Review Outlines Combined Genetic, Environmental Susceptibility to Vestibular Migraine

Although there is limited available evidence on the heritability of vestibular migraine (VM), variability in prevalence depending on ethnicity and geographic location suggests a combined genetic and environmental contribution to VM, according to the results of a systematic review.

Patients with VM experience sensorial symptoms that involve the vestibular system. Specifically, VM is characterized by recurrent bouts of vertigo, a current or past history of migraine, and the simultaneous occurrence of both symptoms during an episode.

In approximately one-third of migraineurs, headaches are preceded by transient focal sensorial symptoms, or auras, involving visual and hearing systems, the authors wrote. “Epidemiological evidence supports that familial aggregation with an early disease onset, particularly for the aura subtype, indicating a higher genetic susceptibility in migraine with aura.”

VM is also one of the most common causes of recurrent vertigo, although the condition is largely underdiagnosed because of variability and overlap of symptoms with other vertigo causes.

To assess evidence in scientific publications on the role of inheritance in VM, the researchers gathered information about the prevalence of VM in different populations. Article searchers were conducted in the PubMed and Scopus databases in May of 2020. All animal studies, studies conducted in pediatric populations, or studies published in languages other than English or Spanish were excluded.

The final analysis included 31 studies with a combined sample size of 41,127 individuals. The majority of the studies (n = 24) were descriptive epidemiological studies that estimated the prevalence of VM in different populations. The remaining studies were genetic association studies conducted in families or case-control in candidate genes.

The researchers found:

• The estimated prevalence of VM was different between Black (3.13%), White (2.64%), and Asian (1.07%) ethnicities
• The reported prevalence of VM in patients with migraine is higher in European countries (21%) than in Asian countries (10%)
• The prevalence of the migraine-vertigo association in families is 4 to 10 times higher than that reported in the general population (sibling recurrence risk ratio λs = 4.31-10.42)
• The age of onset is lower in patients with simultaneous onset of symptoms and in those who have familial history for migraine and/or vertigo, suggesting anticipation
• Familial studies showed a higher prevalence of the migraine-vertigo association than the observed prevalence of that association in the general population (3.2%) and also higher than VM in the general population (2.7%)

“Although some genetic studies have reported few allelic variants associated to VM, replication studies are needed to validate these results,” authors wrote.

Several pieces of evidence also support heritability in complex traits like vestibular disorders. These include:

• Differences in the prevalence of the condition according to the ethnic background
• Familial aggregation with early onset and anticipation
• High concordance of the phenotype in monozygotic (identical) twins and adoptees with biological parents when they are compared with dizygotic (fraternal) twins or adoptive parents

Because current diagnostic criteria for VM were published in 2012, previous studies may have applied different criteria, marking a limitation to the review. The variability acted as a selection bias that may have influenced estimated prevalence, potentially limiting comparability between studies.

“There is a need to perform twins and adoptees studies to estimate heritability in VM,” the researchers conclude. “Therefore, whole genome sequencing studies in multi-case families are needed to find genetic variants conferring susceptibility to this disease.”

Reference

Paz-Tamayo A, Parez-Carpena P, Lopez-Escamez JA. Systematic review of prevalence studies and familiar aggregation in vestibular migraine. Front Genet. Published online August 31, 2020. doi:10.3389/fgene.2020.00954