Dystonia 12

A hereditary autosomal dominant disorder characterized by abrupt onset of asymmetric dystonia and parkinsonism in young adulthood, often after a trigger such as physical overexertion, trauma, heat, or fever. Affected individuals also show slowly progressive nonparoxysmal neurologic deterioration in a rostrocaudal gradient with prominent bulbar dysfunction. Mutations in the ATP1A3 gene have been identified. OMIM: 128235

Also Known As:

Networked: 60 relevant articles (0 outcomes, 1 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Alternating hemiplegia of childhood
2.	CAPOS syndrome
3.	Cerebellar Ataxia (Dysmetria)
4.	Brain Diseases (Brain Disorder)
5.	Dystonia 12

Experts

1.	Vilsen, Bente: 9 articles (01/2021 - 07/2006)
2.	Ozelius, Laurie J: 5 articles (10/2019 - 07/2004)
3.	Lykke-Hartmann, Karin: 5 articles (05/2017 - 03/2013)
4.	Holm, Rikke: 4 articles (01/2021 - 08/2010)
5.	Khodakhah, Kamran: 4 articles (05/2017 - 04/2012)
6.	Toustrup-Jensen, Mads S: 4 articles (02/2014 - 01/2009)
7.	Nissen, Poul: 3 articles (01/2020 - 01/2009)
8.	Brashear, Allison: 3 articles (10/2019 - 07/2004)
9.	Sweadner, Kathleen J: 3 articles (10/2019 - 07/2004)
10.	Gurrieri, Fiorella: 3 articles (03/2018 - 09/2012)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Dystonia 12:

1.	Proteins (Proteins, Gene)FDA Link 01/01/2020 - "In the past, a great effort has been done to understand the genetic basis of the disease leading to the discovery of mutations in the ATP1A3 gene encoding for the alpha3 subunit of Na+/K+ATPase, a protein already related to another disease named Rapid Onset Dystonia Parkinsonism (RDP). " 01/01/2022 - "From the results of previous studies, we further clarified the clinical characteristics of ATP1A3-related diseases, such as alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism; cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome, and relapsing encephalopathy with cerebellar ataxia, frequency of mutations in different phenotypes and their distribution in gene and protein structures, and differences in mutations in different clinical phenotypes. " 09/01/2012 - "Unlike ATP1A3 mutations that cause rapid-onset dystonia-parkinsonism, AHC-causing mutations in this gene caused consistent reductions in ATPase activity without affecting the level of protein expression. " 05/01/2014 - "Genetic research has shown that mutations that modify the protein-coding sequence of ATP1A3, the gene encoding the α3 subunit of Na(+)/K(+)-ATPase, cause both rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood. "
2.	Adenosine Triphosphatases (ATPase)IBA 10/01/2019 - "Rapid-onset dystonia-parkinsonism (RDP) is caused by mutations in the ATP1A3 gene, which codes for the α-3 subunit of the Na+ /K+ ATPase. " 09/15/2007 - "We report a 38-year-old Korean man with sporadic rapid-onset dystonia-parkinsonism (RDP), who had a Thr 618 Met mutation in the Na(+)/K(+)-ATPase alpha3 subunit gene (ATP1A3). " 07/07/2006 - "Recently, missense mutations in the Na(+),K(+)-ATPase were found associated with familial rapid-onset dystonia parkinsonism (FRDP). " 07/07/2006 - "Mutations Phe785Leu and Thr618Met in Na+,K+-ATPase, associated with familial rapid-onset dystonia parkinsonism, interfere with Na+ interaction by distinct mechanisms." 01/01/2006 - "We report on a 38-year-old patient with rapid-onset dystonia-parkinsonism (RDP) with a missense mutation in the Na/K-ATPase alpha3 subunit (ATP1A3). "
3.	Protein Isoforms (Isoforms)IBA 07/01/2009 - "Mutations in ATP1A3 encoding the alpha3 isoform cause rapid-onset dystonia-parkinsonism (RDP). " 12/01/2007 - "These are Familial Hemiplegic Migraine type 2 and Rapid-Onset Dystonia Parkinsonism, these diseases result from alpha2 and alpha 3 isoform haploinsufficiency, respectively. " 01/01/2016 - "These processes are required for normal brain activity, and in fact autosomal dominant de novo mutations in ATP1A3 encoding the α3 isoform has been found to cause the three neurological diseases Rapid Onset Dystonia Parkinsonism (RDP), Alternating Hemiplegia of Childhood (AHC), and Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS). " 01/01/2016 - "In addition, particular neurological diseases occur as a result of mutations in the α2- (familial hemiplegic migraine type 2) and α3 isoforms (rapid-onset dystonia parkinsonism/alternating hemiplegia of childhood). " 10/01/2015 - "Loss-of-function mutations in the α3 isoform of the sodium pump are responsible for Rapid Onset Dystonia-Parkinsonism (RDP). "
4.	SodiumIBA 01/01/2022 - "In Vivo Brain Sodium Disequilibrium in ATP1A3-Related Rapid-Onset Dystonia-Parkinsonism." 07/01/2009 - "A C-terminal mutation of ATP1A3 underscores the crucial role of sodium affinity in the pathophysiology of rapid-onset dystonia-parkinsonism." 01/01/2017 - "Given the involvement of sodium pumps in movement disorders, such as amyotrophic lateral sclerosis and rapid-onset dystonia parkinsonism, knowledge of their contribution to motor network regulation also has considerable clinical importance. " 04/01/2012 - "It was found that partial selective pharmacological block of the sodium pumps in the cerebellum and basal ganglia of mice recapitulates all of the salient features of DYT12, including dystonia and parkinsonism induced by stress. " 12/01/2014 - "Alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism are two separate movement disorders with different dominant mutations in the same sodium-potassium transporter ATPase subunit gene, ATP1A3. "
5.	Sodium-Potassium-Exchanging ATPase (Sodium, Potassium ATPase)IBA 08/27/2014 - "These findings suggest that persistent high-frequency burst firing of cerebellar neurons caused by sodium pump dysfunction underlies dystonia in this model of DYT12. " 03/01/2018 - "Mutations in the ATP1A3 gene, which encodes the alpha3-subunit of sodium-potassium ATPase, are related to a spectrum of neurological diseases including Rapid onset Dystonia-Parkinsonism (RDP), Alternating Hemiplegia of Childhood (AHC) and Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss (CAPOS) syndrome. " 10/01/2015 - "Loss-of-function mutations in the α3 isoform of the sodium pump are responsible for Rapid Onset Dystonia-Parkinsonism (RDP). " 04/01/2012 - "This (DYT12) is a hereditary dystonia caused by mutations in the α₃ isoform of the sodium potassium adenosine triphosphatase (ATPase) pump (sodium pump), which partially hampers its physiological function. "
6.	Homovanillic AcidIBA 04/01/1998 - "Cerebrospinal fluid homovanillic acid levels in rapid-onset dystonia-parkinsonism." 01/01/1999 - "Rapid-onset dystonia-parkinsonism (RDP) is a genetic movement disorder characterized by abrupt onset over hours to days of bradykinesia, postural instability, dysphagia, dysarthria, and severe dystonic spasms with decreased levels of the dopamine metabolite, homovanillic acid (HVA), in cerebrospinal fluid (CSF). "
7.	Dopamine Plasma Membrane Transport Proteins (Dopamine Transporter)IBA 11/01/2010 - "We cover dopa-responsive dystonia, Wilson's disease, Parkin-, PINK1-, and DJ-1-associated parkinsonism (PARK2, 6, and 7), x-linked dystonia-parkinsonism/Lubag (DYT3), rapid-onset dystonia-parkinsonism (DYT12) and DYT16 dystonia, the syndromes of Neurodegeneration with Brain Iron Accumulation (NBIA) including pantothenate kinase (PANK2)- and PLA2G6 (PARK14)-associated neurodegeneration, neuroferritinopathy, Kufor-Rakeb disease (PARK9) and the recently described SENDA syndrome; FBXO7-associated neurodegeneration (PARK15), autosomal-recessive spastic paraplegia with a thin corpus callosum (SPG11), and dystonia parkinsonism due to mutations in the SLC6A3 gene encoding the dopamine transporter. "
8.	Small Interfering RNA (siRNA)IBA 10/01/2015 - "Aberrant Purkinje cell activity is the cause of dystonia in a shRNA-based mouse model of Rapid Onset Dystonia-Parkinsonism."
9.	Type A Botulinum Toxins (Botox)FDA Link 09/01/1995 - "The effects of botulinum toxin type A were studied in 33 patients with dystonia (12 blepharospasms, 10 hemifacial spasms and 11 spasmodic torticollis). "
10.	PotassiumIBA 12/01/2014 - "Alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism are two separate movement disorders with different dominant mutations in the same sodium-potassium transporter ATPase subunit gene, ATP1A3. "

