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X-linked dystonia-parkinsonism(DYT3)

MedGen UID:
326820
Concept ID:
C1839130
Disease or Syndrome
Synonyms: Dystonia 3, torsion, X-linked; DYT-TAF1; DYT3; Lubag; Torsion dystonia-Parkinsonism, Filipino type; X-Linked Dystonia-Parkinsonism Syndrome; X-Linked Torsion Dystonia-Parkinsonism syndrome
SNOMED CT: Lubag (698279003); XDP - X-linked dystonia parkinsonism (698279003); X-linked torsion dystonia parkinsonism syndrome (698279003); X-linked dystonia parkinsonism (698279003); Torsion dystonia parkinsonism Filipino type (698279003)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): TAF1 (Xq13.1)
 
Monarch Initiative: MONDO:0010747
OMIM®: 314250
Orphanet: ORPHA53351

Disease characteristics

Excerpted from the GeneReview: X-Linked Dystonia-Parkinsonism
Individuals with X-linked dystonia-parkinsonism (XDP) have dystonia of varying severity and parkinsonism. XDP afflicts primarily Filipino men and, rarely, women. The mean age of onset in men is 39 years; the clinical course is highly variable with parkinsonism as the initial presenting sign, overshadowed by dystonia as the disease progresses. Features of parkinsonism include resting tremor, bradykinesia, rigidity, postural instability, and severe shuffling gait. The dystonia develops focally, most commonly in the jaw, neck, trunk, and eyes, and less commonly in the limbs, tongue, pharynx, and larynx, the most characteristic being jaw dystonia often progressing to neck dystonia. Individuals with pure parkinsonism have non-disabling symptoms that are only slowly progressive; those who develop a combination of parkinsonism and dystonia can develop multifocal or generalized symptoms within a few years and die prematurely from pneumonia or intercurrent infections. Female carriers are mostly asymptomatic, though a small minority may manifest dystonia, parkinsonism, or chorea. [from GeneReviews]
Authors:
Virgilio Gerald H Evidente   view full author information

Additional description

From MedlinePlus Genetics
X-linked dystonia-parkinsonism is a movement disorder that has been found only in people of Filipino descent. This condition affects men much more often than women.

Parkinsonism is usually the first sign of X-linked dystonia-parkinsonism. Parkinsonism is a group of movement abnormalities including tremors, unusually slow movement (bradykinesia), rigidity, an inability to hold the body upright and balanced (postural instability), and a shuffling gait that can cause recurrent falls.

Later in life, many affected individuals also develop a pattern of involuntary, sustained muscle contractions known as dystonia. The dystonia associated with X-linked dystonia-parkinsonism typically starts in one area, most often the eyes, jaw, or neck, and later spreads to other parts of the body. The continuous muscle cramping and spasms can be disabling. Depending on which muscles are affected, widespread (generalized) dystonia can cause difficulty with speaking, swallowing, coordination, and walking.

The signs and symptoms of X-linked dystonia-parkinsonism vary widely. In the mildest cases, affected individuals have slowly progressive parkinsonism with little or no dystonia. More severe cases involve dystonia that rapidly becomes generalized. These individuals become dependent on others for care within a few years after signs and symptoms appear, and they may die prematurely from breathing difficulties, infections (such as aspiration pneumonia), or other complications.  https://medlineplus.gov/genetics/condition/x-linked-dystonia-parkinsonism

Clinical features

From HPO
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.
Torsion dystonia
MedGen UID:
3941
Concept ID:
C0013423
Disease or Syndrome
Sustained involuntary muscle contractions that produce twisting and repetitive movements of the body.
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.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Parkinsonism with favorable response to dopaminergic medication
MedGen UID:
375989
Concept ID:
C1846868
Disease or Syndrome
Parkinsonism is a clinical syndrome that is a feature of a number of different diseases, including Parkinson disease itself, other neurodegenerative diseases such as progressive supranuclear palsy, and as a side-effect of some neuroleptic medications. Some but not all individuals with Parkinsonism show responsiveness to dopaminergic medication defined as a substantial reduction of amelioration of the component signs of Parkinsonism (including mainly tremor, bradykinesia, rigidity, and postural instability) upon administration of dopaminergic medication.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVX-linked dystonia-parkinsonism
Follow this link to review classifications for X-linked dystonia-parkinsonism in Orphanet.

Professional guidelines

PubMed

Chin HL, Lin CY, Chou OH
Acta Neurol Belg 2023 Feb;123(1):45-55. Epub 2022 Nov 23 doi: 10.1007/s13760-022-02144-3. PMID: 36418540
Jia F, Fellner A, Kumar KR
Genes (Basel) 2022 Mar 7;13(3) doi: 10.3390/genes13030471. PMID: 35328025Free PMC Article
Jamora RD, Diesta CC, Pasco PM, Lee LV
Int J Neurosci 2011;121 Suppl 1:18-21. Epub 2011 Jan 19 doi: 10.3109/00207454.2010.544433. PMID: 21244304

