Encyclopedia
Familial hemiplegic migraine 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 can be triggered by certain foods, emotional stress, and minor head trauma. Each headache may last from a few hours to a few days.
- genetic conditions
1. Introduction
A shortage of adrenal hormones (adrenal insufficiency) causes the signs and symptoms of familial glucocorticoid deficiency. These signs and symptoms often begin in infancy or early childhood. Most affected children first develop low blood sugar (hypoglycemia). These hypoglycemic children can fail to grow and gain weight at the expected rate (failure to thrive). If left untreated, hypoglycemia can lead to seizures, learning difficulties, and other neurological problems. Hypoglycemia that is left untreated for prolonged periods can lead to neurological damage and death. Other features of familial glucocorticoid deficiency can include recurrent infections and skin coloring darker than that of other family members (hyperpigmentation).
There are multiple types of familial glucocorticoid deficiency, which are distinguished by their genetic cause.
2. Frequency
The worldwide prevalence of familial hemiplegic migraine is unknown. Studies suggest that in Denmark about 1 in 10,000 people have hemiplegic migraine and that the condition occurs equally in families with multiple affected individuals (familial hemiplegic migraine) and in individuals with no family history of the condition (sporadic hemiplegic migraine). Like other forms of migraine, familial hemiplegic migraine affects females more often than males.
3. Causes
Mutations in the CACNA1A, ATP1A2, SCN1A, and PRRT2 genes have been found to cause familial hemiplegic migraine. The first three genes provide instructions for making proteins that are involved in the transport of charged atoms (ions) across cell membranes. The movement of these ions is critical for normal signaling between nerve cells (neurons) in the brain and other parts of the nervous system. The function of the protein produced from the PRRT2 gene is unknown, although studies suggest it interacts with a protein that helps control signaling between neurons.
Communication between neurons depends on chemicals called neurotransmitters, which are released from one neuron and taken up by neighboring neurons. Researchers believe that mutations in the CACNA1A, ATP1A2, and SCN1A genes can upset the balance of ions in neurons, which disrupts the normal release and uptake of certain neurotransmitters in the brain. Although the mechanism is unknown, researchers speculate that mutations in the PRRT2 gene, which reduce the amount of PRRT2 protein, also disrupt normal control of neurotransmitter release. The resulting changes in signaling between neurons lead people with familial hemiplegic migraine to develop these severe headaches.
There is little evidence that mutations in the CACNA1A, ATP1A2, SCN1A, and PRRT2 genes play a role in common migraines, which affect millions of people each year. Researchers are searching for additional genetic changes that may underlie rare types of migraine, such as familial hemiplegic migraine, as well as the more common forms of migraine.
5. Inheritance
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, affected individuals have one affected parent. However, some people who inherit an altered gene never develop features of familial hemiplegic migraine. (This situation is known as reduced penetrance.) A related condition, sporadic hemiplegic migraine, has identical signs and symptoms but occurs in individuals with no history of the disorder in their family.
6. Other Names for This Condition
- hemiplegic migraine, familial
- hemiplegic-ophthalmoplegic migraine
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/familial-hemiplegic-migraine
References
- Black DF. Sporadic and familial hemiplegic migraine: diagnosis and treatment. Semin Neurol. 2006 Apr;26(2):208-16. Review.
- Colson NJ, Fernandez F, Lea RA, Griffiths LR. The search for migraine genes:an overview of current knowledge. Cell Mol Life Sci. 2007 Feb;64(3):331-44.Review.
- Dale RC, Gardiner A, Antony J, Houlden H. Familial PRRT2 mutation withheterogeneous paroxysmal disorders including paroxysmal torticollis andhemiplegic migraine. Dev Med Child Neurol. 2012 Oct;54(10):958-60. doi:10.1111/j.1469-8749.2012.04394.x.
- Jen JC. Familial Hemiplegic Migraine. 2001 Jul 17 [updated 2015 May 14]. In:Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A,editors. GeneReviews® [Internet]. Seattle (WA): University of Washington,Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1388/
- Pietrobon D. Familial hemiplegic migraine. Neurotherapeutics. 2007Apr;4(2):274-84. Review.
- Ramagopalan SV, Ramscar NE, Cader MZ. Molecular mechanisms of migraine? JNeurol. 2007 Dec;254(12):1629-35.
- Riant F, Roze E, Barbance C, Méneret A, Guyant-Maréchal L, Lucas C, Sabouraud P, Trébuchon A, Depienne C, Tournier-Lasserve E. PRRT2 mutations cause hemiplegicmigraine. Neurology. 2012 Nov 20;79(21):2122-4. doi:10.1212/WNL.0b013e3182752cb8.
- van de Ven RC, Kaja S, Plomp JJ, Frants RR, van den Maagdenberg AM, FerrariMD. Genetic models of migraine. Arch Neurol. 2007 May;64(5):643-6. Review.
- van den Maagdenberg AM, Haan J, Terwindt GM, Ferrari MD. Migraine: genemutations and functional consequences. Curr Opin Neurol. 2007 Jun;20(3):299-305. Review.
