Paroxysmal dyskinesia (ORPHA:1431)
Paroxysmal dyskinesia (PD) is a rare heterogenous group of movement disorders manifesting as abnormal involuntary movements that recur episodically and last only a brief time. PD includes paroxysmal kinesigenic dyskinesia (PKD), paroxysmal non-kinesigenic dyskinesia (PNKD), paroxysmal exertion-induced dyskinesia (PED) and a variant form of PKD, infantile convulsion and choreoathetosis (ICCA syndrome) (see these terms).
Epidemiology
The prevalence of PD is still unknown. The worldwide prevalence of PKD and PNKD is estimated to be 1/150,000 and 1/1,000,000 respectively.
Clinical description
The age of onset is typically in childhood. The paroxysmal movements are mainly dystonic and choreic but can be ballistic or a mixture of these. There is no alteration in consciousness. PD can be classified according to duration and precipitating factors and is thus divided into: paroxysmal kinesigenic dyskinesia (PKD), paroxysmal non-kinesigenic dyskinesia (PNKD) and paroxysmal exertion-induced dyskinesia (PED). Between attacks, patients are generally completely normal and neurological examination is typically normal. Infantile convulsion and choreoathetosis (ICCA syndrome) is considered a variant form of PKD.
Etiology
The exact etiology of PD is still elusive and the causes multifactorial. A number of genes have been associated with different forms of PD, namely: PNKD (2q35) mutations have been found to cause PNKD in families whose attacks can be triggered by caffeine and alcohol, PRRT2 (16p11.2) mutations account for some families with PKD or ICCA syndrome, and SLC2A1 (solute carrier family 2 (facilitated glucose transporter), member 1) (1p34.2 ) mutations have been identified to cause PED.
Diagnostic methods
Diagnosis of PD is essentially based on medical history and clinical examination which includes recordings of dystonia, abnormal postures and tremor, electroencephalogram, brain imaging (computed tomography or magnetic resonance imaging) and blood chemistry. Diagnosis is confirmed by the detection of known pathogenic mutations.
Differential diagnosis
PD can occur secondary to other disorders such as multiple sclerosis, Aicardi-Goutières syndrome (see these terms), myelopathy, cerebral palsy, cerebral infarcts and hemorrhages, focal seizures, encephalitis, radiculopathy, hypoparathyroidism, hypoglycemia and reflex sympathetic dystrophy.
Antenatal diagnosis
Prenatal diagnosis for pregnancies at increased risk for PRRT2, PNKD, and SLC2A1 mutations associated with familial PKD or ICCA syndrome, PNKD, and PED respectively is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis (usually performed at 15-18 weeks' gestation) or chorionic villus sampling (usually performed at 10-12 weeks' gestation). The disease-causing mutation of an affected family member must be identified in the family before prenatal testing can be performed.
Genetic counseling
PD can be sporadic or familial with autosomal dominant inheritance. Genetic counseling should be offered to all patients and families.
Management and treatment
Treatment is different for each of the 4 subtypes. Attacks may be controlled with anticonvulsant drugs such as carbamazepine and phenytoin. Deep brain stimulation may act as a potential therapeutic option in medically refractory PD.
Prognosis
The frequency of attacks typically diminishes with age in the familial cases and the disease often completely remits. There are no long term implications for life expectancy.

                            Last update: 
                            November 2013


                            - Expert reviewer(s): 
                            Dr Sian SPACEY