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familial focal epilepsy with variable foci (FFEVF) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

familial focal epilepsy with variable foci

MONDO:0020310

Also known as:FFEVFepilepsy, familial focal, with variable focifamilial partial epilepsy with variable foci

Overview

Familial focal epilepsy with variable foci is a rare genetic epilepsy disorder characterized by autosomal dominant lesional and nonlesional focal epilepsy with variable penetrance. Focal seizures emanate from different cortical locations (temporal, frontal, centroparietal, parietal, parietaloccipital, occipital) in different family members, but for each individual a single focus remains constant throughout lifetime. Seizure type (tonic, tonic-clonic or hyperkinetic) and severity varies among family members and tends to decrease (but do not disappear) during adulthood. Many patients have an aura and show automatisms during diurnal seizures whereas others have nocturnal seizures. Most individuals are of normal intelligence but patients with intellectual disability, autistic spectrum disorder and obsessive-compulsive disorder have been described.

OnsetCHILDHOOD

ResearchLimited published research (9 articles)

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: childhood.

GeneReviews

Clinical Guidance

DEPDC5-related epilepsy encompasses a range of epilepsy syndromes, almost all of which are characterized by focal seizures, with seizure onset in a discrete area of the brain. While about 60% of individuals with DEPDC5-related epilepsy have a normal brain MRI , some have epilepsy associated with a cortical malformation, usually focal cortical dysplasia type II or hemimegalencephaly. Most affected individuals have a family history of focal epilepsy. To date, nearly 200 symptomatic individuals have been identified with a pathogenic variant in DEPDC5 [, , , , , , , , , , , , , , , , , , , , , , , , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. DEPDC5-Related Epilepsy: Frequency of Select Features in Symptomatic Individuals1

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 consensus clinical diagnostic criteria for DEPDC5-related epilepsy have been published to date.

Suggestive Findings

DEPDC5-related epilepsy should be suspected in individuals with the following clinical, neuroimaging, and EEG findings and family history.

Clinical findings

Source: GeneReviews — "DEPDC5-Related Epilepsy"

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 familial focal epilepsy with variable foci. The disease remains an area of unmet medical need.

Gene therapy approaches for familial focal epilepsy with variable foci have been reported in the published literature.

GeneReviews

Management Guidelines

No clinical practice guidelines for DEPDC5-related epilepsy have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with DEPDC5-related epilepsy, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with DEPDC5-Related Epilepsy

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.

Recommended Surveillance for Individuals with DEPDC5-Related Epilepsy

System/Concern | Evaluation | Frequency/Indication

Neurologic

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.

No clinical trials have been registered for familial focal epilepsy with variable foci.

9 publications have been identified in PubMed for familial focal epilepsy with variable foci. Research spans Case Report / Case Series (56%), Basic Science / Preclinical (22%), and Epidemiology / Natural History (11%).

Recent Publications

Wang S (2026). [PMID: 42210661](https://pubmed.ncbi.nlm.nih.gov/42210661/). *Mol Genet Genomic Med*. [Case Report / Case Series]
Wang PY (2026). [PMID: 41725720](https://pubmed.ncbi.nlm.nih.gov/41725720/). *Front Neurol*. [Basic Science / Preclinical]
Thormeyer V (2026). [PMID: 41260400](https://pubmed.ncbi.nlm.nih.gov/41260400/). *Neuropediatrics*. [Case Report / Case Series]
Langhammer F (2025). [PMID: 39849855](https://pubmed.ncbi.nlm.nih.gov/39849855/). *Hum Mol Genet*. [Basic Science / Preclinical]
Alsayed A (2025). [PMID: 40742146](https://pubmed.ncbi.nlm.nih.gov/40742146/). *Am J Med Genet A*. [Case Report / Case Series]

Data assembled from 4 of 12 sources · Last updated Sep 19, 2026, 9:41 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:98820

GARD

Genetic and Rare Diseases Info Center

GARD:13295

Questions for Your Care Team

→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

Feature	Feature Subtype (if applicable)	% of Persons w/Feature2	Comment
Epilepsy related complications	All types	100%3	Most commonly frontal lobe seizures/ sleep-related hypermotor epilepsy (30%)
Infantile spasms	6%	—	—
SUDEP	10%	—	—
Brain malformations	All types	20%	—
Focal cortical dysplasia	17%	Mostly type II	—
Hemimegalencephaly	2%	—	—
Polymicrogyria	1%	One person was reported w/bilateral polymicrogyria.4	—
Developmental/learning issues	Developmental delays (language, motor)	8%	—
Intellectual disability	12%	Most reported persons w/ID have FCD/focal epilepsy or drug-resistant epilepsy.	—
Developmental delay	7%	—	—
Autism spectrum disorder	5%	FCD = focal cortical dysplasia; SUDEP = sudden unexpected death in epilepsy Asymptomatic heterozygotes are common in families with DEPDC5-related epilepsy. Penetrance is therefore reduced and may be as low as 60% .	—

