ABSTRACT
While genetic research in primary headaches has mainly focused on migraine, more recently, genetic susceptibility in cluster headache (CH) and tension-type headache are also receiving attention. Migraine without aura (MO) and migraine with aura (MA), the two most common subtypes of migraine, are genetically complex, due to the combination of genes and environmental factors involved. By investigating familial hemiplegic migraine (FHM), a rare subtype of MA, with an autosomal dominant mode of inheritance, the identification of migraine genes was facilitated. In FHM, aura consists of hemiparesis, in addition to typical (visual) aura symptoms, preceding the headache phase. There must be at least one family member with identical attacks. FHM attacks often resemble those of basilar migraine (1), and the headache and aura symptoms, apart from the hemiparesis, are identical to those of MA (2). Some patients have atypical attacks, either with a prolonged aura lasting up to five days or with signs of diffuse encephalopathy, expressed as confusion or coma, fever, and sometimes epileptic seizures. Attacks may be triggered by head trauma. Very often an initial diagnosis of epilepsy is made. Patients with FHM and their relatives are at increased risk for ‘‘nonhemiplegic’’ typical MA, but not
MO attacks (3). Sporadic cases with FHM symptomatology [sporadic hemiplegic migraine (SHM)] exist, virtually always with other aura symptoms as well (visual, sensory, and aphasic) (4). The first gene for FHM (FHM1), CACNA1A, was identified in 1996 on the short arm of chromosome 19 (5). With the identification of the second FHM (FHM2) gene (ATP1A2, on the long arm of chromosome 1, identified in 2003) (6) and the results of several genome screens in MO and MA patients, important progress has been made toward elucidating the genetic causes of migraine.
THE CLINICAL SPECTRUM OF THE CACNA1A GENE MUTATIONS
