Disease Profile

Familiar or sporadic hemiplegic migraine

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of Onset

Childhood

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ICD-10

G43.1

Inheritance

Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Familial or sporadic hemiplegic migraine refers to a rare type of migraine with aura that occurs with motor weakness during the aura. The two types of hemiplegic migraine (HM) are distinguished based on the family historyfamilial hemiplegic migraine (FHM, in which at least one other family member has the condition) and sporadic hemiplegic migraine (SHM, in which there is no family history).[1] Signs and symptoms vary but may include visual disturbances, sensory loss, difficulty with speech, weakness on one side of the body, confusion, and impaired consciousness.[2] Severe attacks may occur in both types with prolonged hemiplegia, coma, fever and/or seizures.[1] FHM may be caused by a mutation in any of several genes and is inherited in an autosomal dominant manner.[1][2]

Symptoms

The symptoms and severity can vary considerably among people with hemiplegic migraine. Signs and symptoms associated with aura may include:[3]

  • Visual disturbance (e.g. blind spots, flashing lights, zigzag pattern, and double vision)
  • Sensory loss (e.g., numbness or paresthesias of the face or an extremity)
  • Difficulty with speech (which usually occur along with right-sided weakness)

Motor weakness involves areas affected by sensory symptoms and varies from mild clumsiness to complete deficit. Affected people may also experience neurologic symptoms such as confusion, drowsiness, impaired consciousness, coma, psychosis, and/or memory loss. Neurologic symptoms can last for hours to days. Attention and memory loss can last weeks to months. However, permanent motor, sensory, language, or visual symptoms are extremely rare.[3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Focal motor seizure
0011153
Focal sensory seizure
0011157
30%-79% of people have these symptoms
Cerebral edema
Swelling of brain
0002181
Complex febrile seizure
0011172
Confusion
Disorientation
Easily confused
Mental disorientation

[ more ]

0001289
CSF lymphocytic pleiocytosis
0200149
Diplopia
Double vision
0000651
Dissociated sensory loss
0010835
Dysarthria
Difficulty articulating speech
0001260
Facial tics
Cramping of facial muscles
Facial spasms
Jerking of facial muscles
Mimic spasms
Spasms of facial muscles
Twitching of facial muscles

[ more ]

0011468
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Increased CSF protein
0002922
Metamorphopsia
0012508
Paresthesia
Pins and needles feeling
Tingling

[ more ]

0003401
Photopsia
0030786
Postural instability
Balance impairment
0002172
Progressive gait ataxia
0007240
Scotoma
0000575
Tongue fasciculations
Tongue twitching
Twitching of the tongue

[ more ]

0001308
Vertigo
Dizzy spell
0002321
5%-29% of people have these symptoms
Alien limb phenomenon
0032506
Cerebellar atrophy
Degeneration of cerebellum
0001272
Coma
0001259
Decreased vigilance
0032044
Distal upper limb muscle weakness
0008959
Dysphasia
0002357
EEG with generalized sharp slow waves
0011199
Facial paralysis
0007209
Gaze-evoked horizontal nystagmus
0007979
Impaired thermal sensitivity
0006901
Nuchal rigidity
0031179
Seesaw nystagmus
0012044
Spontaneous pain sensation
0010833
Tinnitus
Ringing in ears
Ringing in the ears

[ more ]

0000360
Tremor
0001337
Vertical nystagmus
0010544
1%-4% of people have these symptoms
Amaurosis fugax
0100576
EEG with focal sharp waves
0011196
First dorsal interossei muscle weakness
0003392
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Status epilepticus
Repeated seizures without recovery between them
0002133
Percent of people who have these symptoms is not available through HPO
Agitation
0000713
Anxiety
Excessive, persistent worry and fear
0000739
Aphasia
Difficulty finding words
Losing words
Loss of words

[ more ]

0002381
Apraxia
0002186
Ataxia
0001251
Auditory hallucinations
Hallucinations of sound
Hearing sounds

[ more ]

0008765
Autosomal dominant inheritance
0000006
Blindness
0000618
Blurred vision
0000622
Drowsiness
Sleepy
0002329
Dyscalculia
0002442
Episodic ataxia
0002131
Fever
0001945
Hemiparesis
Weakness of one side of body
0001269
Hemiplegia
Paralysis on one side of body
0002301
Incomplete penetrance
0003829
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches

[ more ]

0002076
Migraine with aura
0002077
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Photophobia
Extreme sensitivity of the eyes to light
Light hypersensitivity

[ more ]

0000613
Psychosis
0000709
Seizure

Cause

There are two types of hemiplegic migraine (HM), which are distinguished based on the family history in affected people: familial hemiplegic migraine (FHM, in which at least one other close family member has the condition) and sporadic hemiplegic migraine (SHM, in which there is no family history).[1]

