MCID: MGR032
MIFTS: 37

Migraine, Familial Hemiplegic, 1

Categories: Genetic diseases, Rare diseases, Neuronal diseases

Aliases & Classifications for Migraine, Familial Hemiplegic, 1

MalaCards integrated aliases for Migraine, Familial Hemiplegic, 1:

Name: Migraine, Familial Hemiplegic, 1 57 75 13
Familial Hemiplegic Migraine Type 1 53 29 6
Fhm1 57 53 75
Mhp1 57 53 75
Hemiplegic Migraine, Familial Type 1 53 73
Fhm 57 75
Migraine, Familial Hemiplegic, 1, with Progressive Cerebellar Ataxia 57
Migraine, Familial Hemiplegic 1, with Progressive Cerebellar Ataxia 53
Migraine Familial Hemiplegic with Progressive Cerebellar Ataxia 75
Migraine, Hemiplegic, Familial, Type 1 40

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity
subtype of migraine with aura
onset 5-30 years
symptoms usually last 30-60 minutes
pulsatile headache lasts hours to days
in severe attacks, hemiplegia or coma may last days to weeks
triggered by minor head trauma
marked clinical variability within families
allelic disorder to episodic ataxia-2 (ea2, ) and spinocerebellar ataxia-6 (sca6, )


HPO:

32
migraine, familial hemiplegic, 1:
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Migraine, Familial Hemiplegic, 1

NIH Rare Diseases : 53 Familial hemiplegic migraine (FHM) is a form of migraine headache that runs in families. Migraines usually cause intense, throbbing pain in one area of the head, often accompanied by nausea, vomiting, and extreme sensitivity to light and sound. These recurrent headaches typically begin in childhood or adolescence and may last from a few hours to a few days. People with familial hemiplegic migraine experience an aura that comes before the headache. The most common symptoms associated with an aura are temporary visual changes such as blind spots (scotomas), flashing lights, zig-zagging lines, and double vision. In people with familial hemiplegic migraine, auras are also characterized by temporary numbness or weakness, often affecting one side of the body (hemiparesis). An aura typically develops gradually over a few minutes and lasts about an hour. Researchers have identified three forms of familial hemiplegic migraine known as FHM1, FHM2, and FHM3. Each of the three types is caused by mutations in a different gene. Treatment varies depending on signs and symptoms and may include use of anti migraine or anti seizure medications.

MalaCards based summary : Migraine, Familial Hemiplegic, 1, also known as familial hemiplegic migraine type 1, is related to familial hemiplegic migraine and alternating hemiplegia of childhood 1, and has symptoms including cerebellar ataxia, fever and hemiparesis. An important gene associated with Migraine, Familial Hemiplegic, 1 is CACNA1A (Calcium Voltage-Gated Channel Subunit Alpha1 A). The drugs Nitroglycerin and Salmon Calcitonin have been mentioned in the context of this disorder. Affiliated tissues include brain, bone and trigeminal ganglion, and related phenotypes are nystagmus and psychosis

UniProtKB/Swiss-Prot : 75 Migraine, familial hemiplegic, 1: A subtype of migraine with aura associated with ictal hemiparesis and, in some families, cerebellar ataxia and atrophy. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. Migraine with aura is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking.

Description from OMIM: 141500

Related Diseases for Migraine, Familial Hemiplegic, 1

Diseases in the Hemiplegic Migraine family:

Migraine, Familial Hemiplegic, 1 Migraine, Familial Hemiplegic, 2
Migraine, Familial Hemiplegic, 3 Familial Hemiplegic Migraine
Sporadic Hemiplegic Migraine Familial or Sporadic Hemiplegic Migraine

Diseases related to Migraine, Familial Hemiplegic, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 familial hemiplegic migraine 11.4
2 alternating hemiplegia of childhood 1 10.9
3 migraine with or without aura 1 10.9
4 migraine, familial hemiplegic, 2 10.9
5 migraine, familial hemiplegic, 3 10.9
6 hemiplegic migraine 9.9

