Familial/Sporadic hemiplegic migraine type 2 (FHM2/SHM2) is caused by mutations in the ATP1A2 gene. FHM2/SHM2 is a subtype of migraine with aura. Migraine is a severe type of headache in which attacks are associated with intolerance to light and/or sound, nausea and/or vomiting. Sometimes these attacks are preceded by auras; a perceptual disturbance. In the case of FHM2/SHM2 as part of the aura also temporary motor weakness on one side of the body occurs. This weakness in the muscles, which is typical for FHM2/SHM2, might differ in severity from weakness in movement of only the arm or leg to an entire half of the body. People who suffer from FHM2/SHM2 might have additional problems such as epilepsy, permanent mental retardation, confusion and coma. Hemiplegic migraine is subdivided in familial hemiplegic migraine type 2 (FHM2) and sporadic hemiplegic migraine type 2 (SHM2). Distinction can be made on the basis of having respectively a positive or negative family history for hemiplegic migraine. FHM2/SHM2 is a rare disorder, which can be inherited from parent to child (autosomal dominant manner). The average attack frequency lies around 3 attacks per year. Overall FHM/SHM has an estimated prevalence of 0.01%.
In rare cases mutations in ATP1A2 can also cause alternating hemiplegia of childhood 1 (AHC1). There is great overlap in the phenotypic spectrum between FHM2/SHM2 and AHC1. AHC 1 is a neurodevelopmental disorder characterized by repeated episodes of paralysis and other paroxysmal and non-paroxysmal features leading to progressive cognitive and neurological decline. The age of onset of AHC1 is typically before 18 months of age.