Identification of disease-causing mutations in affected families; clarification of new mutations in sporadic cases.
Familial Hemiplegic Migraine Type 2, FHM2 - ATP1A2
According to diagnostic criteria, Familiar Hemiplegic Migraine (FHM) is a migraine with aura in conjunction with a positive family anamnesis (at least one first-degree relative with similar attacks), whereby the aura characteristically includes hemipareses of varying degrees. These pareses can be prolonged, even beyond the duration of the headache. Other focal neurological symptoms such as impaired vision (scintillating scotoma, hemianopsia), sensory disturbance (wandering paresthesia / hypesthesia), or speech disorders may occur in conjunction with aura. Vigilance problems (from light confusion to coma) or rare psychiatric abnormalities have also been described. Magnetic resonance imaging may also reveal cerebellar abnormalities (vermis atrophy in some FHM1 families). Recurrent migraine attacks may begin in a patient’s childhood or teenage years. The severity of the symptoms can vary greatly in affected families.
FHM2 is caused by mutations in the ATP1A2 gene. In addition to the classical FHM phenotype, patients with ATP1A2 mutations show more severe clinical symptoms including epilepsy, reversion or trauma- and/or angiograph-induced comas, ataxia, or mental retardation. Mutations in the ATP1A2 gene have also been found in patients with basilar migraines.
FHM2 follows an autosomal dominant pattern of inheritance and is caused by mutation in the ATP1A2 gene located on chromosome 1 (1q23). A slightly reduced penetrance (87%) has been observed in cases with a familiar accumulation of FHM2.
Rare; however, responsible for up to 13% of sporadic hemiplegic migraines.
All coding exons of the ATP1A2 gene as well as their flanking regions are analyzed using DNA sequencing.
2 - 4 ml of EDTA blood
4 - 6 weeks