MCID: HYP097
MIFTS: 52

Hyperekplexia

Categories: Rare diseases, Genetic diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Hyperekplexia

MalaCards integrated aliases for Hyperekplexia:

Name: Hyperekplexia 12 23 24 25 56 29 52 14
Hereditary Hyperekplexia 12 50 25 56
Startle Disease, Familial 23 50 24
Startle Syndrome 23 24 25
Kok Disease 12 50 56
Congenital Stiff Man Syndrome 12 56
Hyperekplexia, Hereditary 23 24
Familial Startle Disease 12 56
Hereditary Hyperexplexia 56 69
Stiff-Baby Syndrome 50 25
Sthe 50 25
Stiff-Person Syndrome, Congenital 50
Congenital Stiff-Person Syndrome 25
Stiff-Man Syndrome, Congenital 50
Startle Reaction, Exaggerated 50
Congenital Stiff-Man Syndrome 25
Exaggerated Startle Reaction 50
Hyperexplexia Hereditary 50
Hyperekplexia Hereditary 29
Familial Hyperekplexia 25
Stiff-Person Syndrome 69
Stiff Baby Syndrome 56
Startle Disease 12

Characteristics:

Orphanet epidemiological data:

56
hereditary hyperekplexia
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

GeneReviews:

23
Penetrance Overall, the penetrance of hyperekplexia is 100%; however, in one family a mother who had the same variant as her two affected children was asymptomatic [kwok et al 2001]...

Classifications:



External Ids:

Disease Ontology 12 DOID:0060695
ICD10 33 G25.8
Orphanet 56 ORPHA3197
UMLS via Orphanet 70 C1835614
ICD10 via Orphanet 34 G25.8

Summaries for Hyperekplexia

NIH Rare Diseases : 50 hereditary hyperekplexia is an inherited condition that is usually evident in infants. symptoms include increased muscle tone (hypertonia) and an exaggerated startle reaction to unexpected stimuli, especially loud noises. following the startle reaction, infants experience a brief period in which they are very rigid and unable to move. during these rigid periods, some infants stop breathing, which can be fatal. this condition may explain some cases of sudden infant death syndrome (sids). stiffness typically fade by age 1. however, older individuals with this condition may still startle easily and have periods of rigidity. others may have a low tolerance for crowded places and loud noises. this condition has different inheritance patterns and is associated with mutations in at least five genes. treatment is mainly with the use of the drug clonazepam which is very effective in reducing symptoms. last updated: 2/19/2016

MalaCards based summary : Hyperekplexia, also known as hereditary hyperekplexia, is related to hyperekplexia 2, autosomal recessive and hyperekplexia 3, and has symptoms including fever, muscle rigidity and opisthotonus. An important gene associated with Hyperekplexia is GLRA1 (Glycine Receptor Alpha 1), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Ion channel transport. The drugs Glycine and Neurotransmitter Agents have been mentioned in the context of this disorder. Affiliated tissues include brain, heart and eye, and related phenotypes are behavior/neurological and mortality/aging

Disease Ontology : 12 A nervous system disease characterized by an exaggerated startle response to sudden, unexpected auditory or tactile stimuli and hypertonia.

Genetics Home Reference : 25 Hereditary hyperekplexia is a condition in which affected infants have increased muscle tone (hypertonia) and an exaggerated startle reaction to unexpected stimuli, especially loud noises. Following the startle reaction, infants experience a brief period in which they are very rigid and unable to move. During these rigid periods, some infants stop breathing, which, if prolonged, can be fatal. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of unexplained death in babies younger than 1 year. Infants with hereditary hyperekplexia have hypertonia at all times, except when they are sleeping.

Wikipedia : 72 Hyperekplexia (\"exaggerated surprise\") is a neurologic disorder classically characterised by... more...

GeneReviews: NBK1260

Related Diseases for Hyperekplexia

Diseases in the Hyperekplexia family:

Hyperekplexia 2, Autosomal Recessive Hyperekplexia, Hereditary 1, Autosomal Dominant or Recessive
Hyperekplexia 3 Hyperekplexia 1
Arhgef9-Related Hyperekplexia Glra1-Related Hyperekplexia
Glrb-Related Hyperekplexia Gphn-Related Hyperekplexia
Slc6a5-Related Hyperekplexia Sporadic Hyperekplexia

