Familial/Sporadic hemiplegic migraine type 1 (FHM1/SHM1) is caused by mutations in the CACNA1A gene. FHM1/SHM1 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 FHM1/SHM1 as part of the aura, also temporary motor weakness on one side of the body occurs. This is a weakness in the muscles, which is typical for FHM1/SHM1 and 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 FHM1/SHM1 might have additional problems such as chronic progressive lack in coordination of muscle movement (ataxia), involuntary eye movement (nystagmus), as well as decreased levels of consciousness and epileptic seizures during an attack have been described.
Hemiplegic migraine is subdivided in familial hemiplegic migraine type 1 (FHM1) and sporadic hemiplegic migraine type 1 (SHM1). Distinction can be made on the basis of having respectively a positive or negative family history for hemiplegic migraine. FHM1/SHM1 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%.
Episodic ataxia type 2 (EA2) is a rare disorder characterized by attacks of cerebellar dysfunction. The cerebellum is a part of the brain that is involved in motor control. Therefore, typically motor control of patients is affected. Symptoms are gait abnormalities, incoordination and imbalance. Additional features may be involuntary eye movement (nystagmus), problems with the muscles that affect speech (dysarthria), motor weakness on one side of the body and headache. These symptoms can last from several hours to days. 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 can be inherited from parent to child (autosomal dominant manner).
Spinocerebellar ataxia type 6 (SC6) is an adult-onset slowly progressive neurodegenerative disorder with a normal life-span. Many key symptoms of SCA6 are also based on cerebellar dysfunction. Symptoms are gait abnormalities, incoordination of the upper limbs, intention tremor and problems with the muscles that affect speech (dysarthria). Clinical diagnosis together with a repeat expansion in the CACNA1A gene confirm the diagnosis of SCA6. The age of onset is usually around the 4th and 5th decade of life and is inversely correlated with the number expanded of CAG repeats. Prevalence of SCA6 differs per geographical area. SCA6 can be inherited from parent to child (autosomal dominant manner).
Early infantile epileptic encephalopathy type 42 (EIEE42). EIEE42 is a form of epileptic encephalopathy and is characterized by multiple seizure types, epileptiform activity on EEG, (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.