U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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]

Additional descriptions

From OMIM
Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder with protean clinical manifestations consisting of various combinations of myoclonus, seizures, ataxia, choreoathetosis, and dementia. The clinical presentation correlates with the size of the causative CAG repeats, and as such, affected family members can present with very different patterns of the disorder (summary by Vinton et al., 2005).  http://www.omim.org/entry/125370
From MedlinePlus Genetics
Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive brain disorder that causes involuntary movements, mental and emotional problems, and a decline in thinking ability. The average age of onset for DRPLA is around 30 years, but this condition can appear any time between infancy and mid-adulthood.

The signs and symptoms of DRPLA differ somewhat between affected children and adults. When DRPLA appears before age 20, it most often involves episodes of involuntary muscle jerking or twitching (myoclonus), seizures, behavioral changes, intellectual disabilities, and problems with balance and coordination (ataxia). When DRPLA begins after age 20, the most frequent signs and symptoms are ataxia, uncontrollable movements of the limbs (choreoathetosis), psychiatric symptoms such as delusions, and deterioration of intellectual function (dementia).  https://medlineplus.gov/genetics/condition/dentatorubral-pallidoluysian-atrophy

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
van de Warrenburg BP, van Gaalen J, Boesch S, Burgunder JM, Dürr A, Giunti P, Klockgether T, Mariotti C, Pandolfo M, Riess O
Eur J Neurol 2014 Apr;21(4):552-62. Epub 2014 Jan 13 doi: 10.1111/ene.12341. PMID: 24418350
Yamada M, Tsuji S, Takahashi H
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
Handb Clin Neurol 2018;155:143-174. doi: 10.1016/B978-0-444-64189-2.00010-X. PMID: 29891056
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
Epileptic Disord 2022 Aug 1;24(4):687-695. doi: 10.1684/epd.2022.1443. PMID: 35770768
Narita Z, Sumiyoshi T
Neuropsychopharmacol Rep 2018 Mar;38(1):44-46. Epub 2018 Feb 5 doi: 10.1002/npr2.12005. PMID: 30106267Free PMC Article
Egawa K, Takahashi Y, Kubota Y, Kubota H, Inoue Y, Fujiwara T, Onodera O
Epilepsia 2008 Dec;49(12):2041-9. Epub 2008 Jun 26 doi: 10.1111/j.1528-1167.2008.01701.x. PMID: 18616556
Ikeuchi T, Igarashi S, Takiyama Y, Onodera O, Oyake M, Takano H, Koide R, Tanaka H, Tsuji S
Am J Hum Genet 1996 Apr;58(4):730-3. PMID: 8644735Free PMC Article
Komure O, Sano A, Nishino N, Yamauchi N, Ueno S, Kondoh K, Sano N, Takahashi M, Murayama N, Kondo I
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
J Neurol 2013 May;260(5):1263-71. Epub 2012 Dec 23 doi: 10.1007/s00415-012-6787-9. PMID: 23263592
Maruyama S, Saito Y, Nakagawa E, Saito T, Komaki H, Sugai K, Sasaki M, Kumada S, Saito Y, Tanaka H, Minami N, Goto Y
J Neurol 2012 Nov;259(11):2329-34. Epub 2012 Apr 18 doi: 10.1007/s00415-012-6493-7. PMID: 22527233
Matilla-Dueñas A
Adv Exp Med Biol 2012;724:172-88. doi: 10.1007/978-1-4614-0653-2_14. PMID: 22411243
Hasegawa A, Ikeuchi T, Koike R, Matsubara N, Tsuchiya M, Nozaki H, Homma A, Idezuka J, Nishizawa M, Onodera O
Mov Disord 2010 Aug 15;25(11):1694-700. doi: 10.1002/mds.23167. PMID: 20589872

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
Mov Disord 2019 Dec;34(12):1919-1924. Epub 2019 Nov 21 doi: 10.1002/mds.27879. PMID: 31755148
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
Philos Trans R Soc Lond B Biol Sci 1999 Jun 29;354(1386):1005-11. doi: 10.1098/rstb.1999.0452. PMID: 10434299Free PMC Article
Petronis A, Kennedy JL
Am J Psychiatry 1995 Feb;152(2):164-72. doi: 10.1176/ajp.152.2.164. PMID: 7840347

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

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...