Familial/Sporadic hemiplegic migraine type 1 (FHM1/SFHM1) is a subtype of migraine with aura. It is characterised by migrainous headaches accompanied by aura symptoms, which include transient motor weakness. The motor weakness is typical for FHM1/SHM1 and the severity may vary from mild paresis to hemiplegia. Additional clinical features can occur, such as chronic progressive ataxia, nystagmus, decreased levels of consciousness and epileptic seizures during an attack have been described. Cerebellar ataxia, and epilepsy can also occur independent of an attack. Furthermore, attacks of a common non-hemiplegic migraine can occur as well. Apart from CACNA1A there are two other genes that can cause hemiplegic migraine. Patients with a mutation in one of these genes often have a more severe phenotype, with extensive motor weakness and brainstem features, confusion and brain oedema.
Episodic ataxia type 2 (EA2) is a characterized by paroxysmal attacks of cerebellar dysfunction such as ataxic gait, incoordination and imbalance. Additional features may be nystagmus, dysarthria, hemiplegia and headache. These symptoms can last from several hours to days. Attacks are often provoked by emotional or physical stress. Interictally patients may suffer from gaze-evoked nystagmus and some patients develop progressive cerebellar ataxia. 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 gait-ataxia, incoordination of the upper limbs, intention tremor, gaze-evoked nystagmus and dysarthria. However also non cerebellar signs have been reported such as, oculomotor disorders, dysphagia and sensory disturbances and pyramidal and extrapyramidal motor deficits.
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, (severe) developmental delay. Seizures typically include focal, tonic and tonic-clonic seizures. Additionally, a range of motor features can occur. The disorder occurs in new-borns usually within the first 3 months of life and the overall prognosis has a poor prognosis.