Graphical network of the top 20 diseases related to Migraine, Familial Hemiplegic, 1:



Diseases related to Migraine, Familial Hemiplegic, 1

Symptoms & Phenotypes for Migraine, Familial Hemiplegic, 1

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
dysphasia
migraine
hemiplegia
confusion
hemiparesis
more
Neurologic Behavioral Psychiatric Manifestations:
visual hallucinations
auditory hallucinations
anxiety attacks
paranoid psychosis

Metabolic Features:
fever

Head And Neck Eyes:
hemianopic blurring of vision
nystagmus (may be permanent in 50% of patients)


Clinical features from OMIM:

141500

Human phenotypes related to Migraine, Familial Hemiplegic, 1:

32 (show all 21)
# Description HPO Frequency HPO Source Accession
1 nystagmus 32 HP:0000639
2 psychosis 32 HP:0000709
3 agitation 32 HP:0000713
4 anxiety 32 HP:0000739
5 transient unilateral blurring of vision 32 HP:0001125
6 seizures 32 occasional (7.5%) HP:0001250
7 ataxia 32 HP:0001251
8 coma 32 HP:0001259
9 hemiparesis 32 HP:0001269
10 cerebellar atrophy 32 HP:0001272
11 confusion 32 HP:0001289
12 tremor 32 occasional (7.5%) HP:0001337
13 fever 32 HP:0001945
14 migraine 32 HP:0002076
15 migraine with aura 32 HP:0002077
16 hemiplegia 32 HP:0002301
17 drowsiness 32 HP:0002329
18 dysphasia 32 HP:0002357
19 visual hallucinations 32 HP:0002367
20 dyscalculia 32 HP:0002442
21 auditory hallucinations 32 HP:0008765

UMLS symptoms related to Migraine, Familial Hemiplegic, 1:


cerebellar ataxia, fever, hemiparesis, hemiplegia, hallucinations, auditory, hallucinations, visual

Drugs & Therapeutics for Migraine, Familial Hemiplegic, 1

Drugs for Migraine, Familial Hemiplegic, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Nitroglycerin Approved, Investigational Not Applicable 55-63-0 4510
2
Salmon Calcitonin Approved, Investigational Not Applicable 47931-85-1 16129616
3
Calcitonin gene-related peptide Investigational Not Applicable 83652-28-2
4 calcitonin Not Applicable
5 Vasodilator Agents Not Applicable
6 Bone Density Conservation Agents Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Glyceryl-Trinitrate-Induced Headache in Patients With Familial Hemiplegic Migraine Type 1 and 2 Completed NCT00257985 Not Applicable GTN
2 Calcitonin Gene Related Peptide-Induced Headache in Patients With Familial Hemiplegic Migraine Type 1 and 2. Completed NCT00358839 Not Applicable CGRP

Search NIH Clinical Center for Migraine, Familial Hemiplegic, 1

Genetic Tests for Migraine, Familial Hemiplegic, 1

Genetic tests related to Migraine, Familial Hemiplegic, 1:

# Genetic test Affiliating Genes
1 Familial Hemiplegic Migraine Type 1 29 CACNA1A

Anatomical Context for Migraine, Familial Hemiplegic, 1

MalaCards organs/tissues related to Migraine, Familial Hemiplegic, 1:

41
Brain, Bone, Trigeminal Ganglion, Cerebellum

Publications for Migraine, Familial Hemiplegic, 1

Articles related to Migraine, Familial Hemiplegic, 1:

(show all 24)
# Title Authors Year
1
Ten years of follow-up in a large family with familial hemiplegic migraine type 1: Clinical course and implications for treatment. ( 28856914 )
2017
2
Cerebellar Atrophy and Changes in Cytokines Associated with the CACNA1A R583Q Mutation in a Russian Familial Hemiplegic Migraine Type 1 Family. ( 28900389 )
2017
3
Activity-dependent calcium, oxygen, and vascular responses in a mouse model of familial hemiplegic migraine type 1. ( 27314908 )
2016
4
Time course of downbeat positioning nystagmus in familial hemiplegic migraine type 1 treated with acetazolamide. ( 27538634 )
2016
5
Abnormal synaptic Ca(2+) homeostasis and morphology in cortical neurons of familial hemiplegic migraine type 1 mutant mice. ( 26032020 )
2015
6
Familial hemiplegic migraine type 1 associated with parkinsonism: a case report. ( 25969684 )
2015
7
Stress hormone corticosterone enhances susceptibility to cortical spreading depression in familial hemiplegic migraine type 1 mutant mice. ( 25447936 )
2015
8
Repeated encephalopathy and hemicerebral atrophy in a patient with familial hemiplegic migraine type 1. ( 25274239 )
2014
9
An altered GABA-A receptor function in spinocerebellar ataxia type 6 and familial hemiplegic migraine type 1 associated with the CACNA1A gene mutation. ( 26675662 )
2014
10
The familial hemiplegic migraine type 1 mutation K1336E affects direct G protein-mediated regulation of neuronal P/Q-type Ca2+ channels. ( 23430985 )
2013
11
The mechanism of functional up-regulation of P2X3 receptors of trigeminal sensory neurons in a genetic mouse model of familial hemiplegic migraine type 1 (FHM-1). ( 23577145 )
2013
12
RNA expression profiling in brains of familial hemiplegic migraine type 1 knock-in mice. ( 23985897 )
2013
13
Effects of familial hemiplegic migraine type 1 mutation T666M on voltage-gated calcium channel activities in trigeminal ganglion neurons. ( 22190617 )
2012
14
Familial hemiplegic migraine type 1 mutations W1684R and V1696I alter G protein-mediated regulation of Ca(V)2.1 voltage-gated calcium channels. ( 22549042 )
2012
15
Enhanced subcortical spreading depression in familial hemiplegic migraine type 1 mutant mice. ( 21490217 )
2011
16
Severe and progressive neurotransmitter release aberrations in familial hemiplegic migraine type 1 Cacna1a S218L knock-in mice. ( 20631222 )
2010
17
Androgenic suppression of spreading depression in familial hemiplegic migraine type 1 mutant mice. ( 19847904 )
2009
18
Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1. ( 19104150 )
2009
19
Expansion of the phenotypic spectrum of the CACNA1A T666M mutation: a family with familial hemiplegic migraine type 1, cerebellar atrophy and mental retardation. ( 18279427 )
2008
20
Familial hemiplegic migraine type 1 shows no hypersensitivity to nitric oxide. ( 18384418 )
2008
21
1H-MRS alterations in the cerebellum of patients with familial hemiplegic migraine type 1. ( 15728280 )
2005
22
Effects of familial hemiplegic migraine type 1 mutations on neuronal P/Q-type Ca2+ channel activity and inhibitory synaptic transmission. ( 15699344 )
2005
23
Gating deficiency in a familial hemiplegic migraine type 1 mutant P/Q-type calcium channel. ( 15795222 )
2005
24
Familial hemiplegic migraine type 1 mutations K1336E, W1684R, and V1696I alter Cav2.1 Ca2+ channel gating: evidence for beta-subunit isoform-specific effects. ( 15448138 )
2004

Variations for Migraine, Familial Hemiplegic, 1

UniProtKB/Swiss-Prot genetic disease variations for Migraine, Familial Hemiplegic, 1:

75 (show all 15)
# Symbol AA change Variation ID SNP ID
1 CACNA1A p.Arg192Gln VAR_001491 rs121908211
2 CACNA1A p.Thr666Met VAR_001492 rs121908212
3 CACNA1A p.Val714Ala VAR_001493 rs121908213
4 CACNA1A p.Ile1810Leu VAR_001494 rs121908214
5 CACNA1A p.Arg195Lys VAR_043820 rs121908222
6 CACNA1A p.Ser218Leu VAR_043821 rs121908225
7 CACNA1A p.Arg583Gln VAR_043826 rs121908217
8 CACNA1A p.Asp715Glu VAR_043827 rs121908218
9 CACNA1A p.Lys1335Glu VAR_043829 rs121908223
10 CACNA1A p.Arg1346Gln VAR_043830 rs121908230
11 CACNA1A p.Tyr1384Cys VAR_043831 rs121908219
12 CACNA1A p.Val1456Leu VAR_043833 rs121908237
13 CACNA1A p.Arg1667Trp VAR_043838 rs121908220
14 CACNA1A p.Trp1683Arg VAR_043839 rs121908221
15 CACNA1A p.Val1695Ile VAR_063706 rs121908224