Diseases related to Hyperekplexia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 41)
id Related Disease Score Top Affiliating Genes
1 hyperekplexia 2, autosomal recessive 12.1
2 hyperekplexia 3 12.1
3 hyperekplexia, hereditary 1, autosomal dominant or recessive 12.1
4 hyperekplexia 1 12.0
5 sporadic hyperekplexia 11.9
6 slc6a5-related hyperekplexia 11.7
7 arhgef9-related hyperekplexia 11.7
8 glra1-related hyperekplexia 11.7
9 glrb-related hyperekplexia 11.7
10 gphn-related hyperekplexia 11.7
11 epileptic encephalopathy, early infantile, 8 11.4
12 molybdenum cofactor deficiency 11.1
13 stiff-person syndrome 11.0
14 epileptic encephalopathy, early infantile, 17 10.7
15 neuropathy, distal hereditary motor, type va 10.4 GARS GPHN
16 atrial tachyarrhythmia with short pr interval 10.3 GLRA1 GLRB GPHN
17 monogenic diabetes 10.2 GLRA1 GPHN MOCS1
18 adult choroid plexus cancer 10.2 GLRA1 TBC1D24
19 adolescence-adult electroclinical syndrome 10.1 GABRG2 TBC1D24
20 3-methylcrotonyl-coa carboxylase deficiency 10.0 GABRG2 TBC1D24
21 spasticity 9.9
22 spastic paraparesis 9.9
23 encephalopathy 9.8
24 microcephaly 9.8
25 epilepsy 9.8
26 neuronitis 9.8
27 erythermalgia, primary 9.8 GABRG2 SCN9A TBC1D24
28 gaba aminotransferase deficiency 9.8 GABRG2 SCN9A TBC1D24
29 early onset absence epilepsy 9.8 GABRG2 TBC1D24
30 inguinal hernia 9.7
31 status epilepticus 9.7
32 startle epilepsy 9.7
33 cerebritis 9.7
34 sudden infant death syndrome 9.7
35 muscular dystrophy 9.7
36 isolated sulfite oxidase deficiency 9.7
37 intellectual disability 9.7
38 sulfite oxidase deficiency 9.7
39 sleep apnea 9.7
40 obstructive sleep apnea 9.7
41 familial hypocalciuric hypercalcemia 4.8 ADRA1D ARHGEF9 DPP6 GABRG2 GARS GLRA1

Graphical network of the top 20 diseases related to Hyperekplexia:



Diseases related to Hyperekplexia

Symptoms & Phenotypes for Hyperekplexia

UMLS symptoms related to Hyperekplexia:


fever, muscle rigidity, opisthotonus, hyperexplexia, increased sweating, myoclonus

MGI Mouse Phenotypes related to Hyperekplexia:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.03 GPHN SCN9A SLC6A2 SLC6A5 SLC6A9 SLC7A10
2 mortality/aging MP:0010768 9.9 GABRG2 GARS GLRA1 GLRB GPHN SCN9A
3 muscle MP:0005369 9.5 ADRA1D GARS GLRA1 GLRB SLC6A5 SLC6A9
4 nervous system MP:0003631 9.44 ADRA1D ARHGEF9 DPP6 GABRG2 GARS GLRA1

Drugs & Therapeutics for Hyperekplexia

Drugs for Hyperekplexia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Glycine Approved, Nutraceutical, Vet_approved 56-40-6 750
2 Neurotransmitter Agents

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Effects of Mutations of the Glycine Gene Associated With Hyperekplexia on Central Pain Processing Terminated NCT01476514

Search NIH Clinical Center for Hyperekplexia

Genetic Tests for Hyperekplexia

Genetic tests related to Hyperekplexia:

id Genetic test Affiliating Genes
1 Hyperekplexia 29 24 SLC6A5
2 Hyperekplexia Hereditary 29

Anatomical Context for Hyperekplexia

MalaCards organs/tissues related to Hyperekplexia:

39
Brain, Heart, Eye, Cortex

Publications for Hyperekplexia

Articles related to Hyperekplexia:

(show top 50) (show all 173)
id Title Authors Year
1
Hyperekplexia: A forgotten diagnosis clinched by next-generation sequencing. ( 28879899 )
2017
2
Sporadic Hyperekplexia Plus Syndrome. ( 28553377 )
2017
3
Clinical and Electrophysiological Findings in Two Siblings with Familial Hyperekplexia. ( 28566967 )
2017
4
Familiar Hyperekplexia, a Potential Cause of Cautious Gait: A New Korean Case and a Systematic Review of Phenotypes. ( 28122427 )
2017
5
Teaching Video NeuroImages: Hyperekplexia: A syndrome of pathologic startle responses. ( 28348128 )
2017
6
Hyperekplexia, microcephaly and simplified gyral pattern caused by novel ASNS mutations, case report. ( 27422383 )
2016
7
Hyperekplexia: Report on phenotype and genotype of 16 Jordanian patients. ( 27843043 )
2016
8
Investigating the Mechanism by Which Gain-of-function Mutations to the I+1 Glycine Receptor Cause Hyperekplexia. ( 27226610 )
2016
9
A de novo CTNNB1 nonsense mutation associated with syndromic atypical hyperekplexia, microcephaly and intellectual disability: a case report. ( 26968164 )
2016
10
Disturbed neuronal ER-Golgi sorting of unassembled glycine receptors suggests altered subcellular processing is a cause of human hyperekplexia. ( 25568133 )
2015
11
Anesthetic management of a parturient with hyperekplexia. ( 25867194 )
2015
12
Molecular basis of the dominant negative effect of a glycine transporter 2 mutation associated with hyperekplexia. ( 25480793 )
2015
13
Molecular basis of a new form of hyperekplexia. ( 26531557 )
2015
14
Disturbances of Ligand Potency and Enhanced Degradation of the Human Glycine Receptor at Affected Positions G160 and T162 Originally Identified in Patients Suffering from Hyperekplexia. ( 26733802 )
2015
15
Infantile spasms and hyperekplexia associated with isolated sulfite oxidase deficiency. ( 24756183 )
2014
16
Hyperekplexia: A Chinese Adolescent With 2 Novel Mutations of the GLRA1 Gene. ( 23143726 )
2014
17
A confusing coincidence: neonatal hypoglycemic seizures and hyperekplexia. ( 24782896 )
2014
18
The impact of human hyperekplexia mutations on glycine receptor structure and function. ( 24405574 )
2014
19
Sporadic hyperekplexia presenting with an ataxic gait. ( 24054400 )
2014
20
Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease. ( 24390226 )
2014
21
Novel mutations in the glycine receptor alpha subunit gene in two sisters with hyperekplexia. ( 25079583 )
2014
22
Clobazam-Clonazepam Combination Effective for Stimulus-Induced Falling in Hyperekplexia. ( 24453146 )
2014
23
Neonatal hyperekplexia with homozygous p.R392H mutation in GLRA1. ( 25036534 )
2014
24
Identification of a novel missense GLRA1 gene mutation in hyperekplexia: a case report. ( 24969041 )
2014
25
Clinical and genetic investigation of 17 Japanese patients with hyperekplexia. ( 25356525 )
2014
26
Ethnicity can predict GLRA1 genotypes in hyperekplexia. ( 24970905 )
2014
27
Hyperekplexia: overexcitable and underdiagnosed. ( 25407752 )
2014
28
A Startling Case of Neonatal Hyperekplexia Responsive to Levetiracetam: A New Alternative in Management? ( 23034981 )
2013
29
Analysis of hyperekplexia mutations identifies transmembrane domain rearrangements that mediate glycine receptor activation. ( 24097980 )
2013
30
Glycine receptor mouse mutants: model systems for human hyperekplexia. ( 23941355 )
2013
31
GLRB is the third major gene of effect in hyperekplexia. ( 23184146 )
2013
32
A 14-year-old girl with hyperekplexia having GLRB mutations. ( 23182654 )
2013
33
New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms. ( 24108130 )
2013
34
Genotype-phenotype correlations in hyperekplexia: apnoeas, learning difficulties and speech delay. ( 24030948 )
2013
35
Clinical features and genetic analysis of children with hyperekplexia in Korea. ( 22532536 )
2013
36
The GLRA1 missense mutation W170S associates lack of Zn2+ potentiation with human hyperekplexia. ( 24198360 )
2013
37
A new hyperekplexia family with a recessive frameshift mutation in the GLRA1 gene. ( 22290764 )
2012
38
Novel mutation in GLRB in a large family with hereditary hyperekplexia. ( 21391991 )
2012
39
Novel mutation of GLRA1 in Omani families with hyperekplexia and mild mental retardation. ( 22264702 )
2012
40
Function of hyperekplexia-causing I+1R271Q/L glycine receptors is restored by shifting the affected residue out of the allosteric signalling pathway. ( 21955162 )
2012
41
A novel syndrome of lethal familial hyperekplexia associated with brain malformation. ( 23101555 )
2012
42
A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2. ( 22753417 )
2012
43
Hyperekplexia masquerading as epilepsy. ( 21222052 )
2011
44
Hyperekplexia: treatment of a severe phenotype and review of the literature. ( 21515498 )
2011
45
Ectodermal, skeletal, and genitourinary abnormalities with neonatal hyperekplexia. ( 21481749 )
2011
46
I^ Subunit M2-M3 loop conformational changes are uncoupled from I+1 I^ glycine receptor channel gating: implications for human hereditary hyperekplexia. ( 22132222 )
2011
47
Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia. ( 20631190 )
2010
48
Sinus node paucity in hyperekplexia. ( 21220806 )
2010
49
Hyperekplexia in a neonate: a novel finding in Fukuyama type congenital muscular dystrophy. ( 19852435 )
2009
50
Recessive hyperekplexia mutations of the glycine receptor alpha1 subunit affect cell surface integration and stability. ( 19732286 )
2009

