Rare Pulmonology News

Disease Profile

Familial 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.

Unknown

Age of onset

#N/A

ICD-10

#N/A

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.

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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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Other names (AKA)

FHM; Hemiplegic Migraine, Familial; Hemiplegic-ophthalmoplegic migraine

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Familial hemiplegic migraine (FHM) is an inherited form of hemiplegic migraine. Hemiplegic migraine is a type of migraine with aura that causes motor impairment (such as weakness) in addition to at least one visual, sensory, or speech disturbance (aura) that occurs before the migraine headache begins.[1][2] FHM commonly begins during childhood or adolescence.[2] The symptoms of FHM can be scary and distressing.[1]

FHM is currently classified into 4 subtypes, distinguished by their genetic cause:[1][2]

  • FHM type 1 (the most common type) is caused by mutations in the CACNA1A gene and is commonly associated with cerebellar degeneration.
  • FHM type 2 is caused by mutations in the ATP1A2 gene and may be associated with seizures.
  • FHM type 3 is caused by mutations in the SCN1A gene.
  • FHM type 4 is diagnosed if no mutation currently known to cause FHM can be identified.

Inheritance of FHM is autosomal dominant, but not everyone who inherits a mutation responsible for FHM will have symptoms (a phenomenon called reduced penetrance).[1][3] The diagnosis of FHM requires that at least one firstor second-degree relative has also been diagnosed with hemiplegic migraine. Tests such as a CT scan or MRI of the brain, cerebrospinal fluid analysis, and EEG may be needed to rule out other potential causes of headache and neurological symptoms.[1] Genetic testing may confirm the subtype of FHM in a family. Treatment of hemiplegic migraine involves medications to alleviate pain, stop the migraines, and prevent future migraines. Severe headache attacks may require hospitalization.[1] In most people with hemiplegic migraines, aura symptoms completely go away in between migraines and the migraines become less frequent with age.[2] Rarely, hemiplegic migraines may cause permanent neurological symptoms, cognitive impairment, stroke, coma, or death.[1][2]

Symptoms

Familial hemiplegic migraine (FHM) commonly begins during childhood or adolescence.[2] It is characterized by migraine with aura along with motor impairment (such as weakness on one side of the body, known as hemiparesis), in addition to “classic” aura which is marked by visual, sensory, and/or speech disturbances. The aura usually occurs before the migraine headache begins, developing over minutes and lasting less than an hour.[1][2] Motor symptoms such as weakness may switch sides between or during attacks, and rarely may affect both sides of the body.[1] While a headache doesn’t always follow, when it does, it causes throbbing pain, nausea, and/or sensitivity to light. The headache can last several hours to a few days[2][3] The symptoms of FHM can be scary and distressing.[1]

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
Migraine with aura
0002077
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
Hemiparesis
Weakness of one side of body
0001269
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
Hemiplegia
Paralysis on one side of body
0002301
Impaired thermal sensitivity
0006901
Nuchal rigidity
0031179
Seesaw nystagmus
0012044
Spontaneous pain sensation
0010833
Tinnitus
Ringing in ears
Ringing in the ears

[ more ]

0000360
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

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

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.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    There are no official treatment guidelines for familial hemiplegic migraine (FHM), and no randomized, controlled trials regarding treatment for hemiplegic migraine have been conducted.[4] People with hemiplegic migraine typically are treated with the same medicines used for typical migraine with aura (for pain, and to stop or prevent migraines). However, medicines that constrict the blood vessels (vasoconstrictors) should be avoided because they may increase the risk for stroke.[1][2][4] Examples of vasoconstrictors that may be used to treat typical migraine with aura include triptans and ergotamines.[1] Treatment may depend on the severity and frequency of attacks as well as specific symptoms, and therefore may vary from person to person. Multiple therapies, either alone or in combination, may need to be tried before finding a treatment regime that is helpful.

    Treatment of sudden hemiplegic migraine “attacks” aims to ease symptoms and may include the use of non-steroidal anti-inflammatory drugs (NSAIDs), anti-nausea medicines (antiemetics), and/or prescription pain medicines.[1][2][5] A medicine called ketamine, ingested through the nose (intranasal), may shorten the duration of aura symptoms if taken as soon as symptoms begin.[1][5][6]

    Examples of medicines that may be used to prevent attacks (prophylactic medicines) may include verapamil, flunarizine, ketamine, lamotrigine, and naloxone. Non-randomized studies have suggested acetazolamide may be effective in preventing attacks in some people with FHM.[1][2][4] Other medicines that may be used to prevent attacks include amitriptyline, topiramate, and valproic acid.[1][2] Individualized antiseizure therapy may additionally be needed for people with FHM who have seizures (particularly those with FHM type 2).[2]

    Management Guidelines

    • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

      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

          • MedlinePlus Genetics contains information on Familial hemiplegic migraine. This website is maintained by the National Library of Medicine.
          • The Migraine Trust, a support organization, offers information on Familial hemiplegic migraine

            In-Depth Information

            • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
            • 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.
            • 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 Familial hemiplegic migraine. Click on the link to view a sample search on this topic.

              References

              1. Kumar A, Arora R. Headache, Migraine Hemiplegic. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; October, 2018; https://www.ncbi.nlm.nih.gov/books/NBK513302/.
              2. Jen JC. Familial hemiplegic migraine. GeneReviews. May 14, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1388/.
              3. Familial hemiplegic migraine. Genetics Home Reference (GHR). January, 2014; https://ghr.nlm.nih.gov/condition/familial-hemiplegic-migraine.
              4. Robertson CE. Hemiplegic migraine. UpToDate. Waltham, MA: UpToDate; 2018; https://www.uptodate.com/contents/hemiplegic-migraine.
              5. Hemiplegic Migraine. American Migraine Foundation. https://americanmigrainefoundation.org/resource-library/hemiplegic-migraine/. Accessed 12/7/2018.
              6. Kaube H, Herzog J, Käufer T, Dichgans M, Diener HC. Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine. Neurology. 2000; 55(1):139. https://n.neurology.org/content/55/1/139.long.

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