MCID: HYP097
MIFTS: 51

Hyperekplexia malady

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

Aliases & Classifications for Hyperekplexia

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Sources:
22GeneReviews, 46NIH Rare Diseases, 23GeneTests, 24Genetics Home Reference, 52Orphanet, 25GTR, 48Novoseek, 66UMLS, 29ICD10 via Orphanet
See all MalaCards sources

Aliases & Descriptions for Hyperekplexia:

Name: Hyperekplexia 22 23 24 52 25 48
Hereditary Hyperekplexia 46 24 52 25
Startle Disease, Familial 22 46 23
Startle Syndrome 22 23 24
Hyperekplexia, Hereditary 22 23
Hereditary Hyperexplexia 52 66
Stiff-Baby Syndrome 46 24
Kok Disease 46 52
Sthe 46 24
Stiff-Person Syndrome, Congenital 46
Congenital Stiff-Person Syndrome 24
 
Stiff-Man Syndrome, Congenital 46
Congenital Stiff-Man Syndrome 24
Startle Reaction, Exaggerated 46
Congenital Stiff Man Syndrome 52
Exaggerated Startle Reaction 46
Hyperexplexia Hereditary 46
Familial Startle Disease 52
Familial Hyperekplexia 24
Stiff-Person Syndrome 66
Stiff Baby Syndrome 52

Characteristics:

Orphanet epidemiological data:

52
hyperekplexia:
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal

Classifications:



External Ids:

Orphanet52 ORPHA3197
ICD10 via Orphanet29 G25.8

Summaries for Hyperekplexia

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NIH Rare Diseases:46 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 hypertonia, hyperreflexia and limitation of joint mobility. An important gene associated with Hyperekplexia is SLC6A5 (Solute Carrier Family 6 Member 5), and among its related pathways are Ligand-gated ion channel transport and Ion channel transport. Affiliated tissues include bone, brain and heart, and related mouse phenotypes are behavior/neurological and nervous system.

Genetics Home Reference:24 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:69 Hyperekplexia (\"exaggerated surprise\") is a neurologic disorder classically characterised by... more...

GeneReviews summary for NBK1260

Related Diseases for Hyperekplexia

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Diseases in the Hyperekplexia family:

Hyperekplexia 2, Autosomal Recessive Hyperekplexia, Hereditary 1, Autosomal Dominant or Recessive
Hyperekplexia 3 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 34)
idRelated DiseaseScoreTop Affiliating Genes
1hyperekplexia 2, autosomal recessive12.1
2hyperekplexia 312.1
3hyperekplexia, hereditary 1, autosomal dominant or recessive12.1
4sporadic hyperekplexia12.0
5arhgef9-related hyperekplexia11.8
6glra1-related hyperekplexia11.8
7glrb-related hyperekplexia11.8
8gphn-related hyperekplexia11.8
9slc6a5-related hyperekplexia11.8
10epileptic encephalopathy, early infantile, 811.4
11epileptic encephalopathy, early infantile, 1710.9
12molybdenum cofactor deficiency10.5
13spastic paraparesis10.1
14spasticity10.1
15microcephaly10.0
16epilepsy10.0
17neuronitis10.0
18encephalopathy10.0
19deafness, autosomal recessive 1019.9GLRA1, GPHN
20cryptogenic organizing pneumonia9.8GLRA1, GLRB
21glycine encephalopathy9.8GARS, SLC6A5
22sudden infant death syndrome9.8
23sulfite oxidase deficiency9.8
24sleep apnea9.8
25obstructive sleep apnea9.8
26inguinal hernia9.8
27status epilepticus9.8
28cerebritis9.8
29muscular dystrophy9.8
30intellectual disability9.8
31startle epilepsy9.8
32myd88 deficiency9.6GLRA1, GLRB, GPHN
33complement component deficiency9.3GLRA1, GPHN, MOCS1
34ipex syndrome7.0ARHGEF9, GABRG2, GARS, GLRA1, GLRB, GPHN

Graphical network of the top 20 diseases related to Hyperekplexia:



