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Dentatorubral-pallidoluysian atrophy(DRPLA)

MedGen UID:
155630
Concept ID:
C0751781
Disease or Syndrome
Synonyms: Ataxia, chorea, seizures, and dementia; DRPLA; Haw River syndrome; Myoclonic epilepsy with choreoathetosis; Naito Oyanagi disease
SNOMED CT: Dentatorubropallidoluysian degeneration (68116008); Dentatorubropallidoluysian atrophy (68116008); DRPLA - Dentatorubropallidoluysian atrophy (68116008); Dentatorubral-pallidoluysian atrophy (68116008); Dentatorubral-pallidoluysian atrophy (DRPLA) (68116008); Naito-Oyanagi disease (68116008); Haw river syndrome (68116008)
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.
 
Gene (location): ATN1 (12p13.31)
 
Monarch Initiative: MONDO:0007435
OMIM®: 125370
Orphanet: ORPHA101

Definition

Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive disorder of ataxia, myoclonus, epilepsy, and progressive intellectual deterioration in children and ataxia, choreoathetosis, and dementia or character changes in adults. Onset ranges from before age one year to age 72 years; mean age of onset is 31.5 years. The clinical presentation varies depending on the age of onset. The cardinal features in adults are ataxia, choreoathetosis, and dementia. Cardinal features in children are progressive intellectual deterioration, behavioral changes, myoclonus, and epilepsy. [from GeneReviews]

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.
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.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).
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.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
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.
Atrophy of the dentate nucleus
MedGen UID:
341848
Concept ID:
C1857788
Finding
Partial or complete wasting (loss) of dentate nucleus.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDentatorubral-pallidoluysian atrophy
Follow this link to review classifications for Dentatorubral-pallidoluysian atrophy in Orphanet.

Professional guidelines

PubMed

Mongelli A, Sarro L, Rizzo E, Nanetti L, Meucci N, Pezzoli G, Goldwurm S, Taroni F, Mariotti C, Gellera C
Neurosci Lett 2018 Jun 21;678:37-42. Epub 2018 Apr 30 doi: 10.1016/j.neulet.2018.04.044. PMID: 29715545
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Neuropathology 2002 Dec;22(4):317-22. doi: 10.1046/j.1440-1789.2002.00457.x. PMID: 12564773

Recent clinical studies

Etiology

Nowak B, Kozlowska E, Pawlik W, Fiszer A
Mov Disord 2023 Apr;38(4):526-536. Epub 2023 Feb 21 doi: 10.1002/mds.29355. PMID: 36809552
Iwabuchi K, Koyano S, Yagishita S
Neuropathology 2022 Oct;42(5):379-393. Epub 2022 Jul 20 doi: 10.1111/neup.12823. PMID: 35859519
Jellinger KA
J Neural Transm (Vienna) 2022 Jun;129(5-6):521-543. Epub 2021 Aug 7 doi: 10.1007/s00702-021-02392-2. PMID: 34363531
Huang S, Zhu S, Li XJ, Li S
Neuroscientist 2019 Oct;25(5):512-520. Epub 2019 Jan 7 doi: 10.1177/1073858418822993. PMID: 30614396Free PMC Article
Sugiyama A, Sato N, Nakata Y, Kimura Y, Enokizono M, Maekawa T, Kondo M, Takahashi Y, Kuwabara S, Matsuda H
J Neurol 2018 Feb;265(2):322-329. Epub 2017 Dec 13 doi: 10.1007/s00415-017-8705-7. PMID: 29236168

Diagnosis

Jellinger KA
J Neural Transm (Vienna) 2022 Jun;129(5-6):521-543. Epub 2021 Aug 7 doi: 10.1007/s00702-021-02392-2. PMID: 34363531
Carroll LS, Massey TH, Wardle M, Peall KJ
Tremor Other Hyperkinet Mov (N Y) 2018;8:577. Epub 2018 Oct 1 doi: 10.7916/D81N9HST. PMID: 30410817Free PMC Article
Soong BW, Morrison PJ
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Schneider SA, Bhatia KP
Handb Clin Neurol 2011;100:101-12. doi: 10.1016/B978-0-444-52014-2.00005-7. PMID: 21496572
Wardle M, Morris HR, Robertson NP
Mov Disord 2009 Aug 15;24(11):1636-40. doi: 10.1002/mds.22642. PMID: 19514013

Therapy

Qu R, Dai Y, Qu X, Li Y, Shao X, Zhou R, Zhu Y, Chen X
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Neurology 1995 Jan;45(1):143-9. doi: 10.1212/wnl.45.1.143. PMID: 7824105

Prognosis

Iwabuchi K, Koyano S, Yagishita S
Neuropathology 2022 Oct;42(5):379-393. Epub 2022 Jul 20 doi: 10.1111/neup.12823. PMID: 35859519
Nagai S, Saito Y, Endo Y, Saito T, Sugai K, Ishiyama A, Komaki H, Nakagawa E, Sasaki M, Ito K, Saito Y, Sukigara S, Ito M, Goto Y, Ito S, Matsuoka K
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Matilla-Dueñas A
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Hasegawa A, Ikeuchi T, Koike R, Matsubara N, Tsuchiya M, Nozaki H, Homma A, Idezuka J, Nishizawa M, Onodera O
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Clinical prediction guides

Grimaldi S, Cupidi C, Smirne N, Bernardi L, Giacalone F, Piccione G, Basiricò S, Mangano GD, Nardello R, Orsi L, Grosso E, Laganà V, Mitolo M, Maletta RG, Bruni AC
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Sugiyama A, Sato N, Nakata Y, Kimura Y, Enokizono M, Maekawa T, Kondo M, Takahashi Y, Kuwabara S, Matsuda H
J Neurol 2018 Feb;265(2):322-329. Epub 2017 Dec 13 doi: 10.1007/s00415-017-8705-7. PMID: 29236168
Wardle M, Morris HR, Robertson NP
Mov Disord 2009 Aug 15;24(11):1636-40. doi: 10.1002/mds.22642. PMID: 19514013
Ross CA, Wood JD, Schilling G, Peters MF, Nucifora FC Jr, Cooper JK, Sharp AH, Margolis RL, Borchelt DR
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Petronis A, Kennedy JL
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Recent systematic reviews

Wardle M, Morris HR, Robertson NP
Mov Disord 2009 Aug 15;24(11):1636-40. doi: 10.1002/mds.22642. PMID: 19514013

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