FEB8
MCID: FBR070
MIFTS: 31

Febrile Seizures, Familial, 8 (FEB8)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Febrile Seizures, Familial, 8

MalaCards integrated aliases for Febrile Seizures, Familial, 8:

Name: Febrile Seizures, Familial, 8 57 74
Generalized Epilepsy with Febrile Seizures Plus 3 74 29 6
Epilepsy, Childhood Absence 2 74 29 6
Familial Febrile Seizures 8 12 29 6
Feb8 57 12 74
Epilepsy, Generalized, with Febrile Seizures Plus, Type 3 57 40
Familial Febrile Convulsions 8 12 74
Epilepsy, Childhood Absence, Susceptibility to, 2 13
Epilepsy, Childhood Absence, Type 2 40
Gefs+ Type 3 74
Gefsp3 74
Gefs+3 74
Eca2 74

Characteristics:

OMIM:

57
Miscellaneous:
incomplete penetrance
highly variable phenotype, even within families
onset of febrile seizures in the first year of life
onset of absence seizures in childhood
seizures often remit later in childhood or adolescence
seizures may persist

Inheritance:
autosomal dominant


HPO:

32
febrile seizures, familial, 8:
Inheritance autosomal dominant inheritance heterogeneous
Onset and clinical course childhood onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0111298

Summaries for Febrile Seizures, Familial, 8

UniProtKB/Swiss-Prot : 74 Epilepsy, childhood absence 2: A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic- clonic seizures often develop in adolescence. Some individuals manifest febrile seizures. Absence seizures may either remit or persist into adulthood. Febrile seizures, familial, 8: Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. Generalized epilepsy with febrile seizures plus 3: A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity.

MalaCards based summary : Febrile Seizures, Familial, 8, also known as generalized epilepsy with febrile seizures plus 3, is related to ataxia and polyneuropathy, adult-onset and tremor, and has symptoms including absence seizures An important gene associated with Febrile Seizures, Familial, 8 is GABRG2 (Gamma-Aminobutyric Acid Type A Receptor Gamma2 Subunit). Affiliated tissues include bone and pancreas, and related phenotypes are generalized tonic-clonic seizures and eeg with polyspike wave complexes

Disease Ontology : 12 A familial febrile seizures that has material basis in heterozygous mutation in GABRG2 on chromosome 5q34.

OMIM : 57 Mutations in the GABRG2 gene cause a spectrum of seizure disorders, ranging from early-onset isolated febrile seizures (FS) to childhood absence epilepsy (CAE) to generalized epilepsy with febrile seizures plus, type 3 (GEFS+3), which tends to represent a more severe phenotype. Patients with isolated febrile seizures usually have onset in the first year of life and show spontaneous remission by age 6 years. Many of these patients may later develop absence seizures, which may also spontaneously remit, whereas a few may continue to have various types of febrile and afebrile seizures that persist beyond childhood, consistent with GEFS+. There is phenotypic variability in the seizure type, even within a family carrying the same mutation, suggesting that other loci may be involved (summary by Singh et al., 1999 and Marini et al., 2003). For a phenotypic description and a discussion of genetic heterogeneity of familial febrile seizures, see 121210. For a general phenotypic description and a discussion of genetic heterogeneity of GEFS+, see 604233. For a phenotypic description and discussion of genetic heterogeneity of childhood absence epilepsy, see 600131. (607681)

Related Diseases for Febrile Seizures, Familial, 8

Diseases in the Febrile Seizures family:

Febrile Seizures, Familial, 1 Febrile Seizures, Familial, 2
Febrile Seizures, Familial, 4 Febrile Seizures, Familial, 8
Febrile Seizures, Familial, 6 Febrile Seizures, Familial, 5
Febrile Seizures, Familial, 7 Febrile Seizures, Familial, 9
Febrile Seizures, Familial, 10 Febrile Seizures, Familial, 11
Familial Febrile Seizures

Diseases related to Febrile Seizures, Familial, 8 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 ataxia and polyneuropathy, adult-onset 10.2
2 tremor 10.2

Symptoms & Phenotypes for Febrile Seizures, Familial, 8

Human phenotypes related to Febrile Seizures, Familial, 8:

