FFEVF1
MCID: EPL196
MIFTS: 41

Epilepsy, Familial Focal, with Variable Foci 1 (FFEVF1)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Epilepsy, Familial Focal, with Variable Foci 1

MalaCards integrated aliases for Epilepsy, Familial Focal, with Variable Foci 1:

Name: Epilepsy, Familial Focal, with Variable Foci 1 57 74 29 6
Ffevf 57 53 25 59 74
Familial Focal Epilepsy with Variable Foci 53 25 59 37
Familial Partial Epilepsy with Variable Foci 53 25 59
Epilepsy, Partial, with Variable Foci 57 13 72
Epilepsy, Familial Focal, with Variable Foci 57 40
Partial Epilepsy with Variable Foci 25 74
Ffevf1 57 74
Fpevf 57 74
Epilepsy, Familial Focal, with Variable Foci; Ffevf 57
Epilepsy, Partial, with Variable Foci; Fpevf 57

Characteristics:

Orphanet epidemiological data:

59
familial focal epilepsy with variable foci
Inheritance: Autosomal dominant;

OMIM:

57
Miscellaneous:
incomplete penetrance
phenotypic variability
onset usually in first or second decades
variable age at onset (range infancy to adulthood)

Inheritance:
autosomal dominant


HPO:

32
epilepsy, familial focal, with variable foci 1:
Inheritance autosomal dominant inheritance
Onset and clinical course incomplete penetrance


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

KEGG 37 H02214
MeSH 44 D004828
Orphanet 59 ORPHA98820
UMLS 72 C1858477

Summaries for Epilepsy, Familial Focal, with Variable Foci 1

Genetics Home Reference : 25 Familial focal epilepsy with variable foci (FFEVF) is an uncommon form of recurrent seizures (epilepsy) that runs in families. Seizures associated with FFEVF can begin at any time from infancy to adulthood. The seizures are described as focal or partial, which means they begin in one region of the brain and do not cause a loss of consciousness. In more than 70 percent of affected individuals, these seizures begin in one of two areas of the brain, either the temporal lobe or the frontal lobe. The region of the brain where the seizures start tends to stay the same over time. In rare instances, seizure activity that starts in one area spreads to affect the entire brain and causes a loss of consciousness, muscle stiffening, and rhythmic jerking. Episodes that begin as partial seizures and spread throughout the brain are known as secondarily generalized seizures. Among family members with FFEVF, individuals may not have the same brain region affected (variable foci), meaning that one person's seizures may not begin in the same part of the brain as their affected relative. Some individuals with FFEVF also have a brain malformation called focal cortical dysplasia. Seizures in these individuals are typically not well-controlled with medication. Most people with FFEVF are intellectually normal, and there are no problems with their brain function between seizures. However, some people with FFEVF have developed psychiatric disorders (such as schizophrenia), behavioral problems, or intellectual disability. It is unclear whether these additional features are directly related to epilepsy in these individuals.

MalaCards based summary : Epilepsy, Familial Focal, with Variable Foci 1, also known as ffevf, is related to focal epilepsy and epilepsy. An important gene associated with Epilepsy, Familial Focal, with Variable Foci 1 is DEPDC5 (DEP Domain Containing 5), and among its related pathways/superpathways are mTOR signaling pathway and mTOR signaling pathway (KEGG). Affiliated tissues include brain, temporal lobe and occipital lobe, and related phenotypes are intellectual disability and autistic behavior

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 98820DefinitionFamilial 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.Visit the Orphanet disease page for more resources.

OMIM : 57 Familial focal epilepsy with variable foci (FFEVF) is an autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions in different family members. Many patients have an aura and show automatisms during the seizures, whereas others may have nocturnal seizures. There is often secondary generalization. Some patients show abnormal interictal EEG, and some patients have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. Penetrance of the disorder is incomplete (summary by Klein et al., 2012). Detailed electrophysiologic, brain imaging, and/or histologic studies have indicated that some patients have subtle or clear evidence of focal cortical dysplasia (FCD) (Baulac et al., 2015). (604364)

KEGG : 37
Familial focal epilepsy with variable foci (FFEVF) is an autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Recently, it has been identified that mutations in the mTOR pathway regulators, DEPDC5, NPRL2 and NPRL3 cause this disease.