Variations for Hyperekplexia

ClinVar genetic disease variations for Hyperekplexia:

6 (show all 20)
id Gene Variation Type Significance SNP ID Assembly Location
1 GLRA1 NM_001146040.1(GLRA1): c.896G> T (p.Arg299Leu) single nucleotide variant Pathogenic rs121918408 GRCh37 Chromosome 5, 151230967: 151230967
2 GLRA1 NM_001146040.1(GLRA1): c.896G> A (p.Arg299Gln) single nucleotide variant Pathogenic rs121918408 GRCh37 Chromosome 5, 151230967: 151230967
3 GLRA1 NM_001146040.1(GLRA1): c.815T> A (p.Ile272Asn) single nucleotide variant Pathogenic rs121918409 GRCh37 Chromosome 5, 151231048: 151231048
4 GLRA1 NM_001146040.1(GLRA1): c.920A> G (p.Tyr307Cys) single nucleotide variant Pathogenic rs121918410 GRCh37 Chromosome 5, 151208621: 151208621
5 GLRA1 NM_001146040.1(GLRA1): c.882G> C (p.Gln294His) single nucleotide variant Pathogenic rs121918411 GRCh37 Chromosome 5, 151230981: 151230981
6 GLRA1 NM_001146040.1(GLRA1): c.910A> G (p.Lys304Glu) single nucleotide variant Pathogenic rs121918412 GRCh37 Chromosome 5, 151230953: 151230953
7 GLRA1 NM_001146040.1(GLRA1): c.832C> A (p.Pro278Thr) single nucleotide variant Pathogenic rs121918413 GRCh37 Chromosome 5, 151231031: 151231031
8 GLRA1 NM_001146040.1(GLRA1): c.690C> A (p.Tyr230Ter) single nucleotide variant Pathogenic rs121918415 GRCh37 Chromosome 5, 151234608: 151234608
9 GLRA1 NM_001146040.1(GLRA1): c.862G> A (p.Val288Met) single nucleotide variant Pathogenic rs121918416 GRCh37 Chromosome 5, 151231001: 151231001
10 GLRA1 NM_001146040.1(GLRA1): c.777C> G (p.Ser259Arg) single nucleotide variant Pathogenic rs121918417 GRCh37 Chromosome 5, 151231086: 151231086
11 GLRA1 NM_001146040.1(GLRA1): c.(?_-287)_(912+?)del deletion Pathogenic
12 GLRA1 NM_001146040.1(GLRA1): c.971C> A (p.Ser324Ter) single nucleotide variant Pathogenic rs121918418 GRCh37 Chromosome 5, 151208570: 151208570
13 GLRA1 NM_001146040.1(GLRA1): c.884G> A (p.Ser295Asn) single nucleotide variant Pathogenic rs267606848 GRCh37 Chromosome 5, 151230979: 151230979
14 GLRA1 NM_001146040.1(GLRA1): c.299G> A (p.Arg100His) single nucleotide variant Pathogenic rs281864914 GRCh37 Chromosome 5, 151239523: 151239523
15 GLRA1 NM_001146040.1(GLRA1): c.737G> A (p.Arg246Gln) single nucleotide variant Pathogenic rs281864916 GRCh37 Chromosome 5, 151231126: 151231126
16 GLRA1 NM_001146040.1(GLRA1): c.801G> C (p.Trp267Cys) single nucleotide variant Pathogenic rs281864917 GRCh37 Chromosome 5, 151231062: 151231062
17 GLRA1 NM_001146040.1(GLRA1): c.892T> A (p.Ser298Thr) single nucleotide variant Pathogenic rs281864920 GRCh37 Chromosome 5, 151230971: 151230971
18 GLRA1 NM_001146040.1(GLRA1): c.920A> C (p.Tyr307Ser) single nucleotide variant Pathogenic rs121918410 GRCh37 Chromosome 5, 151208621: 151208621
19 GLRA1 NM_001146040.1(GLRA1): c.921delT (p.Tyr307Terfs) deletion Pathogenic rs281864921 GRCh37 Chromosome 5, 151208620: 151208620
20 GLRA1 NM_000171.3(GLRA1): c.(?_-287)_697+?del deletion Pathogenic GRCh38 Chromosome 5, 151855040: 151924836

Copy number variations for Hyperekplexia from CNVD:

7
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 194977 5 147200000 152100000 Deletion GLRA1 Hyperekplexia

Expression for Hyperekplexia

Search GEO for disease gene expression data for Hyperekplexia.