GeneReviews

Differential Diagnosis

The differential diagnosis for DEPDC5-related epilepsy includes other focal epilepsy syndromes as well as other genetic causes of (familial) focal epilepsy and focal cortical dysplasia . Of note, DEPDC5 is the most frequently involved gene among genetic focal epilepsies. Table 3. Genes of Interest in the Differential Diagnosis of DEPDC5-Related Epilepsy

Gene(s)	Disorder	MOI	Clinical Features of Disorder
CRH	CHRNA2-, CHRNA4, CHRNB2-, CRH-related ADSHE	AD	Frontal lobe seizures1
KCNT1-related epilepsy	AD	EIMFS ADSHE	Persons w/KCNT1-related ADSHE are more likely to develop seizures at a younger age, have cognitive comorbidity, display psychiatric behavioral issues than those w/ADSHE from other causes. LGI1
RELN	LGI1- RELN-related ADEAF3	AD	Focal epilepsy syndrome in which auditory symptoms /or receptive aphasia are prominent ictal manifestations. Affected persons have focal seizures ± altered consciousness; most typical features are auras consisting of humming or buzzing, or more complex auditory hallucinations.
NPRL2NPRL34	NPRL2- NPRL3-related focal epilepsy (OMIM 617116 617118)	AD	Familial focal epilepsies incl families w/ADSHE or FFEVF, of which some family members can have FCD type II5
MTOR	FCD (OMIM 607341) Smith-Kingsmore syndrome	AD orsomatic	Focal epilepsy, FCD type II, hemimegalencephaly, polymicrogyria
AKT3	FCD, hemimegalencephaly, AKT3-related megalencephaly-polydactyly-polymicrogyria-hydrocephalus syndrome6	AD orsomatic	Focal epilepsy, FCD type II, hemimegalencephaly, polymicrogyria

Source: GeneReviews — "DEPDC5-Related Epilepsy"

System/Concern	Evaluation	Comment
Neurologic	Assessment by neurologist for eval of suspected seizures, as indicated	To incl EEG high-resolution brain MRI to evaluate for focal cortical dysplasia or other brain malformations Assessment for predictive factors for SUDEP1
Development	Developmental assessment	To incl motor, adaptive, cognitive, speech-language eval; Eval for early intervention/ special education
Genetic counseling	By genetics professionals2	To obtain a pedigree inform affected persons their families re nature, MOI, implications of DEPDC5-related disorders to facilitate medical personal decision making Family support resources
Treatment of Manifestations in Individuals with DEPDC5-Related Epilepsy Manifestation/Concern	Treatment	Considerations/Other
Epilepsy	Standardized treatment w/ASM by experienced neurologist	Many ASMs may be effective; none has been demonstrated effective specifically for this disorder.; Education of parents/caregivers1
Brain malformations	Resective epilepsy surgery may be considered in persons w/focal epilepsy that is refractory to medical therapy.	In those w/FCD or hemimegalencephaly, epilepsy surgery should be explored early in disease course.; Surgical outcomes have been variable.2 Developmental delay/
Intellectual disability	Standard treatment, which may incl supportive developmental therapies (OT, PT, ST) to address specific delayed areas	Consultation w/neurodevelopmental specialist may be considered. Autism spectrum disorder
Family/Community	Ensure appropriate social work involvement to connect families w/local resources support.	ABA = applied behavior analysis; ASM = anti-seizure medication; FCD = focal cortical dysplasia; OT = occupational therapy; PT = physical therapy; ST = speech therapy Education of parents/caregivers regarding common seizure presentations is appropriate.
Recommended Surveillance for Individuals with DEPDC5-Related Epilepsy System/Concern	Evaluation	Frequency/Indication
Neurologic	Assess for new or ongoing manifestations, such as new-onset seizures /or changes in seizures or tone.	At each visit Repeat brain MRI (incl higher-resolution brain MRI).
Development	Monitor developmental progress.	At each visit

familial focal epilepsy with variable foci

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Neurologic

Research Landscape

Recent Publications

Medical References

External Resources

Orphanet

GARD

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Clinical Trials

Development

Family/Community