ClinVar genetic disease variations for Migraine, Familial Hemiplegic, 1:

6
(show all 34)
# Gene Variation Type Significance SNP ID Assembly Location
1 CACNA1A NM_001127221.1(CACNA1A): c.575G> A (p.Arg192Gln) single nucleotide variant Pathogenic rs121908211 GRCh37 Chromosome 19, 13482558: 13482558
2 CACNA1A NM_001127221.1(CACNA1A): c.575G> A (p.Arg192Gln) single nucleotide variant Pathogenic rs121908211 GRCh38 Chromosome 19, 13371744: 13371744
3 CACNA1A NM_001127221.1(CACNA1A): c.1997C> T (p.Thr666Met) single nucleotide variant Pathogenic rs121908212 GRCh37 Chromosome 19, 13414691: 13414691
4 CACNA1A NM_001127221.1(CACNA1A): c.1997C> T (p.Thr666Met) single nucleotide variant Pathogenic rs121908212 GRCh38 Chromosome 19, 13303877: 13303877
5 CACNA1A NM_001127221.1(CACNA1A): c.2141T> C (p.Val714Ala) single nucleotide variant Pathogenic rs121908213 GRCh37 Chromosome 19, 13414394: 13414394
6 CACNA1A NM_001127221.1(CACNA1A): c.2141T> C (p.Val714Ala) single nucleotide variant Pathogenic rs121908213 GRCh38 Chromosome 19, 13303580: 13303580
7 CACNA1A NM_001127221.1(CACNA1A): c.5428A> C (p.Ile1810Leu) single nucleotide variant Pathogenic rs121908214 GRCh37 Chromosome 19, 13340999: 13340999
8 CACNA1A NM_001127221.1(CACNA1A): c.5428A> C (p.Ile1810Leu) single nucleotide variant Pathogenic rs121908214 GRCh38 Chromosome 19, 13230185: 13230185
9 CACNA1A NM_001127221.1(CACNA1A): c.2145C> A (p.Asp715Glu) single nucleotide variant Pathogenic rs121908218 GRCh37 Chromosome 19, 13414390: 13414390
10 CACNA1A NM_001127221.1(CACNA1A): c.2145C> A (p.Asp715Glu) single nucleotide variant Pathogenic rs121908218 GRCh38 Chromosome 19, 13303576: 13303576
11 CACNA1A NM_001127221.1(CACNA1A): c.4151A> G (p.Tyr1384Cys) single nucleotide variant Pathogenic rs121908219 GRCh37 Chromosome 19, 13372366: 13372366
12 CACNA1A NM_001127221.1(CACNA1A): c.4151A> G (p.Tyr1384Cys) single nucleotide variant Pathogenic rs121908219 GRCh38 Chromosome 19, 13261552: 13261552
13 CACNA1A NM_001127221.1(CACNA1A): c.4366G> T (p.Val1456Leu) single nucleotide variant Pathogenic rs121908237 GRCh37 Chromosome 19, 13370403: 13370403
14 CACNA1A NM_001127221.1(CACNA1A): c.4366G> T (p.Val1456Leu) single nucleotide variant Pathogenic rs121908237 GRCh38 Chromosome 19, 13259589: 13259589
15 CACNA1A NM_001127221.1(CACNA1A): c.653C> T (p.Ser218Leu) single nucleotide variant Pathogenic rs121908225 GRCh37 Chromosome 19, 13476262: 13476262
16 CACNA1A NM_001127221.1(CACNA1A): c.653C> T (p.Ser218Leu) single nucleotide variant Pathogenic rs121908225 GRCh38 Chromosome 19, 13365448: 13365448
17 CACNA1A NM_001127221.1(CACNA1A): c.1748G> A (p.Arg583Gln) single nucleotide variant Pathogenic rs121908217 GRCh37 Chromosome 19, 13419266: 13419266
