The genetic relationship between epilepsy and hemiplegic migraine

Abstract

Epilepsy and migraine are common diseases of the nervous system and share genetic and pathophysiological mechanisms. Familial hemiplegic migraine is an autosomal dominant disease. It is often used as a model of migraine. Four genes often contain one or more mutations in both epilepsy and hemiplegic migraine patients (ie, CACNA1A, ATP1A2, SCN1A, and PRRT2). A better understanding of the shared genetics of epilepsy and hemiplegic migraine may reveal new strategic directions for research and treatment of both the disorders.

Familial Cortical Myoclonic Tremor and Epilepsy, an Enigmatic Disorder: From Phenotypes to Pathophysiology and Genetics. A Systematic Review

“… 14 SCA type 6 is caused by a CAG repeat in a calcium channel CACNA1A heavily expressed in the cerebellum. 92 Other observations that might also point to a trinucleotide repeat expansion or channelopathy underlying FCMTE include in Asian FCMTE pedigrees, progressively earlier onset of the disease with increasing severity in successive generations 19 – 21 ; presence of migraine 15 – 18 analogues to hemiplegic migraine with mutations in calcium channels 93 ; and the recognition that certain epilepsy syndromes are channelopathies. 45 , 94 Recently, an autosomal recessive form of FCMTE has been recognized with a single base pair deletion in CNTN2 , crucial for the stability of potassium channels.…”

The Genetic Relationship between Paroxysmal Movement Disorders and Epilepsy

“…SNAP25 alters neurotransmitter release and calcium channel dynamics, which affects vesicle synapse accordingly [40]. It has been suggested that PRRT2 mutations impair SNAP25 function by altering Cav2.1 activity, which lead to neuronal hyperexcitability and subsequently cause epilepsy, PKD, or other paroxysmal movement disorders [41]. In addition to the relation between PRRT2 and SNAP25, many studies proposed that PRRT2 has postsynaptic roles in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor signaling [42,43].…”

“…1. Familial hemiplegic migraine and epilepsy CACNA1A, ATP1A2, SCN1A, and PRRT2 genes often contain one or more mutations in both epilepsy and hemiplegic migraine patients [8,21,41]. These shared mutations identified in epilepsy and migraine cases suggest that there is a common genetic basis for these conditions.…”

“…These shared mutations identified in epilepsy and migraine cases suggest that there is a common genetic basis for these conditions. There are two categories of migraine: migraine with and without aura, and hemiplegic migraine is a rare form of migraine with aura [41].…”

“…Since maintaining the correct concentrations of Na + and K + via the Na + /K + ATPase system is crucial for the ability of astrocytes to clear extracellular glutamic acid, an abnormal Na + /K + ATPase system function disrupts the K + gradient and impairs glutamate clearance, which likely contributes to the development of familial hemiplegic migraine and epilepsy [41].…”