Diseases related to hyperekplexia

Symptoms for Hyperekplexia

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HPO human phenotypes related to Hyperekplexia:

(show all 12)
id Description Frequency HPO Source Accession
1 hypertonia hallmark (90%) HP:0001276
2 hyperreflexia hallmark (90%) HP:0001347
3 limitation of joint mobility hallmark (90%) HP:0001376
4 incoordination hallmark (90%) HP:0002311
5 involuntary movements hallmark (90%) HP:0004305
6 gait disturbance typical (50%) HP:0001288
7 umbilical hernia typical (50%) HP:0001537
8 sleep disturbance typical (50%) HP:0002360
9 seizures occasional (7.5%) HP:0001250
10 joint dislocation occasional (7.5%) HP:0001373
11 abnormality of the hip bone occasional (7.5%) HP:0003272
12 cognitive impairment occasional (7.5%) HP:0100543

UMLS symptoms related to Hyperekplexia:


muscle rigidity, muscle spasticity, torticollis, cogwheel rigidity, opisthotonus, hyperexplexia, drop attack, increased sweating, abnormal muscle tone, anal sphincter atony, nuchal rigidity, myoclonus

Drugs & Therapeutics for Hyperekplexia

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

idNameStatusPhaseClinical TrialsCas NumberPubChem Id
1
rituximabPhase 21611174722-31-710201696
Synonyms:
AntiCD20
IDEC-102
IDEC-C2B8
 
Ig gamma-1 chain C region
MabThera
Mabthera
Rituxan
rituximab
2
GlycineNutraceutical19856-40-6750
Synonyms:
(1-13c)glycinato
(15N)Glycine
15527_RIEDEL
15527_SIAL
15743-44-9 (mono-potassium salt)
17829-66-2 (cobalt salt)
18875-39-3
2,2-dialkylglycines
2-Aminoacetate
2-Aminoacetic acid
2311-65-1
25718-94-9
29728-27-6 (monoammonium salt)
32817-15-5 (copper salt)
33226_RIEDEL
33226_SIAL
33242-26-1 (calcium salt)
35947-07-0 (calcium salt (2:1))
410225_SIAL
50046_FLUKA
50046_SIGMA
513-29-1 (sulfate (3:1))
52955-63-2
56-40-6
57678-19-0
6000-43-7 (hydrochloride)
6000-44-8 (mono-hydrochloride salt)
63183-41-5 (hydrochloride hydrogen carbonate)
71295-98-2 (phosphate (1:1))
7490-95-1 (hydrochloride (2:1)
7490-95-1 (hydrochloride (2:1))
7575-55-5
848646-45-7
87867-94-5
AB-131/40217813
AB1002628
AC1L19XW
AC1Q28JW
AC1Q53O0
AI3-04085
AKOS000119626
AMINOACETIC ACID 1.5% IN PLASTIC CONTAINER
AR-1A0345
AR-1A0532
Acide aminoacetique
Acide aminoacetique [INN-French]
Acido aminoacetico
Acido aminoacetico [INN-Spanish]
Acidum aminoaceticum
Acidum aminoaceticum [INN-Latin]
Aciport
Amino-Acetate
Amino-Acetic acid
Aminoacetate
Aminoacetic acid
Aminoazijnzuur
Aminoessigsaeure
Aminoethanoate
Aminoethanoic acid
Amitone
B72BA06C-60E9-4A83-A24A-A2D7F465BB65
BPBio1_001222
Biomol-NT_000195
C00037
CCRIS 5915
CHEBI:15428
CHEBI:15705
CHEBI:16228
CHEMBL773
CID750
CPD-8569
Corilin
D00011
DB00145
EINECS 200-272-2
 
