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Dystonia 12(DYT12)

MedGen UID:
358384
Concept ID:
C1868681
Disease or Syndrome
Synonyms: DYT-ATP1A3; DYT12; Rapid-Onset Dystonia-Parkinsonism
SNOMED CT: Rapid onset dystonia parkinsonism (702323008); DYT12 - dystonia 12 (702323008); Dystonia 12 (702323008)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): ATP1A3 (19q13.2)
 
Monarch Initiative: MONDO:0007496
OMIM®: 128235
Orphanet: ORPHA71517

Definition

ATP1A3-related neurologic disorders represent a clinical continuum in which at least three distinct phenotypes have been delineated: rapid-onset dystonia-parkinsonism (RDP); alternating hemiplegia of childhood (ACH); and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS). However, some affected individuals have intermediate phenotypes or only a few features that do not fit well into one of these major phenotypes. RDP has been characterized by: abrupt onset of dystonia over days to weeks with parkinsonism (primarily bradykinesia and postural instability); common bulbar involvement; and absence or minimal response to an adequate trial of L-dopa therapy, with few exceptions. Often fever, physiologic stress, or alcoholic binges trigger the onset of symptoms. After their initial appearance, symptoms often stabilize with little improvement; occasionally second episodes occur with abrupt worsening of symptoms. Rarely, affected individuals have reported a more gradual onset of symptoms over weeks to months. Anxiety, depression, and seizures have been reported. Age of onset ranges from four to 55 years, although a childhood variation of RDP with onset between ages nine and 14 months has been reported. AHC is a complex neurodevelopmental syndrome most frequently manifesting in infancy or early childhood with paroxysmal episodic neurologic dysfunction including alternating hemiparesis or dystonia, quadriparesis, seizure-like episodes, and oculomotor abnormalities. Episodes can last for minutes, hours, days, or even weeks. Remission of symptoms occurs with sleep and immediately after awakening. Over time, persistent neurologic deficits including oculomotor apraxia, ataxia, choreoathetosis, dystonia, parkinsonism, and cognitive and behavioral dysfunction develop in the majority of those affected; more than 50% develop epilepsy in addition to their episodic movement disorder phenotype. CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) syndrome is characterized by episodes of ataxic encephalopathy and/or weakness during and after a febrile illness. Onset is between ages six months and four years. Some acute symptoms resolve; progression of sensory losses and severity vary. [from GeneReviews]

Additional descriptions

From OMIM
Dystonia-12 (DYT12), also known as rapid-onset dystonia-parkinsonism, is an 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 (summary by Rosewich et al., 2014).  http://www.omim.org/entry/128235
From MedlinePlus Genetics
Rapid-onset dystonia parkinsonism is a rare movement disorder. "Rapid-onset" refers to the abrupt appearance of signs and symptoms over a period of hours to days. Dystonia is a condition characterized by involuntary, sustained muscle contractions. Parkinsonism can include tremors, unusually slow movement (bradykinesia), rigidity, an inability to hold the body upright and balanced (postural instability), and a shuffling walk that can cause recurrent falls.

Rapid-onset dystonia parkinsonism causes movement abnormalities that can make it difficult to walk, talk, and carry out other activities of daily life. In this disorder, dystonia affects the arms and legs, causing muscle cramping and spasms. Facial muscles are often affected, resulting in problems with speech and swallowing. The movement abnormalities associated with rapid-onset dystonia parkinsonism tend to begin near the top of the body and move downward, first affecting the facial muscles, then the arms, and finally the legs.

The signs and symptoms of rapid-onset dystonia parkinsonism most commonly appear in adolescence or young adulthood. In some affected individuals, signs and symptoms can be triggered by an infection, physical stress (such as prolonged exercise), emotional stress, or alcohol consumption. The signs and symptoms tend to stabilize within about a month, but they typically do not improve much after that. In some people with this condition, the movement abnormalities abruptly worsen during a second episode several years later.

