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Migraine, familial hemiplegic, 1(FHM1)

MedGen UID:
331388
Concept ID:
C1832884
Disease or Syndrome
Synonym: Migraine, familial hemiplegic 1, with progressive cerebellar ataxia
 
Gene (location): CACNA1A (19p13.13)
 
Monarch Initiative: MONDO:0020756
OMIM®: 141500

Disease characteristics

Excerpted from the GeneReview: Familial Hemiplegic Migraine
Familial hemiplegic migraine (FHM) falls within the category of migraine with aura. In migraine with aura (including FHM) the neurologic symptoms of aura are unequivocally localizable to the cerebral cortex or brain stem and include visual disturbance (most common), sensory loss (e.g., numbness or paresthesias of the face or an extremity), and dysphasia (difficulty with speech). FHM must include motor involvement, such as hemiparesis (weakness of an extremity). Hemiparesis occurs with at least one other symptom during FHM aura. Neurologic deficits with FHM attacks can be prolonged for hours to days and may outlast the associated migrainous headache. FHM is often earlier in onset than typical migraine, frequently beginning in the first or second decade; the frequency of attacks tends to decrease with age. Approximately 40%-50% of families with CACNA1A-FHM have cerebellar signs ranging from nystagmus to progressive, usually late-onset mild ataxia. [from GeneReviews]
Authors:
Joanna C Jen   view full author information

Additional description

From OMIM
Familial hemiplegic migraine-1 (FHM1) is an autosomal dominant form of migraine with aura. Typical attacks include a unilateral motor deficit associated with paresthesias, speech disturbances, or visual signs. These aura symptoms last from 10 minutes to a few hours and are followed by a migrainous headache. In some families, affected individuals have permanent cerebellar symptoms, such as nystagmus and slowly progressive mild to moderate statokinetic ataxia. In some cases, cerebral magnetic resonance imaging (MRI) reveals cerebellar atrophy (summary by Ducros et al., 1999). Genetic Heterogeneity of Familial Hemiplegic Migraine See also FHM2 (602481), caused by mutation in the ATP1A2 gene (182340); FHM3 (609634), caused by mutation in the SCN1A gene (182389); and FHM4 (see 607516), mapped to chromosome 1q31.  http://www.omim.org/entry/141500

Clinical features

From HPO
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tenseness, or panic, often in reaction to interpersonal stresses; worry about the negative effects of past unpleasant experiences and future negative possibilities; feeling fearful, apprehensive, or threatened by uncertainty; fears of falling apart or losing control.
Aphasia
MedGen UID:
8159
Concept ID:
C0003537
Mental or Behavioral Dysfunction
An acquired language impairment of some or all of the abilities to produce or comprehend speech and to read or write.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Coma
MedGen UID:
1054
Concept ID:
C0009421
Disease or Syndrome
Complete absence of wakefulness and content of conscience, which manifests itself as a lack of response to any kind of external stimuli.
Confusion
MedGen UID:
3587
Concept ID:
C0009676
Mental or Behavioral Dysfunction
Lack of clarity and coherence of thought, perception, understanding, or action.
Drowsiness
MedGen UID:
4390
Concept ID:
C0013144
Finding
Excessive daytime sleepiness.
Hemiparesis
MedGen UID:
6783
Concept ID:
C0018989
Finding
Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a complete loss of strength, whereas hemiparesis refers to an incomplete loss of strength.
Hemiplegia
MedGen UID:
9196
Concept ID:
C0018991
Sign or Symptom
Paralysis (complete loss of muscle function) in the arm, leg, and in some cases the face on one side of the body.
Psychosis
MedGen UID:
19568
Concept ID:
C0033975
Mental or Behavioral Dysfunction
A condition characterized by changes of personality and thought patterns often accompanied by hallucinations and delusional beliefs.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Agitation
MedGen UID:
88447
Concept ID:
C0085631
Sign or Symptom
A state of exceeding restlessness and excessive motor activity associated with mental distress or a feeling of inner tension.
Migraine
MedGen UID:
57451
Concept ID:
C0149931
Disease or Syndrome
Migraine is the most common type of chronic, episodic headache, as summarized by Featherstone (1985). One locus for migraine with or without aura (MGR1) has been identified on chromosome 4q24. Other loci for migraine have been identified on 6p21.1-p12.2 (MGR3; 607498), 14q21.2-q22.3 (MGR4; 607501), 19p13 (MGR5; 607508), 1q31 (MGR6; 607516), 15q11-q13 (MGR7; 609179), 5q21 (with or without aura, MGR8, 609570; with aura, MGR9, 609670), 17p13 (MGR10; 610208), 18q12 (MGR11; 610209), 10q22-q23 (MGR12; 611706), and the X chromosome (MGR2; 300125). Mutation in the KCNK18 gene (613655) on chromosome 10q25 causes migraine with aura (MGR13; 613656). A subtype of autosomal dominant migraine with aura (MA), familial hemiplegic migraine (FHM; see 141500), is caused by mutation in the CACNA1A gene (601011) on chromosome 19p13 (FHM1; 141500), by mutation in the ATP1A2 gene (182340) on chromosome 1q21 (FHM2; 602481), or by mutation in the SCN1A gene (182389) on chromosome 2q24 (FHM3; 609634). Another locus for FHM has been mapped to chromosome 1q31 (FHM4; see 607516). There is evidence that a polymorphism in the estrogen receptor gene (ESR1; 133430.0005) and a polymorphism in the TNF gene (191160.0004) may confer susceptibility to migraine. A polymorphism in the endothelin receptor type A gene (EDNRA; 131243.0001) may confer resistance to migraine.
Migraine with aura
MedGen UID:
57822
Concept ID:
C0154723
Disease or Syndrome
A type of migraine in which there is an aura characterized by focal neurological phenomena that usually proceed, but may accompany or occur in the absence of, the headache. The symptoms of an aura may include fully reversible visual, sensory, and speech symptoms but not motor weakness. Visual symptoms may include flickering lights, spots and lines and/or loss of vision and/or unilateral sensory symptoms such as paresthesias or numbness. At least one of the symptoms of an aura develops gradually over 5 or more minutes and/or different symptoms occur in succession.
Auditory hallucinations
MedGen UID:
115932
Concept ID:
C0233762
Sign or Symptom
The false perception of sound.
Visual hallucinations
MedGen UID:
66688
Concept ID:
C0233763
Sign or Symptom
Visual perceptions that are not elicited by a corresponding stimulus from the outside world.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Dyscalculia
MedGen UID:
452779
Concept ID:
C0869474
Mental or Behavioral Dysfunction
A specific learning disability involving mathematics and arithmetic.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Transient unilateral blurring of vision
MedGen UID:
356249
Concept ID:
C1865332
Finding
Transient blurring of vision associated with the aura phase of migraine.