FEMA No. 3287
FT-0083159
G
G0099
G0317
G5417_SIGMA
G5523_SIGMA
G7126_SIGMA
G7403_SIGMA
G8790_SIGMA
G8898_SIGMA
GLY (IUPAC abbrev)
GLYCINE 1.5% IN PLASTIC CONTAINER
GLYCINE, ACS
Glicina
Glicina [INN-Spanish]
Glicoamin
Gly
Glycin
Glycine
Glycine (JP15/USP)
Glycine [INN]
Glycine iron sulphate (1:1)
Glycine, homopolymer (VAN)
Glycine, labeled with carbon-14
Glycine, non-medical
Glycine-UL-14C hydrochloride
Glycinum
Glycinum [INN-Latin]
Glycocoll
Glycolixir
Glycosthene
Glykokoll
Glyzin
Gyn-Hydralin
Gyn-hydralin
H-Gly-OH
H2N-CH2-COOH
HSDB 495
Hampshire glycine
Hgly
InChI=1/C2H5NO2/c3-1-2(4)5/h1,3H2,(H,4,5
KST-1A2919
KST-1A8102
L-Glycine
L-alpha-amino acids
L001246
LS-218
Leimzucker
MolPort-000-871-607
NCGC00024503-01
NCGC00024503-02
NChemBio.2007.13-comp1
NSC 25936
NSC25936
P8791_SIGMA
Padil
Polyglycine II
S04-0135
Sucre de gelatine
Tocris-0219
UNII-TE7660XO1C
W328707_ALDRICH
WLN: Z1VQ
aminoacetic acid
an alpha amino acid ester
bmse000089
gly
glycine
nchem.554-comp2
nchembio.121-comp9
nchembio.145-comp33
nchembio.198-comp12
nchembio.265-comp9
nchembio.266-comp30
polyglycine

Interventional clinical trials:

idNameStatusNCT IDPhase
1Rituximab to Treat Stiff Person SyndromeCompletedNCT00091897Phase 2
2Stem Cell Transplantation for Stiff Person Syndrome (SPS)RecruitingNCT02282514Phase 1, Phase 2
3Intravenous Immunoglobulin (IVIg) for the Treatment of Stiff-Man Syndrome (SMS)CompletedNCT00001550Phase 1
4Cause, Development, and Progression of Stiff-Person SyndromeCompletedNCT00030940
5Effects of Mutations of the Glycine Gene Associated With Hyperekplexia on Central Pain ProcessingTerminatedNCT01476514

Search NIH Clinical Center for Hyperekplexia

Genetic Tests for Hyperekplexia

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Genetic tests related to Hyperekplexia:

id Genetic test Affiliating Genes
1 Hyperekplexia Hereditary25
2 Hyperekplexia25 23 SLC6A5

Anatomical Context for Hyperekplexia

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MalaCards organs/tissues related to Hyperekplexia:

34
Bone, Brain, Heart, Cortex, Eye

Animal Models for Hyperekplexia or affiliated genes

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MGI Mouse Phenotypes related to Hyperekplexia:

39
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053867.2ARHGEF9, GABRG2, GARS, GLRA1, GLRB, GPHN
2MP:00036316.9ARHGEF9, GABRG2, GARS, GLRA1, GLRB, GPHN

Publications for Hyperekplexia

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Articles related to Hyperekplexia:

