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.

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.

Normal Function

Researchers have not determined the role of the PNKD gene (frequently called the MR1 gene) in the human body. This gene is highly active (expressed) in the brain, which suggests that it plays an important role in normal brain function. The protein produced from the PNKD gene may help control the release of chemicals called neurotransmitters, which allow nerve cells (neurons) to communicate with one another.

The PNKD protein is similar to another 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 is toxic to nerve cells (neurons). The PNKD protein may perform a function similar to this protein.

Health Conditions Related to Genetic Changes

Familial paroxysmal nonkinesigenic dyskinesia

At least three mutations in the PNKD gene have been shown to cause familial paroxysmal nonkinesigenic dyskinesia, which is characterized by episodes of involuntary movement. The two most common mutations, each found in several affected families, replace the protein building block (amino acid) alanine with the amino acid valine in the PNKD protein. One of the mutations occurs at position 7 (written as Ala7Val or A7V), and the other mutation is at position 9 (written as Ala9Val or A9V). Research suggests that the PNKD gene mutations alter the structure of the PNKD protein and interfere with its ability to function. It is not known how mutations in the PNKD gene lead to the signs and symptoms of familial paroxysmal nonkinesigenic dyskinesia.

Other Names for This Gene

• brain protein 17
• BRP17
• DKFZp564N1362
• DYT8
• FKSG19
• FPD1
• KIAA1184
• KIPP1184
• MGC31943
• MR-1
• MR-1S
• MR1
• myofibrillogenesis regulator 1
• paroxysmal nonkinesigenic dyskinesia
• PDC
• PKND1
• PNKD_HUMAN

Genomic Location

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.

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