32
# Description HPO Frequency HPO Source Accession
1 generalized tonic-clonic seizures 32 HP:0002069
2 eeg with polyspike wave complexes 32 HP:0002392
3 absence seizure 32 HP:0002121
4 febrile seizures 32 HP:0002373
5 eeg with spike-wave complexes (>3.5 hz) 32 HP:0010849

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
febrile seizures
generalized tonic-clonic seizures (often develop in adolescence)
absence seizures (in some patients)
learning disabilities (rare)
3-4-hz spike and multispike slow wave complexes seen on eeg

Clinical features from OMIM:

607681

UMLS symptoms related to Febrile Seizures, Familial, 8:


absence seizures

Drugs & Therapeutics for Febrile Seizures, Familial, 8

Search Clinical Trials , NIH Clinical Center for Febrile Seizures, Familial, 8

Genetic Tests for Febrile Seizures, Familial, 8

Genetic tests related to Febrile Seizures, Familial, 8:

# Genetic test Affiliating Genes
1 Epilepsy, Childhood Absence 2 29 GABRG2
2 Familial Febrile Seizures 8 29
3 Generalized Epilepsy with Febrile Seizures Plus 3 29

Anatomical Context for Febrile Seizures, Familial, 8

MalaCards organs/tissues related to Febrile Seizures, Familial, 8:

41
Bone, Pancreas

Publications for Febrile Seizures, Familial, 8

Articles related to Febrile Seizures, Familial, 8:

(show all 44)
# Title Authors PMID Year
1
Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. 8 71
23708187 2013
2
A novel GABRG2 mutation associated with febrile seizures. 8 71
16924025 2006
3
A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions. 8 71
12117362 2002
4
Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus. 8 71
11748509 2002
5
Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures. 8 71
11326275 2001
6
First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene. 8 71
11326274 2001
7
Generalized epilepsy with febrile seizures plus: a common childhood-onset genetic epilepsy syndrome. 8 71
9894880 1999
8
De novo GABRG2 mutations associated with epileptic encephalopathies. 71
27864268 2017
9
Agonist-dependent endocytosis of γ-aminobutyric acid type A (GABAA) receptors revealed by a γ2(R43Q) epilepsy mutation. 71
23935098 2013
10
Reduced cortical inhibition in a mouse model of familial childhood absence epilepsy. 8
17947380 2007
11
A gamma 2(R43Q) mutation, linked to epilepsy in humans, alters GABAA receptor assembly and modifies subunit composition on the cell surface. 71
17148443 2007
12
Why does fever trigger febrile seizures? GABAA receptor gamma2 subunit mutations associated with idiopathic generalized epilepsies have temperature-dependent trafficking deficiencies. 71
16510738 2006
13
A GABAA receptor mutation linked to human epilepsy (gamma2R43Q) impairs cell surface expression of alphabetagamma receptors. 71
15342642 2004
14
Childhood absence epilepsy and febrile seizures: a family with a GABA(A) receptor mutation. 8
12477709 2003
15
GABA receptor function and epilepsy. 8
10514838 1999
16
Concordance of clinical forms of epilepsy in families with several affected members. Italian League Against Epilepsy Genetic Collaborative Group. 8
8404731 1993
17
Beneficial Effects of Ethyl-Cyanoacrylate Coating Against Candida Albicans Biofilm Formation. 38
31166390 2019
18
The renin-angiotensin system as a target to solve the riddle of endocrine pancreas homeostasis. 38
30404071 2019
19