Recent clinical studies

Etiology

Indelicato E, Nachbauer W, Karner E, Eigentler A, Wagner M, Unterberger I, Poewe W, Delazer M, Boesch S
Eur J Neurol 2019 Jan;26(1):66-e7. Epub 2018 Sep 3 doi: 10.1111/ene.13765. PMID: 30063100
Ambrosini A, D'Onofrio M, Buzzi MG, Arisi I, Grieco GS, Pierelli F, Santorelli FM, Schoenen J
Headache 2017 Jul;57(7):1136-1144. Epub 2017 Jun 1 doi: 10.1111/head.13107. PMID: 28573794

Diagnosis

Luan H, Zhang L, Zhang S, Zhang M
Medicine (Baltimore) 2021 Dec 23;100(51):e28141. doi: 10.1097/MD.0000000000028141. PMID: 34941060Free PMC Article
Sprouse Blum AS, Couperus CJ, Rosen BJ, Haskin-Leahy LF, Shapiro RE
Headache 2020 Mar;60(3):600-606. Epub 2020 Jan 22 doi: 10.1111/head.13741. PMID: 31967333
Indelicato E, Nachbauer W, Karner E, Eigentler A, Wagner M, Unterberger I, Poewe W, Delazer M, Boesch S
Eur J Neurol 2019 Jan;26(1):66-e7. Epub 2018 Sep 3 doi: 10.1111/ene.13765. PMID: 30063100
Tashiro Y, Yamazaki T, Nagamine S, Mizuno Y, Yoshiki A, Okamoto K
Intern Med 2014;53(19):2245-50. doi: 10.2169/internalmedicine.53.0295. PMID: 25274239

Therapy

Luan H, Zhang L, Zhang S, Zhang M
Medicine (Baltimore) 2021 Dec 23;100(51):e28141. doi: 10.1097/MD.0000000000028141. PMID: 34941060Free PMC Article
Magni G, Boccazzi M, Bodini A, Abbracchio MP, van den Maagdenberg AM, Ceruti S
Cephalalgia 2019 Dec;39(14):1809-1817. Epub 2019 Jul 1 doi: 10.1177/0333102419861710. PMID: 31260335
García Segarra N, Gautschi I, Mittaz-Crettol L, Kallay Zetchi C, Al-Qusairi L, Van Bemmelen MX, Maeder P, Bonafé L, Schild L, Roulet-Perez E
J Neurol Sci 2014 Jul 15;342(1-2):69-78. Epub 2014 Apr 27 doi: 10.1016/j.jns.2014.04.027. PMID: 24836863

Prognosis

Luan H, Zhang L, Zhang S, Zhang M
Medicine (Baltimore) 2021 Dec 23;100(51):e28141. doi: 10.1097/MD.0000000000028141. PMID: 34941060Free PMC Article

Clinical prediction guides

Luan H, Zhang L, Zhang S, Zhang M
Medicine (Baltimore) 2021 Dec 23;100(51):e28141. doi: 10.1097/MD.0000000000028141. PMID: 34941060Free PMC Article
García Segarra N, Gautschi I, Mittaz-Crettol L, Kallay Zetchi C, Al-Qusairi L, Van Bemmelen MX, Maeder P, Bonafé L, Schild L, Roulet-Perez E
J Neurol Sci 2014 Jul 15;342(1-2):69-78. Epub 2014 Apr 27 doi: 10.1016/j.jns.2014.04.027. PMID: 24836863

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    Curated

    • NICE, 2021
      UK NICE Guideline CG150, Headaches in over 12s: diagnosis and management, 2021
    • Orphanet, 2013
      Orphanet, Hemiplegic Migraine (HM), 2013

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