Some people with rapid-onset dystonia parkinsonism have been diagnosed with anxiety, social phobias, depression, and seizures. It is unclear whether these disorders are related to the genetic changes that cause rapid-onset dystonia parkinsonism.  https://medlineplus.gov/genetics/condition/rapid-onset-dystonia-parkinsonism

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Mutism
MedGen UID:
6476
Concept ID:
C0026884
Disease or Syndrome
Inability to speak or communicate verbally past the age of typical language development.
Torticollis
MedGen UID:
11859
Concept ID:
C0040485
Sign or Symptom
Torticollis is a twisted neck as a result of shortening of sternocleidomastoid muscle. This short and fibrotic muscle pulls the head laterally and rotates the chin and face to the opposite end. Facial asymmetry may be a manifestation (summary by Engin et al., 1997).
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
Bradykinesia
MedGen UID:
115925
Concept ID:
C0233565
Sign or Symptom
Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).
Parkinsonian disorder
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Postural instability
MedGen UID:
334529
Concept ID:
C1843921
Finding
A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps.
Bulbar signs
MedGen UID:
347246
Concept ID:
C1856507
Finding
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Habitual flow of saliva out of the mouth.
Hypomimic face
MedGen UID:
208827
Concept ID:
C0813217
Finding
A reduced degree of motion of the muscles beneath the skin of the face, often associated with reduced facial crease formation.

Term Hierarchy

Follow this link to review classifications for Dystonia 12 in Orphanet.

Professional guidelines

PubMed

Gorcenco S, Ilinca A, Almasoudi W, Kafantari E, Lindgren AG, Puschmann A
Parkinsonism Relat Disord 2020 Apr;73:72-84. Epub 2020 Mar 2 doi: 10.1016/j.parkreldis.2020.02.015. PMID: 32273229
Scott BL
South Med J 2000 Aug;93(8):746-51. PMID: 10963502
Lees AJ, Turjanski N, Rivest J, Whurr R, Lorch M, Brookes G
J Neurol 1992 Jan;239(1):1-4. doi: 10.1007/BF00839202. PMID: 1541963

Recent clinical studies

Etiology

Dupuch G, Mailly M, Guillaume J, Daval M, Ayache D, Brasnu D
Am J Otolaryngol 2024 Jan-Feb;45(1):104090. Epub 2023 Oct 12 doi: 10.1016/j.amjoto.2023.104090. PMID: 37865985
Morgante F, Matinella A, Andrenelli E, Ricciardi L, Allegra C, Terranova C, Girlanda P, Tinazzi M
Mov Disord 2018 Aug;33(8):1340-1348. Epub 2018 May 8 doi: 10.1002/mds.27402. PMID: 29737565
Espay AJ, Maloney T, Vannest J, Norris MM, Eliassen JC, Neefus E, Allendorfer JB, Chen R, Szaflarski JP
Mov Disord 2018 Jan;33(1):136-145. Epub 2017 Nov 10 doi: 10.1002/mds.27217. PMID: 29124784Free PMC Article
Sweney MT, Newcomb TM, Swoboda KJ
Pediatr Neurol 2015 Jan;52(1):56-64. Epub 2014 Oct 13 doi: 10.1016/j.pediatrneurol.2014.09.015. PMID: 25447930Free PMC Article
Calderon DP, Fremont R, Kraenzlin F, Khodakhah K
Nat Neurosci 2011 Mar;14(3):357-65. Epub 2011 Feb 6 doi: 10.1038/nn.2753. PMID: 21297628Free PMC Article

Diagnosis

Rissardo JP, Caprara ALF
Ann Acad Med Singap 2020 Apr;49(4):236-251. PMID: 32419008
Gorcenco S, Ilinca A, Almasoudi W, Kafantari E, Lindgren AG, Puschmann A
Parkinsonism Relat Disord 2020 Apr;73:72-84. Epub 2020 Mar 2 doi: 10.1016/j.parkreldis.2020.02.015. PMID: 32273229
Niemann N, Jankovic J
Parkinsonism Relat Disord 2019 Oct;67:74-89. Epub 2019 Jun 30 doi: 10.1016/j.parkreldis.2019.06.025. PMID: 31272925
Geyer HL, Bressman SB
Handb Clin Neurol 2011;100:559-62. doi: 10.1016/B978-0-444-52014-2.00040-9. PMID: 21496607
Scott BL
South Med J 2000 Aug;93(8):746-51. PMID: 10963502