(show top 50)    (show all 167)
idTitleAuthorsYear
1
Molecular basis of the dominant negative effect of a glycine transporter 2 mutation associated with hyperekplexia. (25480793)
2015
2
Disturbed neuronal ER-Golgi sorting of unassembled glycine receptors suggests altered subcellular processing is a cause of human hyperekplexia. (25568133)
2015
3
The impact of human hyperekplexia mutations on glycine receptor structure and function. (24405574)
2014
4
Hyperekplexia: A Chinese Adolescent With 2 Novel Mutations of the GLRA1 Gene. (23143726)
2014
5
Neonatal hyperekplexia with homozygous p.R392H mutation in GLRA1. (25036534)
2014
6
Novel mutations in the glycine receptor alpha subunit gene in two sisters with hyperekplexia. (25079583)
2014
7
Clinical features and genetic analysis of children with hyperekplexia in Korea. (22532536)
2013
8
Analysis of hyperekplexia mutations identifies transmembrane domain rearrangements that mediate glycine receptor activation. (24097980)
2013
9
Hyperekplexia: treatment of a severe phenotype and review of the literature. (21515498)
2011
10
I^ Subunit M2-M3 loop conformational changes are uncoupled from I+1 I^ glycine receptor channel gating: implications for human hereditary hyperekplexia. (22132222)
2011
11
Hyperekplexia masquerading as epilepsy. (21222052)
2011
12
Recessive hyperekplexia mutations of the glycine receptor alpha1 subunit affect cell surface integration and stability. (19732286)
2009
13
Identification of a de novo Lys304Gln mutation in the glycine receptor alpha-1 subunit gene in a Korean infant with hyperekplexia. (18175347)
2008
14
A novel GLRA1 mutation associated with an atypical hyperekplexia phenotype. (19073849)
2008
15
Bilateral inguinal hernia repair in a child with hyperekplexia. (17897277)
2007
16
Clinical and inheritance profiles of hyperekplexia in Jordan. (17715287)
2007
17
A novel GLRA1 mutation in a recessive hyperekplexia pedigree. (17534957)
2007
18
Hyperekplexia (startle disease) mimicking neonatal seizures: report of one case. (19653412)
2007
19
Hyperekplexia caused by dominant-negative suppression of glyra1 function. (17536053)
2007
20
Two Japanese families with hyperekplexia who have a Arg271Gln mutation in the glycine receptor alpha 1 subunit gene. (16478653)
2006
21
Neonatal hyperekplexia: the Stiff-Baby syndrome. (16820664)
2006
22
Molybdenum cofactor deficiency presenting as neonatal hyperekplexia: a clinical, biochemical and genetic study. (16429380)
2005
23
Two novel mutations of the glycine receptor gene in a Taiwanese hyperekplexia family. (15365143)
2004
24
Hereditary hyperekplexia caused by novel mutations of GLRA1 in Turkish families. (15771552)
2004
25
Sporadic major hyperekplexia in neonates and infants: clinical manifestations and outcome. (15246489)
2004
26
A novel mutation (R218Q) at the boundary between the N-terminal and the first transmembrane domain of the glycine receptor in a case of sporadic hyperekplexia. (12746425)
2003
27
A novel recessive hyperekplexia allele GLRA1 (S231R): genotyping by MALDI-TOF mass spectrometry and functional characterisation as a determinant of cellular glycine receptor trafficking. (11973623)
2002
28
Hyperekplexia mutation of glycine receptors: decreased gating efficacy with altered binding thermodynamics. (12123749)
2002
29
Statistical coassembly of glycine receptor alpha1 wildtype and the hyperekplexia mutant alpha1(P250T) in HEK 293 cells: impaired channel function is not dominant in the recombinant system. (12359314)
2002
30
Hyperekplexia: a treatable neurogenetic disease. (12427512)
2002
31
Compound heterozygosity and nonsense mutations in the alpha(1)-subunit of the inhibitory glycine receptor in hyperekplexia. (11702206)
2001
32
Opposing effects of molecular volume and charge at the hyperekplexia site alpha 1(P250) govern glycine receptor activation and desensitization. (11395484)
2001
33
Patients with the major and minor form of hyperekplexia differ with regards to disynaptic reciprocal inhibition between ankle flexor and extensor muscles. (11521151)
2001
34
Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an intracellular determinant of glycine receptor channel gating. (9920650)
1999
35
Hyperekplexia phenotype due to compound heterozygosity for GLRA1 gene mutations. (10514101)
1999
36
Hyperekplexia in a patient with a brainstem vascular anomaly. (10225359)
1999
37
Neonatal sporadic hyperekplexia: a rare and often unrecognized entity. (9134197)
1997
38
A novel mutation (Gln266-->His) in the alpha 1 subunit of the inhibitory glycine-receptor gene (GLRA1) in hereditary hyperekplexia. (8571969)
1996
39
A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors. (8651283)
1996
40
Physiological studies of spinal inhibitory pathways in patients with hereditary hyperekplexia. (8618680)
1996
41
Mutational analysis of familial and sporadic hyperekplexia. (7611730)
1995
42
Somatosensory evoked potentials and hyperekplexia outcome. (7746224)
1995
43
Complete heart block in nonfamilial hyperekplexia. (7779213)
1995
44
Hyperekplexia mutations of the glycine receptor unmask the inhibitory subsite for beta-amino-acids. (7542038)
1995
45
Hyperekplexia, a cause of neonatal apnea: a case report. (7625544)
1995
46
Hyperekplexia associated with apnea and sudden infant death syndrome. (8180653)
1994
47
Startle disease or hyperekplexia. (8224555)
1993
48
Hyperekplexia and stiff-baby syndrome: an identical neurological disorder? (8509269)
1993
49
Genetic and radiation hybrid mapping of the hyperekplexia region on chromosome 5q. (1334371)
1992
50
Neonatal hyperekplexia: a case report. (1396422)
1992

