Clinical Characteristics

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 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 voluntary muscle movement (ataxia), involuntary eye movement (nystagmus), as well as decreased levels of consciousness and epileptic seizures during an attack have been described.

Episodic ataxia type 2 (EA2) is a characterized by sudden attacks of cerebellar dysfunction such as gait abnormalities, incoordination and imbalance. These symptoms can last from several hours to days. Attacks are often provoked by emotional or physical stress. Between attacks patients may suffer from gaze-evoked nystagmus and some patients develop progressive cerebellar ataxia (lack of voluntary coordination of muscle movement). Patients in some families might have both, episodes of ataxia and hemiplegic migraine.

Spinocerebellar ataxia type 6 (SC6) is also characterized by cerebellar dysfunction. Typical symptoms are also gait abnormalities, incoordination of the upper limbs, intention tremor, gaze-evoked nystagmus (involuntary eye movement) and dysarthria (difficulty speaking). However also non cerebellar signs have been reported such as, dysphagia (difficulty swallowing), sensory disturbances, and repetitive muscle contractions.

Early infantile epileptic encephalopathy type 42 (EIEE42) is a severe neurological disorder. EIEE42 is a form of epileptic encephalopathy and is characterized by multiple seizure types, epileptiform activity on EEG and (severe) developmental delay. Seizures typically include focal, tonic and tonic-clonic seizures. The disorder occurs in new-borns usually within the first 3 months of life and the overall prognosis has a poor prognosis.