The Cuticle Mutant eca2 Modifies Plant Defense Responses to Biotrophic and Necrotrophic Pathogens and Herbivory Insects. 38
29130376 2018
20
Application of phage therapy during bivalve depuration improves Escherichia coli decontamination. 38
27697159 2017
21
Characterization and in vitro evaluation of new bacteriophages for the biocontrol of Escherichia coli. 38
27756632 2017
22
Mapping of equine cerebellar abiotrophy to ECA2 and identification of a potential causative mutation affecting expression of MUTYH. 38
21126570 2011
23
Fine mapping of a quantitative trait locus for osteochondrosis on horse chromosome 2. 38
21070281 2010
24
Hypertrophied myocardium is more dependent on extracellular calcium than the normal cardiac muscle. 38
20671609 2010
25
Fine mapping a quantitative trait locus on horse chromosome 2 associated with radiological signs of navicular disease in Hanoverian warmblood horses. 38
19496769 2009
26
Whole-genome scan for guttural pouch tympany in Arabian and German warmblood horses. 38
19703122 2009
27
ECA3, a Golgi-localized P2A-type ATPase, plays a crucial role in manganese nutrition in Arabidopsis. 38
18024560 2008
28
Review of genetic aspects of radiological alterations in the navicular bone of the horse. 38
18077930 2007
29
Genome-wide search for microsatellite markers associated with radiologic alterations in the navicular bone of Hanoverian warmblood horses. 38
17551792 2007
30
Numerical chromosomal abnormalities in equine embryos produced in vivo and in vitro. 38
15948165 2005
31
Mapping of 13 horse genes by fluorescence in-situ hybridization (FISH) and somatic cell hybrid analysis. 38
11272792 2001
32
The effect of caffeine on p53-dependent radioresponses in undifferentiated mouse embryonal carcinoma cells after X-ray and UV-irradiations. 38
11210826 2000
33
A primary male autosomal linkage map of the horse genome. 38
9750194 1998
34
The production of platelet-activating factor (PAF) during hemodialysis with cuprophane membrane. Does the calcium concentration in the dialysate play any role on it? 38
8655220 1995
35
Synteny-mapping horse microsatellite markers using a heterohybridoma panel. 38
7793685 1995
36
States and functions of tyrosine residues in Escherichia coli asparaginase II. 38
7925369 1994
37
BOX DNA: a novel regulatory element related to embryonal carcinoma cell differentiation. 38
7902532 1993
38
Ca2+ binding to sarcoplasmic reticulum ATPase revisited. II. Equilibrium and kinetic evidence for a two-route mechanism. 38
8496160 1993
39
Site-specific mutagenesis of Escherichia coli asparaginase II. None of the three histidine residues is required for catalysis. 38
1521538 1992
40
Expression of tumor necrosis factor-alpha and -beta transcripts in embryonal carcinoma and trophoblast cell lines: inflammation-like state as possible regulatory mechanism for ontogenesis. 38
1756230 1991
41
Analysis of the binding proteins and activity of the long terminal repeat of Moloney murine leukemia virus during differentiation of mouse embryonal carcinoma cells. 38
2033663 1991
42
Expression of TNF-alpha and TNF-beta transcripts in murine embryonal carcinoma cells and trophoblast cell. 38
1842048 1991
43
Mechanism of suppression of the long terminal repeat of Moloney leukemia virus in mouse embryonal carcinoma cells. 38
2601693 1989
44
Development of ion channels and neurofilaments during neuronal differentiation of mouse embryonal carcinoma cell lines. 38
2479740 1989