UniProtKB/Swiss-Prot : 74 Epilepsy, familial focal, with variable foci 1: An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions in different family members. Many patients have an aura and show automatisms during the seizures, whereas others may have nocturnal seizures. There is often secondary generalization. Some patients show abnormal interictal EEG, and some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. Penetrance of the disorder is incomplete.

Related Diseases for Epilepsy, Familial Focal, with Variable Foci 1

Graphical network of the top 20 diseases related to Epilepsy, Familial Focal, with Variable Foci 1:



Diseases related to Epilepsy, Familial Focal, with Variable Foci 1

Symptoms & Phenotypes for Epilepsy, Familial Focal, with Variable Foci 1

Human phenotypes related to Epilepsy, Familial Focal, with Variable Foci 1:

32 (show all 6)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 32 occasional (7.5%) HP:0001249
2 autistic behavior 32 occasional (7.5%) HP:0000729
3 nocturnal seizures 32 occasional (7.5%) HP:0031951
4 focal cortical dysplasia type i 32 very rare (1%) HP:0032047
5 focal cortical dysplasia type iia 32 very rare (1%) HP:0032052
6 hemimegalencephaly 32 HP:0007206

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
intellectual disability (in some patients)
temporal lobe epilepsy
seizure, focal or multifocal onset
parietal lobe epilepsy
frontal lobe epilepsy
more
Neurologic Behavioral Psychiatric Manifestations:
autism spectrum disorder (in some patients)

Clinical features from OMIM:

604364

Drugs & Therapeutics for Epilepsy, Familial Focal, with Variable Foci 1

Search Clinical Trials , NIH Clinical Center for Epilepsy, Familial Focal, with Variable Foci 1

Genetic Tests for Epilepsy, Familial Focal, with Variable Foci 1

Genetic tests related to Epilepsy, Familial Focal, with Variable Foci 1:

# Genetic test Affiliating Genes
1 Epilepsy, Familial Focal, with Variable Foci 1 29 DEPDC5

Anatomical Context for Epilepsy, Familial Focal, with Variable Foci 1

MalaCards organs/tissues related to Epilepsy, Familial Focal, with Variable Foci 1:

41
Brain, Temporal Lobe, Occipital Lobe, Parietal Lobe

Publications for Epilepsy, Familial Focal, with Variable Foci 1

Articles related to Epilepsy, Familial Focal, with Variable Foci 1:

(show all 24)
# Title Authors PMID Year
1
A recurrent mutation in DEPDC5 predisposes to focal epilepsies in the French-Canadian population. 38 8 71
24283814 2014
2
Mutations in DEPDC5 cause familial focal epilepsy with variable foci. 38 8 71
23542697 2013
3
Familial focal epilepsy with variable foci mapped to chromosome 22q12: expansion of the phenotypic spectrum. 38 8 71
22780917 2012
4
Familial focal epilepsy with focal cortical dysplasia due to DEPDC5 mutations. 8 71
25623524 2015
5
DEPDC5 mutations in families presenting as autosomal dominant nocturnal frontal lobe epilepsy. 8 71
24814846 2014
6
Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. 8 71
24585383 2014
7
Mutations of DEPDC5 cause autosomal dominant focal epilepsies. 8 71
23542701 2013
8
Familial partial epilepsy with variable foci: clinical features and linkage to chromosome 22q12. 8 71
15329069 2004
9
Familial partial epilepsy with variable foci in a Dutch family: clinical characteristics and confirmation of linkage to chromosome 22q. 8 71
14510823 2003
10
Dominant partial epilepsies. A clinical, electrophysiological and genetic study of 19 European families. 8 71
10825362 2000
11
Mapping of a gene determining familial partial epilepsy with variable foci to chromosome 22q11-q12. 8 71
10577924 1999
12
Familial partial epilepsy with variable foci: a new partial epilepsy syndrome with suggestion of linkage to chromosome 2. 8 71
9851433 1998
13
DEPDC5-Related Epilepsy 38 71
27683934 2016
14
Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia. 8
27173016 2016
15
Mutations in the mammalian target of rapamycin pathway regulators NPRL2 and NPRL3 cause focal epilepsy. 8
26505888 2016
16
DEPDC5 mutations in genetic focal epilepsies of childhood. 8
24591017 2014
17
The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. 8
21219302 2011
18
Autosomal dominant nocturnal frontal-lobe epilepsy: genetic heterogeneity and evidence for a second locus at 15q24. 8
9758605 1998
19
Genetic linkage studies in familial frontal epilepsy: exclusion of the human chromosome regions homologous to the El-1 mouse locus. 8
8991790 1995
20
Autosomal dominant nocturnal frontal lobe epilepsy. A distinctive clinical disorder. 8
7895015 1995
21
Magnetoencephalogram-assisted diagnosis of familial focal epilepsy with variable foci in a Chinese family with a novel DEPDC5 mutation. 38
31225799 2019
22
Inclusion of hemimegalencephaly into the phenotypic spectrum of NPRL3 pathogenic variants in familial focal epilepsy with variable foci. 38
31111464 2019
23
DEPDC5 mutations are not a frequent cause of familial temporal lobe epilepsy. 38
26216793 2015
24
Genetics advances in autosomal dominant focal epilepsies: focus on DEPDC5. 38
25194487 2014

