Genotype-phenotype correlation of paroxysmal nonkinesigenic dyskinesia

Area of Science:

• Genetics
• Neurology
• Rare Diseases

Background:

• Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare disorder featuring episodic hyperkinetic movement attacks.
• Recent research identified mutations in the MR-1 gene as a cause of familial PNKD.

Purpose of the Study:

• To investigate the clinical characteristics of familial dyskinesia.
• To differentiate PNKD associated with MR-1 mutations from other forms of dyskinesia.

Main Methods:

• Clinical review of 14 kindreds with familial dyskinesia.
• Genetic analysis to identify MR-1 mutations in affected families.

Main Results:

• Eight of the 14 kindreds had MR-1 mutations, presenting with early-onset attacks (infancy/childhood) triggered by caffeine, alcohol, or stress.
• Attacks in MR-1 mutation families were choreo-dystonic, lasting 10 minutes to 1 hour, and responded well to benzodiazepines.
• Families without MR-1 mutations showed more variable onset, triggers, symptoms, and medication responses, with some cases resembling paroxysmal exertional dyskinesia.

Conclusions:

• PNKD should be strictly defined by early onset and precipitation by caffeine/alcohol, strongly suggesting MR-1 mutations.
• Families with atypical features and without MR-1 mutations are clinically distinct and may represent other dyskinesia types, such as paroxysmal exertional dyskinesia.