Resources

OMIM

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Latest News & Developments

Phenotypic and transcriptomic characterization of biallelic RNU2-2 developmental and epileptic encephalopathy.

A de novo NR2F1 c.330 C > A variant in Bosch-Boonstra-Schaaf optic atrophy syndrome presenting with early-onset developmental and epileptic encephalopathy.

Optical genome mapping identifies previously undetected causal variants in early-onset developmental epileptic encephalopathies.