Therapy

Patel AT, Lew MF, Dashtipour K, Isaacson S, Hauser RA, Ondo W, Maisonobe P, Wietek S, Rubin B, Brashear A
PLoS One 2021;16(2):e0245827. Epub 2021 Feb 1 doi: 10.1371/journal.pone.0245827. PMID: 33524060Free PMC Article
Rissardo JP, Caprara ALF
Ann Acad Med Singap 2020 Apr;49(4):236-251. PMID: 32419008
Niemann N, Jankovic J
Parkinsonism Relat Disord 2019 Oct;67:74-89. Epub 2019 Jun 30 doi: 10.1016/j.parkreldis.2019.06.025. PMID: 31272925
Scott BL
South Med J 2000 Aug;93(8):746-51. PMID: 10963502
Lees AJ, Turjanski N, Rivest J, Whurr R, Lorch M, Brookes G
J Neurol 1992 Jan;239(1):1-4. doi: 10.1007/BF00839202. PMID: 1541963

Prognosis

Dupuch G, Mailly M, Guillaume J, Daval M, Ayache D, Brasnu D
Am J Otolaryngol 2024 Jan-Feb;45(1):104090. Epub 2023 Oct 12 doi: 10.1016/j.amjoto.2023.104090. PMID: 37865985
Remerand G, Boespflug-Tanguy O, Tonduti D, Touraine R, Rodriguez D, Curie A, Perreton N, Des Portes V, Sarret C; RMLX/AHDS Study Group
Dev Med Child Neurol 2019 Dec;61(12):1439-1447. Epub 2019 Aug 13 doi: 10.1111/dmcn.14332. PMID: 31410843
Rosewich H, Ohlenbusch A, Huppke P, Schlotawa L, Baethmann M, Carrilho I, Fiori S, Lourenço CM, Sawyer S, Steinfeld R, Gärtner J, Brockmann K
Neurology 2014 Mar 18;82(11):945-55. Epub 2014 Feb 12 doi: 10.1212/WNL.0000000000000212. PMID: 24523486
Lohmann K, Uflacker N, Erogullari A, Lohnau T, Winkler S, Dendorfer A, Schneider SA, Osmanovic A, Svetel M, Ferbert A, Zittel S, Kühn AA, Schmidt A, Altenmüller E, Münchau A, Kamm C, Wittstock M, Kupsch A, Moro E, Volkmann J, Kostic V, Kaiser FJ, Klein C, Brüggemann N
Eur J Hum Genet 2012 Feb;20(2):171-5. Epub 2011 Aug 17 doi: 10.1038/ejhg.2011.159. PMID: 21847143Free PMC Article
Yianni J, Bain P, Giladi N, Auca M, Gregory R, Joint C, Nandi D, Stein J, Scott R, Aziz T
Mov Disord 2003 Apr;18(4):436-42. doi: 10.1002/mds.10380. PMID: 12671953

Clinical prediction guides

Yuan Y, Ran L, Lei L, Zhu H, Zhu X, Chen H
Neurodegener Dis 2020;20(2-3):84-89. Epub 2020 Dec 16 doi: 10.1159/000511733. PMID: 33326973
Moya-Mendez ME, Madden LL, Ruckart KW, Downes KM, Cook JF, Snively BM, Brashear A, Haq IU
J Clin Neurosci 2020 Nov;81:133-138. Epub 2020 Oct 5 doi: 10.1016/j.jocn.2020.09.007. PMID: 33222902Free PMC Article
Remerand G, Boespflug-Tanguy O, Tonduti D, Touraine R, Rodriguez D, Curie A, Perreton N, Des Portes V, Sarret C; RMLX/AHDS Study Group
Dev Med Child Neurol 2019 Dec;61(12):1439-1447. Epub 2019 Aug 13 doi: 10.1111/dmcn.14332. PMID: 31410843
Morgante F, Matinella A, Andrenelli E, Ricciardi L, Allegra C, Terranova C, Girlanda P, Tinazzi M
Mov Disord 2018 Aug;33(8):1340-1348. Epub 2018 May 8 doi: 10.1002/mds.27402. PMID: 29737565
Chan J, Brin MF, Fahn S
Mov Disord 1991;6(2):119-26. doi: 10.1002/mds.870060206. PMID: 2057004

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