Variations for Febrile Seizures, Familial, 8

ClinVar genetic disease variations for Febrile Seizures, Familial, 8:

6 (show top 50) (show all 75)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 GABRG2 NM_198903.2(GABRG2): c.937G> T (p.Gly313Ter) single nucleotide variant Pathogenic rs1469287853 5:161569217-161569217 5:162142211-162142211
2 GABRG2 NM_198903.2(GABRG2): c.797_801del (p.Ser265_Ser266insTer) deletion Pathogenic rs1554098222 5:161530940-161530944 5:162103934-162103938
3 GABRG2 NM_198903.2(GABRG2): c.1103A> T (p.Lys368Met) single nucleotide variant Pathogenic rs121909672 5:161576174-161576174 5:162149168-162149168
4 GABRG2 NM_198903.2(GABRG2): c.1312C> T (p.Gln438Ter) single nucleotide variant Pathogenic rs121909674 5:161580138-161580138 5:162153132-162153132
5 GABRG2 NM_198903.2(GABRG2): c.889+2T> G single nucleotide variant Pathogenic,risk factor 5:161531034-161531034 5:162104028-162104028
6 GABRG2 NM_198903.2(GABRG2): c.529C> G (p.Arg177Gly) single nucleotide variant Pathogenic rs267606837 5:161524845-161524845 5:162097839-162097839
7 GABRG2 NM_198903.2(GABRG2): c.1088G> A (p.Arg363Gln) single nucleotide variant Pathogenic rs397514737 5:161576159-161576159 5:162149153-162149153
8 GABRG2 NM_198903.2(GABRG2): c.1155del (p.Phe385fs) deletion Pathogenic 5:161576226-161576226 5:162149220-162149220
9 GABRG2 NM_198903.2(GABRG2): c.530del (p.Arg177fs) deletion Pathogenic rs878854144 5:161524846-161524846 5:162097840-162097840
10 GABRG2 NM_198903.2(GABRG2): c.316G> A (p.Ala106Thr) single nucleotide variant Pathogenic/Likely pathogenic rs796052505 5:161522557-161522557 5:162095551-162095551
11 GABRG2 NM_198903.2(GABRG2): c.245G> A (p.Arg82Gln) single nucleotide variant Pathogenic/Likely pathogenic rs121909673 5:161520971-161520971 5:162093965-162093965
12 GABRG2 NM_198903.2(GABRG2): c.824G> A (p.Trp275Ter) single nucleotide variant Likely pathogenic rs1554098226 5:161530967-161530967 5:162103961-162103961
13 GABRG2 NM_198903.2(GABRG2): c.1145del (p.Cys382fs) deletion Likely pathogenic rs1060501889 5:161576216-161576216 5:162149210-162149210
14 GABRG2 NM_198903.2(GABRG2): c.1181G> T (p.Gly394Val) single nucleotide variant Likely pathogenic rs1060501888 5:161576252-161576252 5:162149246-162149246
15 GABRG2 deletion Likely pathogenic
16 GABRG2 NM_198903.2(GABRG2): c.1273-2A> G single nucleotide variant Likely pathogenic rs1554101185 5:161580097-161580097 5:162153091-162153091
17 GABRG2 NM_198903.2(GABRG2): c.501C> A (p.Asn167Lys) single nucleotide variant Likely pathogenic 5:161524817-161524817 5:162097811-162097811
18 GABRG2 NM_198903.2(GABRG2): c.1042+6A> G single nucleotide variant Conflicting interpretations of pathogenicity rs375294947 5:161569328-161569328 5:162142322-162142322
19 GABRG2 NM_198903.2(GABRG2): c.11C> T (p.Pro4Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs375295110 5:161495016-161495016 5:162068010-162068010
20 GABRG2 NM_198903.2(GABRG2): c.1480C> T (p.Arg494Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs796052515 5:161580306-161580306 5:162153300-162153300
21 GABRG2 NM_198903.2(GABRG2): c.1440G> A (p.Gly480=) single nucleotide variant Conflicting interpretations of pathogenicity rs150727562 5:161580266-161580266 5:162153260-162153260
22 GABRG2 NM_198903.2(GABRG2): c.1292G> A (p.Arg431His) single nucleotide variant Conflicting interpretations of pathogenicity rs528036202 5:161580118-161580118 5:162153112-162153112
23 GABRG2 NM_198903.2(GABRG2): c.135C> T (p.Asp45=) single nucleotide variant Conflicting interpretations of pathogenicity rs375308385 5:161520861-161520861 5:162093855-162093855
24 GABRG2 NM_198903.2(GABRG2): c.269C> T (p.Thr90Met) single nucleotide variant Conflicting interpretations of pathogenicity rs1057520498 5:161522510-161522510 5:162095504-162095504
25 GABRG2 NM_198903.2(GABRG2): c.1120G> A (p.Ala374Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs398123523 5:161576191-161576191 5:162149185-162149185
26 GABRG2 NM_198903.2(GABRG2): c.1454G> T (p.Arg485Leu) single nucleotide variant Uncertain significance rs587780341 5:161580280-161580280 5:162153274-162153274