Variations for Epilepsy, Familial Focal, with Variable Foci 1

ClinVar genetic disease variations for Epilepsy, Familial Focal, with Variable Foci 1:

6 (show top 50) (show all 353)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 DEPDC5 NM_001242897.2(DEPDC5): c.434G> A (p.Trp145Ter) single nucleotide variant Pathogenic rs1060501488 22:32174105-32174105 22:31778119-31778119
2 DEPDC5 NM_001242897.2(DEPDC5): c.1845del (p.Arg615fs) deletion Pathogenic rs1060501487 22:32215186-32215186 22:31819200-31819200
3 DEPDC5 NC_000022.10: g.(?_32150888)_(32150985_?)del deletion Pathogenic 22:32150888-32150985 22:31754902-31754999
4 DEPDC5 NC_000022.10: g.(?_32154512)_(32174174_?)del deletion Pathogenic 22:32154512-32174174 :0-0
5 DEPDC5 NM_001242897.2(DEPDC5): c.2660_2685del (p.His887fs) deletion Pathogenic rs1555900914 22:32241096-32241121 22:31845110-31845135
6 DEPDC5 NM_001242897.2(DEPDC5): c.1385_1386del (p.Ala461_Tyr462insTer) deletion Pathogenic rs1555882921 22:32206567-32206568 22:31810581-31810582
7 DEPDC5 NC_000022.10: g.(?_32205577)_(32211218_?)del deletion Pathogenic 22:32205577-32211218 22:31809591-31815232
8 DEPDC5 NM_001242897.2(DEPDC5): c.346C> T (p.Arg116Ter) single nucleotide variant Pathogenic rs1315483224 22:32162637-32162637 22:31766651-31766651
9 DEPDC5 NC_000022.10: g.(?_32150888)_(32211218_?)del deletion Pathogenic 22:32150888-32211218 22:31754902-31815232
10 DEPDC5 NM_001242897.2(DEPDC5): c.865C> T (p.Gln289Ter) single nucleotide variant Pathogenic rs759952667 22:32193683-32193683 22:31797697-31797697
11 DEPDC5 NM_001242897.2(DEPDC5): c.21C> G (p.Tyr7Ter) single nucleotide variant Pathogenic rs768241563 22:32150928-32150928 22:31754942-31754942
12 DEPDC5 NM_001242897.2(DEPDC5): c.1663C> T (p.Arg555Ter) single nucleotide variant Pathogenic rs587776973 22:32211195-32211195 22:31815209-31815209
13 DEPDC5 NM_001242897.2(DEPDC5): c.489_491del (p.Phe164del) deletion Pathogenic rs587776974 22:32179898-32179900 22:31783912-31783914
14 DEPDC5 NM_001242897.2(DEPDC5): c.3807G> A (p.Trp1269Ter) single nucleotide variant Pathogenic rs587776975 22:32289641-32289641 22:31893655-31893655
15 DEPDC5 NM_001242897.2(DEPDC5): c.1122del (p.Leu374fs) deletion Pathogenic rs879255234 22:32200188-32200188 22:31804202-31804202
16 DEPDC5 NM_001242897.2(DEPDC5): c.715C> T (p.Arg239Ter) single nucleotide variant Pathogenic rs587776976 22:32188751-32188751 22:31792765-31792765
17 DEPDC5 NM_001242897.2(DEPDC5): c.982C> T (p.Arg328Ter) single nucleotide variant Pathogenic rs587776977 22:32198725-32198725 22:31802739-31802739
18 DEPDC5 NM_001242897.2(DEPDC5): c.3025C> T (p.Arg1009Ter) single nucleotide variant Pathogenic rs587777458 22:32253534-32253534 22:31857548-31857548
19 DEPDC5 NM_001242897.2(DEPDC5): c.1459C> T (p.Arg487Ter) single nucleotide variant Pathogenic rs587777459 22:32210991-32210991 22:31815005-31815005
20 DEPDC5 NM_001242897.2(DEPDC5): c.2293C> T (p.Arg765Ter) single nucleotide variant Pathogenic rs541024038 22:32239092-32239092 22:31843106-31843106
21 DEPDC5 NM_001242897.2(DEPDC5): c.2121-2A> G single nucleotide variant Pathogenic rs797044545 22:32234669-32234669 22:31838683-31838683
22 DEPDC5 NM_001242897.2(DEPDC5): c.4267C> T (p.Gln1423Ter) single nucleotide variant Pathogenic rs797044546 22:32302238-32302238 22:31906252-31906252
23 DEPDC5 NM_001242897.2(DEPDC5): c.418C> T (p.Gln140Ter) single nucleotide variant Pathogenic rs786205703 22:32174089-32174089 22:31778103-31778103
24 DEPDC5 NM_001242897.2(DEPDC5): c.279+1G> A single nucleotide variant Pathogenic rs886039246 22:32161047-32161047 22:31765061-31765061
