Paroxysmal exertion-induced dyskinesia

Alternate names

DYT18; PED; Paroxysmal exercise-induced dystonia; Dystonia 18; DYT-SLC2A1

Definition

Paroxysmal exertion-induced dyskinesia (PED) is a form of paroxysmal dyskinesia , characterized by painless attacks of dystonia of the extremities triggered by prolonged physical activities.

Epidemiology

The prevalence is unknown but 20 sporadic cases and 9 families have been described to date.

Cause

• The pathophysiology of PED is still unknown but some familial cases were found to be associated with mutations in the SLC2A1 (solute carrier family 2 (facilitated glucose transporter), member 1) gene (1p34.2).
• SLC2A1 encodes the glucose transporter GLUT1.

Gene mutations

• All mutations in this gene responsible for PED have been found to affect the ability of GLUT1 to transport glucose.
• It has thus been proposed that an energy deficiency upon exertion caused by a reduced glucose transport rate is a cause of this paroxysmal movement disorder in SLC2A1 related cases.

Inheritance

Sporadic and familial cases with autosomal dominant mode of inheritance have been reported for PED. Genetic counseling should be offered to patients and families.

onset

The age of onset is usually in childhood, but may range from 1 to 30 years.

Signs and symptoms

• PED is characterized by dyskinesias induced by prolonged exercise of 15-60 minutes of duration.
• The attacks last between 5 minutes and 2 hours and are typically restricted to the exercised limbs.
• The dystonic movements are usually bilateral and are aggravated by cold, psychological stress, fatigue and lack of sleep.
• The frequency of attacks varies between one per day to one per month.
• Brisk, deep tendon reflexes, developmental delay and intellectual disability (most frequently mild) may also be observed.
• In some familial forms, epilepsy or migraine can co-occur.
• PED can be associated with paroxysmal dystonic choreathetosis with episodic ataxia and spasticity, benign familial infantile seizures (BFIE), infantile convulsions and choreoathetosis (ICCA syndrome) or rolandic epilepsy - paroxysmal exercise-induced dystonia - writer's cramp .

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Choreoathetosis
• Paroxysmal dyskinesia

30%-79% of people have these symptoms

• Generalized non-motor (absence) seizure(Brief seizures with staring spells)
• Hyperactive deep tendon reflexes
• Paresthesia(Pins and needles feeling)
• Torsion dystonia

5%-29% of people have these symptoms

• Aggressive behavior(Aggression)
• Ataxia
• Irritability(Irritable)
• Specific learning disability

1%-4% of people have these symptoms

• Intellectual disability, mild(Mental retardation, borderline-mild)
• Lower limb spasticity

Diagnosis

• The diagnosis of PED relies on clinical examination and laboratory investigations showing hypoglycorrhachia and hypoglycemia. Electroencephalography (EEG) and brain imaging are normal.
• The diagnosis is confirmed by molecular genetic testing of SLC2A1 gene.

Antenatal diagnosis

• Prenatal diagnosis for pregnancies at increased risk of PED 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.

Management and treatment

• There is no specific cure or treatment but avoiding precipitating events such as prolonged physical exercise may largely improve the symptoms.
• Moreover, a ketogenic diet for patients may prevent attacks and may lead to improvement of developmental delay in affected children.

NIH genetic and rare disease info

• NIH info on Paroxysmal exertion-induced dyskinesia

Paroxysmal exertion-induced dyskinesia is a rare disease.