Familial paroxysmal nonkinesigenic dyskinesia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Familial paroxysmal nonkinesigenic dyskinesia is a disorder of the nervous system that causes episodes of involuntary movement. Paroxysmal indicates that the abnormal movements come and go over time. Nonkinesigenic means that episodes are not triggered by sudden movement. Dyskinesia broadly refers to involuntary movement of the body.

People with familial paroxysmal nonkinesigenic dyskinesia experience episodes of abnormal movement that are brought on by alcohol, caffeine, stress, fatigue, menses, or excitement or develop without a known cause. Episodes are not induced by exercise or sudden movement and do not occur during sleep. An episode is characterized by irregular, jerking or shaking movements that range from mild to severe. In this disorder, the dyskinesia can include slow, prolonged contraction of muscles (dystonia); small, fast, "dance-like" motions (chorea); writhing movements of the limbs (athetosis); and, rarely, flailing movements of the limbs (ballismus). The dyskinesia also affects muscles in the torso and face. The type of abnormal movement varies among affected individuals, even among affected members of the same family. Individuals with familial paroxysmal nonkinesigenic dyskinesia do not lose consciousness during an episode. Most people do not experience any neurological symptoms between episodes.

Individuals with familial paroxysmal nonkinesigenic dyskinesia usually begin to show signs and symptoms of the disorder during childhood or their early teens. Episodes typically last 1 to 4 hours, and the frequency of episodes ranges from several per day to one per year. In some affected individuals, episodes occur less often with age.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the PNKD gene can cause familial paroxysmal nonkinesigenic dyskinesia. The function of the protein produced from the PNKD gene is unknown, although it is thought to play an important role in normal brain function. The PNKD protein may help control the release of chemicals in the brain called neurotransmitters, which allow nerve cells (neurons) to communicate with each other.

The PNKD protein is similar to a protein that helps break down a chemical called methylglyoxal. Methylglyoxal is found in alcoholic beverages, coffee, tea, and cola. Research has demonstrated that this chemical has a toxic effect on neurons. It remains unclear if the PNKD gene is related to the breakdown of methylglyoxal or another substance in the body. How mutations in the PNKD gene lead to the signs and symptoms of familial paroxysmal nonkinesigenic dyskinesia is also unknown.

In some families with familial paroxysmal nonkinesigenic dyskinesia, the condition is not caused by a mutation in the PNKD gene. Researchers suspect that mutations in one or more other genes that have not been identified can cause the condition.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is typically sufficient to cause the disorder. In all reported cases caused by PNKD gene mutations, an affected person has inherited the mutation from one parent. A small number of people with the altered gene have not developed signs and symptoms of the condition, a situation known as reduced penetrance.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Familial paroxysmal nonkinesigenic dyskinesia is a very rare disorder. Its prevalence is estimated to be 1 in 5 million people.

Which doctor should you see?

The suggested department for discussing Familial paroxysmal nonkinesigenic dyskinesia is Dermatology, with a dermatologist as the relevant type of clinician. Dermatologist; paediatric services for children as appropriate.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which features of the skin, hair or nails distinguish the possibilities?
• Would photographs over time help document the changes?
• What should be expected from treatment, and how will irritation or other adverse effects be managed?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Familial paroxysmal nonkinesigenic dyskinesia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.