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.
Familial paroxysmal nonkinesigenic dyskinesia is a very rare disorder. Its prevalence is estimated to be 1 in 5 million people.
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.
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.
Other Names for This Condition
- Familial paroxysmal choreoathetosis
- Mount-Reback syndrome
- Nonkinesigenic choreoathetosis
- Paroxysmal dystonic choreoathetosis
- Paroxysmal nonkinesigenic dyskinesia
Additional Information & Resources
Genetic and Rare Diseases Information Center
Research Studies from ClinicalTrials.gov
Scientific Articles on PubMed
- Bruno MK, Lee HY, Auburger GW, Friedman A, Nielsen JE, Lang AE, Bertini E, Van Bogaert P, Averyanov Y, Hallett M, Gwinn-Hardy K, Sorenson B, Pandolfo M, Kwiecinski H, Servidei S, Fu YH, Ptácek L. Genotype-phenotype correlation of paroxysmal nonkinesigenic dyskinesia. Neurology. 2007 May 22;68(21):1782-9. Citation on PubMed
- Chen DH, Matsushita M, Rainier S, Meaney B, Tisch L, Feleke A, Wolff J, Lipe H, Fink J, Bird TD, Raskind WH. Presence of alanine-to-valine substitutions in myofibrillogenesis regulator 1 in paroxysmal nonkinesigenic dyskinesia: confirmation in 2 kindreds. Arch Neurol. 2005 Apr;62(4):597-600. Citation on PubMed
- Erro R. Familial Paroxysmal Nonkinesigenic Dyskinesia. 2005 Jun 24 [updated 2019 Apr 4]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from http://www.ncbi.nlm.nih.gov/books/NBK1221/ Citation on PubMed
- Gardiner AR, Jaffer F, Dale RC, Labrum R, Erro R, Meyer E, Xiromerisiou G, Stamelou M, Walker M, Kullmann D, Warner T, Jarman P, Hanna M, Kurian MA, Bhatia KP, Houlden H. The clinical and genetic heterogeneity of paroxysmal dyskinesias. Brain. 2015 Dec;138(Pt 12):3567-80. doi: 10.1093/brain/awv310. Epub 2015 Nov 23. Review. Citation on PubMed or Free article on PubMed Central
- Lee HY, Xu Y, Huang Y, Ahn AH, Auburger GW, Pandolfo M, Kwiecinski H, Grimes DA, Lang AE, Nielsen JE, Averyanov Y, Servidei S, Friedman A, Van Bogaert P, Abramowicz MJ, Bruno MK, Sorensen BF, Tang L, Fu YH, Ptácek LJ. The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway. Hum Mol Genet. 2004 Dec 15;13(24):3161-70. Epub 2004 Oct 20. Citation on PubMed
- Shen Y, Ge WP, Li Y, Hirano A, Lee HY, Rohlmann A, Missler M, Tsien RW, Jan LY, Fu YH, Ptáček LJ. Protein mutated in paroxysmal dyskinesia interacts with the active zone protein RIM and suppresses synaptic vesicle exocytosis. Proc Natl Acad Sci U S A. 2015 Mar 10;112(10):2935-41. doi: 10.1073/pnas.1501364112. Epub 2015 Feb 17. Citation on PubMed or Free article on PubMed Central
- Shen Y, Lee HY, Rawson J, Ojha S, Babbitt P, Fu YH, Ptácek LJ. Mutations in PNKD causing paroxysmal dyskinesia alters protein cleavage and stability. Hum Mol Genet. 2011 Jun 15;20(12):2322-32. doi: 10.1093/hmg/ddr125. Epub 2011 Apr 12. Citation on PubMed or Free article on PubMed Central