Familial Paroxysmal Nonkinesigenic Dyskinesia

Excerpt

Clinical characteristics: Familial paroxysmal nonkinesigenic dyskinesia (PNKD) is characterized by unilateral or bilateral involuntary movements. Attacks are typically precipitated by coffee, tea, or alcohol; they can also be triggered by excitement, stress, or fatigue, or can be spontaneous. Attacks involve dystonic posturing with choreic and ballistic movements, may be accompanied by a preceding aura, occur while the individual is awake, and are not associated with seizures. Attacks last minutes to hours and rarely occur more than once per day. Attack frequency, duration, severity, and combinations of symptoms vary within and among families. Age of onset is typically in childhood or early teens but can be as late as age 50 years.

Diagnosis/testing: The clinical diagnosis of familial PNKD is suspected in a proband who presents with attacks of dystonia, chorea, and/or ballismus typically provoked by alcohol or caffeine. Identification of a heterozygous pathogenic variant in PNKD by molecular genetic testing confirms the diagnosis.

Management: Treatment of manifestations: Avoid triggers (e.g., caffeine, alcohol, excitement, stress, fatigue). Response to pharmacologic treatment is poor; clonazepam or diazepam can be effective in some individuals. Some individuals have responded to gabapentin, levetiracetam, or acetazolamide.

Surveillance: Monitor medication requirements and dosage.

Genetic counseling: Familial PNKD is inherited in an autosomal dominant manner. To date, all reported individuals with familial PNKD have inherited PNKD from an affected parent. Offspring of an affected individual have a 50% chance of inheriting the PNKD pathogenic variant. Once the PNKD pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.