Familial/Sporadic hemiplegic migraine type 1 (FHM1/SHM1) is a rare disorder. Overall hemiplegic migraine has an estimated prevalence of 0.01%. Clinical diagnosis can be made based on the ICHD criteria of the International Headache Society (IHS) together with physical examination in order to exclude other disorders. Clinical diagnosis together with a mutation in the CACNA1A gene confirm the diagnosis of FHM1/SHM1. FHM1/SHM1 is inherited in an autosomal dominant manner. The average attack frequency of FHM1/SHM1 lies around 3 attacks per year.
Episodic ataxia type 2 (EA2) is a rare disorder characterized by attacks of cerebellar dysfunction. Clinical symptoms together with a mutation in the CACNA1A gene confirm the diagnosis of EA2. The estimated prevalence of EA2 is lower than 1:100000. The frequency of attacks can vary from once a year to multiple attacks per week. Onset is typically during childhood. EA2 is inherited in an autosomal dominant manner.
Spinocerebellar ataxia type 6 (SC6) is an adult-onset slowly progressive neurodegenerative disorder with a normal life-span. Initial symptoms are unsteadiness in gait eventually leading to gait-ataxia, incoordination of the upper limbs, intention tremor and dysarthria. Clinical diagnosis together with a repeat expansion in the CACNA1A gene confirm the diagnosis of SCA6. The age of onset is inversely correlated with the number of expanded CAG repeats. Prevalence of SCA6 differs per geographical area. SCA6 is inherited in an autosomal dominant manner.
Early infantile epileptic encephalopathy type 42 (EIEE42) is a form of epileptic encephalopathy and is characterized by multiple seizure types, epileptiform activity, (severe) developmental delay and often has a poor prognosis. Onset is at birth or in early infancy. Only a few patients have been described with this particular phenotype due to a mutation in CACNA1A.