FHM may be caused by changes (mutations) in the CACNA1A, ATP1A2, SCN1A, and PRRT2 genes. The first three of these genes give the body instructions for making proteins involved in moving charged atoms (ions) across cell membranes. This process is important for for normal signaling between nerve cells (neurons) in the brain and other parts of the nervous system. Researchers think that mutations in these genes may upset the balance of ions in neurons, affecting the release and uptake of certain neurotransmitters in the brain. The exact function of the PRRT2 gene is not yet understood but is also thought to play a part in controlling signals between neurons. When the genes involved in FHM do not work correctly, the signaling abnormalities between neurons lead to the development of severe headaches and auras in affected people.[4] The genetic cause in many families with FHM remains unknown.[3]

While SHM occurs in people with no history of the condition in their family, most cases are due to new (de novo) mutations that occur for the first time in the affected person. Some people with SHM do inherit a mutation from a parent who has the mutation but is not affected. The ATP1A2 and CACNA1A genes have been found to cause SHM in addition to FHM. Many people with SHM do not have a mutation in one of these genes; however, researchers think that mutations in other, unidentified genes are also involved in the condition.[5]

Diagnosis

Hemiplegic migraine is diagnosed based on the presence of specific signs and symptoms. Genetic testing is not necessary for all affected people.[6]

The diagnosis is based on the presence of having at least 2 attacks with:

  • aura accompanied by fully reversible motor weakness and fully reversible visual, sensory, and/or speech/language symptoms; and
  • at least 2 of the following 4 characteristics:
    • at least one aura symptom that spreads gradually over ≥5 minutes, and/or two or more symptoms that occur in succession
    • each individual non-motor aura symptom lasting 5 to 60 minutes, and motor symptoms lasting <72 hours
    • at least one unilateral (one-sided) aura symptom
    • the aura being accompanied by headache, or followed by headache within one hour[6]

Additionally, all other potential causes for the symptoms need to be ruled out (such as transient ischemic attack and stroke). While the criteria requires fully reversible symptoms, it is known that some people with severe attacks may have permanent neurological problems.[6]

A diagnosis of familial hemiplegic migraine also requires that at least one first or second degree relative has had attacks that meet the above diagnostic criteria. A diagnosis of sporadic hemiplegic migraine requires that no first or second degree relative has had attacks that meet the above criteria.[6]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment of hemiplegic migraine varies depending on severity and which symptoms are most problematic for the patient. In general, treatments aim to manage symptoms. Drugs that are effective in the prevention of common migraines may be used in hemiplegic migraine.[3] Prophylactic management is applied to patients with frequent, long lasting, or severe attacks. Examples of migraine drugs that have been tried with variable success in people with hemiplegic migraine, include oral verapamil, acetazolamide, lamotrigine.[3]

    There are a few articles describing the use of nasal administration of ketamine, intravenous verapamil, and triptans for treatment of aura in people with hemiplegic migraine. Use of triptans in hemiplegic migraine is controversial and may be contraindicated in people with severe attacks.[3]

    For further information on these and other treatments, we recommend that you speak with your healthcare provider.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

        Learn More

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

          In-Depth Information

          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            Familial hemiplegic migraine 1
            Familial hemiplegic migraine 2
            Familial hemiplegic migraine 3
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Familiar or sporadic hemiplegic migraine. Click on the link to view a sample search on this topic.

            References

            1. Anne Ducros. Familial or sporadic hemiplegic migraine. Orphanet. April, 2008; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=569. Accessed 11/17/2014.
            2. Russell MB, Ducros A. Sporadic and familial hemiplegic migraine: pathophysiological mechanisms, clinical characteristics, diagnosis, and management. Lancet Neurol. May, 2011; https://www.ncbi.nlm.nih.gov/pubmed/21458376. Accessed 8/26/2013.
            3. Jen JC. Familial Hemiplegic Migraine. GeneReviews. September 2009; https://www.ncbi.nlm.nih.gov/books/NBK1388/#fhm.Clinical_Description.
            4. Familial hemiplegic migraine. Genetics Home Reference. January, 2014; https://ghr.nlm.nih.gov/condition/familial-hemiplegic-migraine. Accessed 12/5/2016.
            5. Sporadic hemiplegic migraine. Genetics Home Reference. February, 2014; https://ghr.nlm.nih.gov/condition/sporadic-hemiplegic-migraine. Accessed 11/18/2014.
            6. Black DF, Robertson CE. Hemiplegic migraine. In: Swanson JW ed.,. UpToDate. Waltham, MA: UpToDate; 2015; https://www.uptodate.com/contents/hemiplegic-migraine.