27 GABRG2 NM_198903.2(GABRG2): c.1047C> G (p.Ile349Met) single nucleotide variant Uncertain significance rs1554100910 5:161576118-161576118 5:162149112-162149112
28 GABRG2 NC_000005.9: g.(?_161528241)_(161582545_?)dup duplication Uncertain significance 5:161528241-161582545 5:162101235-162155539
29 GABRG2 NM_198903.2(GABRG2): c.71C> A (p.Thr24Lys) single nucleotide variant Uncertain significance rs1060501891 5:161495076-161495076 5:162068070-162068070
30 GABRG2 NM_198903.2(GABRG2): c.583C> A (p.His195Asn) single nucleotide variant Uncertain significance rs981863613 5:161528275-161528275 5:162101269-162101269
31 GABRG2 NM_198903.2(GABRG2): c.1127A> G (p.Asp376Gly) single nucleotide variant Uncertain significance rs1060501890 5:161576198-161576198 5:162149192-162149192
32 GABRG2 NM_198903.2(GABRG2): c.365A> G (p.Tyr122Cys) single nucleotide variant Uncertain significance rs1554097875 5:161524681-161524681 5:162097675-162097675
33 GABRG2 NM_198903.2(GABRG2): c.608C> G (p.Ser203Cys) single nucleotide variant Uncertain significance rs1334273668 5:161528300-161528300 5:162101294-162101294
34 GABRG2 NM_198903.2(GABRG2): c.17T> C (p.Ile6Thr) single nucleotide variant Uncertain significance 5:161495022-161495022 5:162068016-162068016
35 GABRG2 NM_198903.2(GABRG2): c.191G> A (p.Gly64Asp) single nucleotide variant Uncertain significance 5:161520917-161520917 5:162093911-162093911
36 GABRG2 NM_198903.2(GABRG2): c.579A> G (p.Gln193=) single nucleotide variant Uncertain significance 5:161528271-161528271 5:162101265-162101265
37 GABRG2 NM_198903.2(GABRG2): c.1072C> G (p.Leu358Val) single nucleotide variant Uncertain significance 5:161576143-161576143 5:162149137-162149137
38 GABRG2 NM_198903.2(GABRG2): c.353C> T (p.Ala118Val) single nucleotide variant Uncertain significance 5:161524669-161524669 5:162097663-162097663
39 GABRG2 NM_198903.2(GABRG2): c.530G> A (p.Arg177Gln) single nucleotide variant Uncertain significance 5:161524846-161524846 5:162097840-162097840
40 GABRG2 NM_198903.2(GABRG2): c.764G> C (p.Arg255Pro) single nucleotide variant Uncertain significance 5:161530907-161530907 5:162103901-162103901
41 GABRG2 NM_198903.2(GABRG2): c.41A> G (p.Tyr14Cys) single nucleotide variant Uncertain significance 5:161495046-161495046 5:162068040-162068040
42 GABRG2 NM_198903.2(GABRG2): c.810C> A (p.Gly270=) single nucleotide variant Uncertain significance 5:161530953-161530953 5:162103947-162103947
43 GABRG2 NM_198903.2(GABRG2): c.106G> A (p.Gly36Ser) single nucleotide variant Uncertain significance 5:161495111-161495111 5:162068105-162068105
44 GABRG2 NM_198903.2(GABRG2): c.455T> C (p.Phe152Ser) single nucleotide variant Uncertain significance 5:161524771-161524771 5:162097765-162097765
45 GABRG2 NM_198903.2(GABRG2): c.173C> A (p.Thr58Asn) single nucleotide variant Uncertain significance rs763218917 5:161520899-161520899 5:162093893-162093893
46 GABRG2 NM_198903.2(GABRG2): c.1087C> T (p.Arg363Trp) single nucleotide variant Uncertain significance rs796052510 5:161576158-161576158 5:162149152-162149152
47 GABRG2 NM_198903.2(GABRG2): c.1207C> T (p.Arg403Trp) single nucleotide variant Uncertain significance rs374512652 5:161576278-161576278 5:162149272-162149272
48 GABRG2 NM_198903.2(GABRG2): c.1208G> A (p.Arg403Gln) single nucleotide variant Uncertain significance rs780199000 5:161576279-161576279 5:162149273-162149273
49 GABRG2 NM_198903.2(GABRG2): c.1232A> C (p.Lys411Thr) single nucleotide variant Uncertain significance rs796052512 5:161576303-161576303 5:162149297-162149297
50 GABRG2 NM_198903.2(GABRG2): c.764G> T (p.Arg255Leu) single nucleotide variant Uncertain significance 5:161530907-161530907 5:162103901-162103901

UniProtKB/Swiss-Prot genetic disease variations for Febrile Seizures, Familial, 8:

74
# Symbol AA change Variation ID SNP ID
1 GABRG2 p.Arg82Gln VAR_014265 rs121909673

Expression for Febrile Seizures, Familial, 8

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GO Terms for Febrile Seizures, Familial, 8

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