Pathways for Hyperekplexia

Pathways related to Hyperekplexia according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.69 ARHGEF9 GABRG2 GLRA1 GLRB SLC6A2 SLC6A5
2
Show member pathways
11.95 ARHGEF9 GABRG2 GLRA1 GLRB
3 11.66 SLC6A2 SLC6A5 SLC6A9
4 10.62 ADRA1D SLC6A2
5 10.57 GPHN MOCS1
6
Show member pathways
10.55 ARHGEF9 GABRG2 GLRA1 GLRB

GO Terms for Hyperekplexia

Cellular components related to Hyperekplexia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 cell junction GO:0030054 9.8 GABRG2 GLRA1 GLRB GPHN TBC1D24
2 synapse GO:0045202 9.73 GABRG2 GLRA1 GLRB GPHN
3 cell projection GO:0042995 9.73 GABRG2 GARS GLRA1 GLRB GPHN SCN9A
4 plasma membrane GO:0005886 9.73 ADRA1D DPP6 GABRG2 GLRA1 GLRB GPHN
5 dendrite GO:0030425 9.67 GABRG2 GLRA1 GLRB GPHN
6 postsynaptic membrane GO:0045211 9.62 GABRG2 GLRA1 GLRB GPHN
7 chloride channel complex GO:0034707 9.33 GABRG2 GLRA1 GLRB
8 integral component of plasma membrane GO:0005887 9.28 ADRA1D GABRG2 GLRA1 GLRB SCN9A SLC6A2

Biological processes related to Hyperekplexia according to GeneCards Suite gene sharing:

(show all 17)
id Name GO ID Score Top Affiliating Genes
1 transport GO:0006810 9.91 GABRG2 GLRA1 GLRB SCN9A SEC24D SLC6A2
2 chloride transmembrane transport GO:1902476 9.69 GABRG2 GLRA1 GLRB
3 chloride transport GO:0006821 9.67 GABRG2 GLRA1 GLRB
4 adult walking behavior GO:0007628 9.57 GLRA1 GLRB
5 amino acid transmembrane transport GO:0003333 9.56 SLC6A9 SLC7A10
6 neuromuscular process GO:0050905 9.55 GLRA1 GLRB
7 ion transmembrane transport GO:0034220 9.55 ARHGEF9 GABRG2 GLRA1 GLRB SCN9A
8 acrosome reaction GO:0007340 9.54 GLRA1 GLRB
9 neurotransmitter transport GO:0006836 9.54 SLC6A2 SLC6A5 SLC6A9
10 startle response GO:0001964 9.52 GLRA1 GLRB
11 righting reflex GO:0060013 9.48 GLRA1 GLRB
12 glycine transport GO:0015816 9.46 SLC6A5 SLC6A9
13 molybdopterin cofactor biosynthetic process GO:0032324 9.43 GPHN MOCS1
14 Mo-molybdopterin cofactor biosynthetic process GO:0006777 9.4 GPHN MOCS1
15 chemical synaptic transmission GO:0007268 9.35 GABRG2 GLRA1 GLRB SLC6A2 SLC6A5
16 gamma-aminobutyric acid receptor clustering GO:0097112 9.32 GLRB GPHN
17 synaptic transmission, glycinergic GO:0060012 8.8 GLRA1 GLRB SLC6A5

Molecular functions related to Hyperekplexia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 symporter activity GO:0015293 9.63 SLC6A2 SLC6A5 SLC6A9
2 chloride channel activity GO:0005254 9.58 GABRG2 GLRA1 GLRB
3 neurotransmitter:sodium symporter activity GO:0005328 9.48 SLC6A5 SLC6A9
4 glycine binding GO:0016594 9.43 GLRA1 GLRB
5 extracellular ligand-gated ion channel activity GO:0005230 9.43 GABRG2 GLRA1 GLRB
6 glycine transmembrane transporter activity GO:0015187 9.37 SLC6A5 SLC6A9
7 extracellular-glycine-gated chloride channel activity GO:0016934 9.32 GLRA1 GLRB
8 extracellular-glycine-gated ion channel activity GO:0016933 8.96 GLRA1 GLRB
9 ion channel activity GO:0005216 8.85 SCN9A
10 glycine:sodium symporter activity GO:0015375 8.62 SLC6A5 SLC6A9

Sources for Hyperekplexia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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