Variations for Hyperekplexia

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Copy number variations for Hyperekplexia from CNVD:

6
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
11949775147200000152100000DeletionGLRA1Hyperekplexia

Expression for genes affiliated with Hyperekplexia

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Search GEO for disease gene expression data for Hyperekplexia.

Pathways for genes affiliated with Hyperekplexia

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GO Terms for genes affiliated with Hyperekplexia

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

idNameGO IDScoreTop Affiliating Genes
1chloride channel complexGO:003470710.1GABRG2, GLRA1
2dendriteGO:00304259.2GLRA1, GLRB, GPHN
3postsynaptic membraneGO:00452118.9GABRG2, GLRA1, GLRB, GPHN
4cell junctionGO:00300548.6GABRG2, GLRA1, GLRB, GPHN

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

(show all 16)
idNameGO IDScoreTop Affiliating Genes
1gamma-aminobutyric acid receptor clusteringGO:009711210.3GLRB, GPHN
2acrosome reactionGO:000734010.3GLRA1, GLRB
3righting reflexGO:006001310.3GLRA1, GLRB
4neuromuscular processGO:005090510.2GLRA1, GLRB
5neuropeptide signaling pathwayGO:000721810.1GLRA1, GLRB
6protein heterooligomerizationGO:005129110.0GLRA1, GLRB
7ion transportGO:000681110.0GLRA1, GLRB
8synaptic transmission, glycinergicGO:006001210.0GLRA1, GLRB, SLC6A5
9regulation of membrane potentialGO:00423919.9GLRA1, GLRB
10molybdopterin cofactor biosynthetic processGO:00323249.9GPHN, MOCS1
11Mo-molybdopterin cofactor biosynthetic processGO:00067779.9GPHN, MOCS1
12chloride transmembrane transportGO:19024769.6GABRG2, GLRA1, GLRB
13startle responseGO:00019649.6GLRA1, GLRB
14adult walking behaviorGO:00076289.4GLRA1, GLRB
15ion transmembrane transportGO:00342208.9ARHGEF9, GABRG2, GLRA1, GLRB
16chemical synaptic transmissionGO:00072688.8GABRG2, GLRA1, GLRB, SLC6A5

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

idNameGO IDScoreTop Affiliating Genes
1extracellular-glycine-gated chloride channel activityGO:00169349.9GLRA1, GLRB
2extracellular-glycine-gated ion channel activityGO:00169339.9GLRA1, GLRB
3glycine bindingGO:00165949.7GLRA1, GLRB

Sources for Hyperekplexia

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
25GTR
26HGMD
27HMDB
28ICD10
29ICD10 via Orphanet
30ICD9CM
31IUPHAR
32KEGG
35MedGen
37MeSH
38MESH via Orphanet
39MGI
42NCI
43NCIt
44NDF-RT
47NINDS
48Novoseek
50OMIM
51OMIM via Orphanet
55PubMed
56QIAGEN
61SNOMED-CT via Orphanet
65Tumor Gene Family of Databases
66UMLS
67UMLS via Orphanet