Therapies and Procedures

1.	Deep Brain Stimulation 09/01/2023 - "Centromedian-parafascicular complex deep brain stimulation improves motor symptoms in rapid onset Dystonia-Parkinsonism (DYT12-ATP1A3)." 11/01/2019 - "Electrodes (n = 60) for deep brain stimulation were implanted in the STN of patients (n = 30; median age 57 yr) with Parkinson disease (n = 29) or rapid-onset dystonia parkinsonism (n = 1). " 07/01/2018 - "Atypical Presentation of Rapid-onset Dystonia-parkinsonism (DYT12) Unresponsive to Deep Brain Stimulation of the Subthalamic Nucleus." 03/01/2015 - "Failure of Pallidal Deep Brain Stimulation in a Case of Rapid-Onset Dystonia Parkinsonism (DYT12)."
2.	Electrodes (Electrode) 11/01/2019 - "Electrodes (n = 60) for deep brain stimulation were implanted in the STN of patients (n = 30; median age 57 yr) with Parkinson disease (n = 29) or rapid-onset dystonia parkinsonism (n = 1). "
3.	General Anesthesia 03/30/2021 - "We report the case of a 14-year-old patient diagnosed with rapid-onset dystonia-parkinsonism who was scheduled for injection of botulinum toxin in his upper limbs under general anesthesia. "
4.	Cannula 12/01/2020 - "In order to locally block the α3-subunit in the basal ganglia and the cerebellum, which are the two brain structures believed to be heavily involved in the pathogenesis of rapid-onset dystonia-parkinsonism, a bilateral cannula is stereotaxically implanted into the striatum and an additional single cannula is introduced into the cerebellum. "