A machine generated summary based on the work of Chalmer, Mona Ameri; Esserlind, Ann-Louise; Olesen, Jes; Hansen, Thomas Folkmann. 2018  in The Journal of Headache and Pain.

Genetics of migraine aura: an update

DOI: https://doi.org/10.1186/s10194- 020- 01125- 2

Abstract-Summary Of the two main migraine types, migraine with aura and migraine without aura, the genetic underpinning in the former is least understood.

Given the evidence from epidemiological studies in cohorts and families that the

genetic contribution is highest in migraine with aura, this seems paradoxical.

Whereas GWAS in migraine without aura, or the more general diagnosis migraine have already identified dozens of gene variants, the specific hunt for gene variants in migraine with aura has been disappointing.

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The only GWAS specifically investigating migraine with aura yielded only one single associated single nucleotide polymorphism (SNP), near MTDH and PGCP, with genome-wide significance.

Most relevant genetic discoveries related to migraine with aura came from inves- tigating monogenetic syndromes with migraine aura as a prominent phenotype (i.e. FHM, CADASIL and FASPS).

This review will highlight the genetic findings relevant to migraine with aura.

Background Chances of finding a causal mutation in hemiplegic migraine patients in one of the known genes is higher in patients with a lower age of disease onset, when there are more affected family members, and when attacks are (1) triggered by mild head trauma, (2) include confusion, (3) have extensive motor weakness, (4) have symp- toms of brainstem pathology, or (5) are associated with brain edema; mental retar- dation and progressive ataxia are only found in hemiplegic migraine patients with a causal mutation in one of the three known genes.

This might indicate that migraine is a secondary phenomenon due to the progres- sive cerebral vasculopathy seen in patients with RVCL-S. Of note, in another cere- bral small vessel disease, Dutch-type hereditary cerebral amyloid angiopathy (D-CAA) that is caused by a single point mutation (E693Q) in the amyloid precursor protein (APP) gene, there also is an increased prevalence of migraine with aura [10]. In patients with non-small vessel disease familial advanced sleep phase syn- drome (FASPS), which is caused by specific missense mutations in the CSNK1D gene, migraine with aura is prevalent [11].

Conclusion Great effort went into unraveling the genetic architecture of migraine, both of migraine with aura and migraine without aura.

Most knowledge of the genetics of migraine with aura came from studies of monogenic syndromes that pointed to roles for neurotransmission and vasculature in migraine pathophysiology.

By increasing patient cohorts, by testing the contribution or rare(r) variants using recently developed SNP arrays and next generation sequencing approaches and by studying possible epigenetic contributors, it is expected that we will get a better insight of the genetic architecture of migraine, including migraine with aura.

Acknowledgement A machine generated summary based on the work of de Boer, Irene; Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M. 2020 in The Journal of Headache and Pain.

Migrainomics—identifying brain and genetic markers of migraine