An association between migraine and vertigo was first noted in the 19th century when Liveing reported their connection in his classic book “On Megrim: Sick headaches and some allied health disorders.”1
Since that time, there have been numerous reports documenting that vertigo is much more common in patients with migraine than in controls and, conversely, that migraine is much more common in patients presenting with vertigo than in controls.2–6
Overall, vertigo occurs in about a quarter of patients with migraine headaches,7
probably about the same frequency as that of the classic migraine visual aura. Vertigo can occur during the headache but often occurs during headache-free intervals. Follow-up studies in patients with benign paroxysmal vertigo of childhood8, 9
and benign recurrent vertigo in adults10, 11
have shown that both of these disorders are usually associated with migraine, so-called migraine-associated vertigo (MAV).
For migraine in general, numerous studies over the years have documented familial aggregation of migraine symptoms and some have suggested that a positive family history should be part of the diagnostic criteria for migraine.12
In nearly all studies, the frequency of a positive family history in patients with migraine headaches was significantly greater than in controls. Studies in monozygotic and dizygotic twins have also supported a strong genetic component for migraine.12
The fact that the prevalence of migraine in African and Asian populations is lower than in European and North American populations also favors a genetic component.13
Despite this strong evidence for a genetic component for migraine, no predisposing genes have been identified for the common migraine syndromes, migraine with aura (MA) and migraine without aura (MO). Insight into the molecular mechanisms of migraine was provided by identification of mutations associated with a rare subtype of MA, familial hemiplegic migraine (FHM). This autosomal dominant disorder is characterized by headache attacks preceded or accompanied by episodes of hemiplegia, sometimes lasting days. Mutations in the ion channel genes CACNA1A14
and in the sodium-potassium transporter gene ATP1A216
have been found in families with FHM. Within these reported families, some family members with FHM mutations report only MO or MA.
Classical segregation analysis in families with common migraine syndromes does not suggest an autosomal dominant or autosomal recessive inheritance but rather suggests a polygenetic inheritance.17–19
However, segregation analysis cannot detect whether one phenotype is caused by different genotypes and does not analyze for reduced penetrance. Clearly this type of analysis does not exclude the possibility that some families such as those with MAV may have a simple Mendelian pattern of inheritance. To assess this possibility, we performed a detailed phenotype analysis of a large multigenerational family with MAV and combined this with a thorough characterization of identity-by-descent (IBD) analysis using dense single nucleotide polymorphism (SNP) arrays.