18 CACNA1A NM_001127221.1(CACNA1A): c.1748G> A (p.Arg583Gln) single nucleotide variant Pathogenic rs121908217 GRCh38 Chromosome 19, 13308452: 13308452
19 CACNA1A NM_001127221.1(CACNA1A): c.5126T> C (p.Ile1709Thr) single nucleotide variant Pathogenic rs121909326 GRCh37 Chromosome 19, 13346033: 13346033
20 CACNA1A NM_001127221.1(CACNA1A): c.5126T> C (p.Ile1709Thr) single nucleotide variant Pathogenic rs121909326 GRCh38 Chromosome 19, 13235219: 13235219
21 CACNA1A NM_001127221.1(CACNA1A): c.4037G> A (p.Arg1346Gln) single nucleotide variant Pathogenic rs121908230 GRCh37 Chromosome 19, 13373603: 13373603
22 CACNA1A NM_001127221.1(CACNA1A): c.4037G> A (p.Arg1346Gln) single nucleotide variant Pathogenic rs121908230 GRCh38 Chromosome 19, 13262789: 13262789
23 CACNA1A NG_011569.1: g.(286795_296853)_(303563_305019)del deletion Pathogenic GRCh38 Chromosome 19, 13206442: 13224666
24 CACNA1A NG_011569.1: g.(286795_296853)_(303563_305019)del deletion Pathogenic GRCh37 Chromosome 19, 13317256: 13335480
25 CACNA1A NG_011569.1: g.(286795_296853)_(303563_305019)del deletion Pathogenic GRCh38 Chromosome 19, 13206442: 13224666
26 CACNA1A NG_011569.1: g.(286795_296853)_(303563_305019)del deletion Pathogenic GRCh37 Chromosome 19, 13317256: 13335480
27 CACNA1A NM_001127221.1(CACNA1A): c.4999C> T (p.Arg1667Trp) single nucleotide variant Pathogenic rs121908220 GRCh37 Chromosome 19, 13346499: 13346499
28 CACNA1A NM_001127221.1(CACNA1A): c.4999C> T (p.Arg1667Trp) single nucleotide variant Pathogenic rs121908220 GRCh38 Chromosome 19, 13235685: 13235685
29 CACNA1A NM_001127221.1(CACNA1A): c.4177G> A (p.Val1393Met) single nucleotide variant Conflicting interpretations of pathogenicity rs794727411 GRCh37 Chromosome 19, 13372340: 13372340
30 CACNA1A NM_001127221.1(CACNA1A): c.4177G> A (p.Val1393Met) single nucleotide variant Conflicting interpretations of pathogenicity rs794727411 GRCh38 Chromosome 19, 13261526: 13261526
31 CACNA1A NM_001127222.1(CACNA1A): c.1345+7C> T single nucleotide variant Benign/Likely benign rs192536793 GRCh38 Chromosome 19, 13330237: 13330237
32 CACNA1A NM_001127222.1(CACNA1A): c.1345+7C> T single nucleotide variant Benign/Likely benign rs192536793 GRCh37 Chromosome 19, 13441051: 13441051
33 CACNA1A NM_001127221.1(CACNA1A): c.1060C> T (p.Leu354Phe) single nucleotide variant Conflicting interpretations of pathogenicity GRCh37 Chromosome 19, 13446642: 13446642
34 CACNA1A NM_001127221.1(CACNA1A): c.1060C> T (p.Leu354Phe) single nucleotide variant Conflicting interpretations of pathogenicity GRCh38 Chromosome 19, 13335828: 13335828

Expression for Migraine, Familial Hemiplegic, 1

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