Clinical Guidance

There are currently no known genotype-phenotype correlations.

Source: GeneReviews — "Familial Paroxysmal Nonkinesigenic Dyskinesia"

Penetrance

calculated the penetrance of familial PNKD in individuals with PNKD pathogenic variants to be 98%; the asymptomatic individual in the study was too young to be considered unaffected.

Source: GeneReviews — "Familial Paroxysmal Nonkinesigenic Dyskinesia"

Diagnostic Criteria

Suggestive Findings

Familial paroxysmal nonkinesigenic dyskinesia (PNKD) should be suspected in individuals with the following features:

• Attacks:

• Of dystonia, chorea, and/or ballismus, with onset during infancy

• That can be provoked by alcohol or caffeine

• Not typically triggered by sudden movement or sustained exercise

• Lasting several minutes to hours

• Rarely occurring more than once per day

• No loss of consciousness during an attack

• Poor response to pharmacologic treatment (although clonazepam or diazepam can be effective)

• Normal:

• Interictal neurologic examination

• Brain MRI

• EEG

• Family history consistent with autosomal dominant inheritance

Establishing the Diagnosis

The diagnosis of familial PNKD is established in an individual with the above by identification of a heterozygous pathogenic variant...

Source: GeneReviews — "Familial Paroxysmal Nonkinesigenic Dyskinesia"

Differential Diagnosis

Paroxysmal dyskinesias have been reported in individuals with the following disorders (brain MRI examination is important to rule out these etiologies): • Basal ganglia lesions caused by multiple sclerosis • Tumors • Vascular lesions including moyamoya disease • Penetrating brain injury (e.g., right frontal) • Central pontine myelinolysis Focal seizures can present with paroxysms of dystonia; EEG is an essential part of the investigations. Autoimmune disorders. Dyskinesias seen in association with rheumatic fever (Sydenham's chorea) are associated with a raised anti-streptolysin O (ASO) titer and normal cerebrospinal fluid. PNKD has also been reported as a manifestation of antiphospholipid antibody syndrome . Chorea gravidarum can present with paroxysms of chorea in the first trimester of pregnancy and usually resolves after delivery. Other. Paroxysmal chorea can also be seen with systemic lupus erythematosus, diabetes mellitus, hypoparathyroidism, pseudohypoparathyroidism, and thyrotoxicosis. The relevant laboratory testing should be done if these etiologies are being considered . Inherited Causes of Paroxysmal Dyskinesia Table 2. Disorders to Consider in the Differential Diagnosis of Familial PNKD

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with familial paroxysmal nonkinesigenic dyskinesia (PNKD), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Referral to a neurologist for discussion of treatment options

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Avoid triggers (e.g., caffeine, alcohol). Response to pharmacologic treatment is poor; however, clonazepam or diazepam can be effective in at least 50% of individuals with PNKD, although response may decrease over time.

• A child age four years with familial PNKD responded to gabapentin .

• reported individuals from a family with PNKD who responded favorably to levetiracetam.

• reported individuals with severe PNKD who responded to acetazolamide.

Surveillance

Monitor medication requirements and dosage.

Evaluation of Relatives at Risk

See for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Pregnant women who are on anticonvulsant therapy for familial PNKD are advised to take folic acid (5 mg/day). Because of the risk of teratogenic effects related to anticonvulsants, women with mild symptoms related to familial PNKD may consider discontinuing anticonvulsant therapy during pregnancy. See MotherToBaby for access further information on medication use during pregnancy.

Therapies Under Investigation

...

Source: GeneReviews — "Familial Paroxysmal Nonkinesigenic Dyskinesia"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Familial Paroxysmal Nonkinesigenic Dyskinesia"

Surveillance Guidelines

Monitor medication requirements and dosage.

Source: GeneReviews — "Familial Paroxysmal Nonkinesigenic Dyskinesia"