25 DEPDC5 NM_001242897.2(DEPDC5): c.435G> A (p.Trp145Ter) single nucleotide variant Pathogenic rs886039247 22:32174106-32174106 22:31778120-31778120
26 DEPDC5 NM_001242897.2(DEPDC5): c.454_455del (p.Met152fs) deletion Pathogenic rs886039248 22:32174125-32174126 22:31778139-31778140
27 DEPDC5 NM_001242897.2(DEPDC5): c.484-1G> A single nucleotide variant Pathogenic rs886039249 22:32179892-32179892 22:31783906-31783906
28 DEPDC5 NM_001242897.2(DEPDC5): c.492_496del (p.Arg165fs) deletion Pathogenic rs886039250 22:32179901-32179905 22:31783915-31783919
29 DEPDC5 NM_001242897.2(DEPDC5): c.526C> T (p.Gln176Ter) single nucleotide variant Pathogenic rs886039251 22:32179935-32179935 22:31783949-31783949
30 DEPDC5 NM_001242897.2(DEPDC5): c.624+1G> A single nucleotide variant Pathogenic rs886039252 22:32180862-32180862 22:31784876-31784876
31 DEPDC5 NM_001242897.2(DEPDC5): c.59-1G> C single nucleotide variant Pathogenic rs886039243 22:32154531-32154531 22:31758545-31758545
32 DEPDC5 NM_001242897.2(DEPDC5): c.132dup (p.Asn45fs) duplication Pathogenic rs886039244 22:32154605-32154605 22:31758619-31758619
33 DEPDC5 NM_001242897.2(DEPDC5): c.193+1G> A single nucleotide variant Pathogenic rs886039245 22:32156689-32156689 22:31760703-31760703
34 DEPDC5 NM_001242897.2(DEPDC5): c.727C> T (p.Arg243Ter) single nucleotide variant Pathogenic rs772872014 22:32188763-32188763 22:31792777-31792777
35 DEPDC5 NM_001242897.2(DEPDC5): c.730C> T (p.Gln244Ter) single nucleotide variant Pathogenic rs886039253 22:32188766-32188766 22:31792780-31792780
36 DEPDC5 NM_001242897.2(DEPDC5): c.783_786del (p.Asn261fs) deletion Pathogenic rs886039254 22:32193601-32193604 22:31797615-31797618
37 DEPDC5 NM_001242897.2(DEPDC5): c.856C> T (p.Arg286Ter) single nucleotide variant Pathogenic rs886039255 22:32193674-32193674 22:31797688-31797688
38 DEPDC5 NM_001242897.2(DEPDC5): c.918C> G (p.Tyr306Ter) single nucleotide variant Pathogenic rs886039256 22:32194614-32194614 22:31798628-31798628
39 DEPDC5 NM_001242897.2(DEPDC5): c.985del (p.Thr329fs) deletion Pathogenic rs886039257 22:32198728-32198728 22:31802742-31802742
40 DEPDC5 NM_001242897.2(DEPDC5): c.1093_1099dup (p.Val367fs) duplication Pathogenic rs886039258 22:32200159-32200165 22:31804173-31804179
41 DEPDC5 NM_001242897.2(DEPDC5): c.1114C> T (p.Gln372Ter) single nucleotide variant Pathogenic rs886039259 22:32200180-32200180 22:31804194-31804194
42 DEPDC5 NM_001242897.2(DEPDC5): c.1264C> T (p.Arg422Ter) single nucleotide variant Pathogenic rs757511744 22:32202154-32202154 22:31806168-31806168
43 DEPDC5 NM_001242897.2(DEPDC5): c.1393C> T (p.Gln465Ter) single nucleotide variant Pathogenic rs886039260 22:32206575-32206575 22:31810589-31810589
44 DEPDC5 NM_001242897.2(DEPDC5): c.1555C> T (p.Gln519Ter) single nucleotide variant Pathogenic rs886039261 22:32211087-32211087 22:31815101-31815101
45 DEPDC5 NM_001242897.2(DEPDC5): c.1750_1756del (p.Leu584fs) deletion Pathogenic rs886039262 22:32215087-32215093 22:31819101-31819107
46 DEPDC5 NM_001242897.2(DEPDC5): c.1759C> T (p.Arg587Ter) single nucleotide variant Pathogenic rs886039263 22:32215100-32215100 22:31819114-31819114
47 DEPDC5 NM_001242897.2(DEPDC5): c.2156del (p.Gln719fs) deletion Pathogenic rs886039264 22:32234706-32234706 22:31838720-31838720
48 DEPDC5 NM_001242897.2(DEPDC5): c.2386C> T (p.Arg796Ter) single nucleotide variant Pathogenic rs578185749 22:32239185-32239185 22:31843199-31843199
49 DEPDC5 NM_001242897.2(DEPDC5): c.2812C> T (p.Gln938Ter) single nucleotide variant Pathogenic rs886039265 22:32242844-32242844 22:31846858-31846858
50 DEPDC5 NM_001242897.2(DEPDC5): c.3694C> T (p.Arg1232Ter) single nucleotide variant Pathogenic rs886039269 22:32275699-32275699 22:31879713-31879713

UniProtKB/Swiss-Prot genetic disease variations for Epilepsy, Familial Focal, with Variable Foci 1:

74
# Symbol AA change Variation ID SNP ID
1 DEPDC5 p.Ala452Val VAR_069263 rs202226316
2 DEPDC5 p.Arg485Gln VAR_069264 rs886039278
3 DEPDC5 p.Ser1073Arg VAR_069265 rs754608531
4 DEPDC5 p.Ser1104Leu VAR_069266 rs79027628
5 DEPDC5 p.Val90Ile VAR_072363 rs768456731
6 DEPDC5 p.Val272Leu VAR_072364 rs187334123
7 DEPDC5 p.Thr864Met VAR_072365 rs564667614
8 DEPDC5 p.Ser1162Gly VAR_072366 rs886039280

Expression for Epilepsy, Familial Focal, with Variable Foci 1

Search GEO for disease gene expression data for Epilepsy, Familial Focal, with Variable Foci 1.

Pathways for Epilepsy, Familial Focal, with Variable Foci 1

Pathways related to Epilepsy, Familial Focal, with Variable Foci 1 according to KEGG:

37
# Name Kegg Source Accession
1 mTOR signaling pathway hsa04150

Pathways related to Epilepsy, Familial Focal, with Variable Foci 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.26 NPRL3 NPRL2 DEPDC5

GO Terms for Epilepsy, Familial Focal, with Variable Foci 1

Cellular components related to Epilepsy, Familial Focal, with Variable Foci 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosome GO:0005764 9.33 NPRL3 NPRL2 DEPDC5
2 lysosomal membrane GO:0005765 9.13 NPRL3 NPRL2 DEPDC5
3 GATOR1 complex GO:1990130 8.8 NPRL3 NPRL2 DEPDC5

Biological processes related to Epilepsy, Familial Focal, with Variable Foci 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of GTPase activity GO:0043547 9.43 NPRL3 NPRL2 DEPDC5
2 regulation of autophagosome assembly GO:2000785 9.16 NPRL3 NPRL2
3 cellular response to amino acid starvation GO:0034198 9.13 NPRL3 NPRL2 DEPDC5
4 negative regulation of TOR signaling GO:0032007 8.8 NPRL3 NPRL2 DEPDC5

Molecular functions related to Epilepsy, Familial Focal, with Variable Foci 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 GTPase activator activity GO:0005096 8.8 NPRL3 NPRL2 DEPDC5

Sources for Epilepsy, Familial Focal, with Variable Foci 1

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