Recent clinical studies

Etiology

Jia F, Fellner A, Kumar KR
Genes (Basel) 2022 Mar 7;13(3) doi: 10.3390/genes13030471. PMID: 35328025Free PMC Article
Zaninotto AL, de Guzman JK, Stipancic KL, Perry BJ, Supnet ML, Go C, Sharma N, Green JR
Parkinsonism Relat Disord 2021 Aug;89:105-110. Epub 2021 Jul 9 doi: 10.1016/j.parkreldis.2021.07.006. PMID: 34274618
Domingo A, Yadav R, Ozelius LJ
J Neural Transm (Vienna) 2021 Apr;128(4):405-416. Epub 2020 Nov 27 doi: 10.1007/s00702-020-02268-x. PMID: 33247415
Weissbach A, Saranza G, Domingo A
J Neural Transm (Vienna) 2021 Apr;128(4):417-429. Epub 2020 Oct 24 doi: 10.1007/s00702-020-02269-w. PMID: 33099685
Blood AJ, Waugh JL, Münte TF, Heldmann M, Domingo A, Klein C, Breiter HC, Lee LV, Rosales RL, Brüggemann N
Neuroimage Clin 2018;17:835-846. Epub 2017 Oct 28 doi: 10.1016/j.nicl.2017.10.025. PMID: 29527488Free PMC Article

Diagnosis

Chin HL, Lin CY, Chou OH
Acta Neurol Belg 2023 Feb;123(1):45-55. Epub 2022 Nov 23 doi: 10.1007/s13760-022-02144-3. PMID: 36418540
Evidente VGH, Evidente DH, Ortega SC, Levine TD, Freeman R, Gibbons CH
Mov Disord 2022 Jan;37(1):130-136. Epub 2021 Sep 28 doi: 10.1002/mds.28801. PMID: 34582053
Zaninotto AL, de Guzman JK, Stipancic KL, Perry BJ, Supnet ML, Go C, Sharma N, Green JR
Parkinsonism Relat Disord 2021 Aug;89:105-110. Epub 2021 Jul 9 doi: 10.1016/j.parkreldis.2021.07.006. PMID: 34274618
Di Lazzaro G, Magrinelli F, Estevez-Fraga C, Valente EM, Pisani A, Bhatia KP
Mov Disord 2021 Jul;36(7):1511-1525. Epub 2021 May 7 doi: 10.1002/mds.28565. PMID: 33960519
Schneider SA, Bhatia KP
Curr Neurol Neurosci Rep 2010 Nov;10(6):431-9. doi: 10.1007/s11910-010-0136-0. PMID: 20694531

Therapy

Niethammer M, Tang CC, Jamora RDG, Vo A, Nguyen N, Ma Y, Peng S, Waugh JL, Westenberger A, Eidelberg D
Ann Neurol 2023 Oct;94(4):684-695. Epub 2023 Jul 11 doi: 10.1002/ana.26732. PMID: 37376770
Hanssen H, Diesta CCE, Heldmann M, Dy J, Tantianpact J, Steinhardt J, Sauza R, Manalo HTS, Sprenger A, Reyes CJ, Tuazon R, Laabs BH, Domingo A, Rosales RL, Klein C, Münte TF, Westenberger A, Oropilla JQ, Brüggemann N
Ann Neurol 2023 May;93(5):999-1011. Epub 2023 Feb 17 doi: 10.1002/ana.26606. PMID: 36646669
Patel AJ, Sarwar AI, Jankovic J, Viswanathan A
World Neurosurg 2014 Jul-Aug;82(1-2):241.e1-4. Epub 2013 Sep 25 doi: 10.1016/j.wneu.2013.09.039. PMID: 24076056
Barrett MJ, Bressman S
Int Rev Neurobiol 2011;98:525-49. doi: 10.1016/B978-0-12-381328-2.00019-5. PMID: 21907099
Jamora RD, Diesta CC, Pasco PM, Lee LV
Int J Neurosci 2011;121 Suppl 1:18-21. Epub 2011 Jan 19 doi: 10.3109/00207454.2010.544433. PMID: 21244304

Prognosis

Burgunder JM
Nat Rev Neurol 2023 Jun;19(6):363-370. Epub 2023 May 18 doi: 10.1038/s41582-023-00811-4. PMID: 37202496
Steinhardt J, Hanssen H, Heldmann M, Sprenger A, Laabs BH, Domingo A, Reyes CJ, Prasuhn J, Brand M, Rosales R, Münte TF, Klein C, Westenberger A, Oropilla JQ, Diesta C, Brüggemann N
Mov Disord 2022 Jul;37(7):1474-1482. Epub 2022 May 2 doi: 10.1002/mds.29033. PMID: 35491955
Brüggemann N, Domingo A, Rasche D, Moll CKE, Rosales RL, Jamora RDG, Hanssen H, Münchau A, Graf J, Weissbach A, Tadic V, Diesta CC, Volkmann J, Kühn A, Münte TF, Tronnier V, Klein C
JAMA Neurol 2019 Feb 1;76(2):211-216. doi: 10.1001/jamaneurol.2018.3777. PMID: 30508028Free PMC Article
Abejero JEE, Jamora RDG, Vesagas TS, Teleg RA, Rosales RL, Anlacan JP, Velasquez MS, Aguilar JA
Parkinsonism Relat Disord 2019 Mar;60:81-86. Epub 2018 Sep 21 doi: 10.1016/j.parkreldis.2018.09.022. PMID: 30262378
Hanssen H, Heldmann M, Prasuhn J, Tronnier V, Rasche D, Diesta CC, Domingo A, Rosales RL, Jamora RD, Klein C, Münte TF, Brüggemann N
Brain 2018 Oct 1;141(10):2995-3008. doi: 10.1093/brain/awy222. PMID: 30169601

Clinical prediction guides

Held A, Adler M, Marques C, Reyes CJ, Kavuturu AS, Quadros ARAA, Ndayambaje IS, Lara E, Ward M, Lagier-Tourenne C, Wainger BJ
Cell Rep 2023 Sep 26;42(9):113046. Epub 2023 Aug 30 doi: 10.1016/j.celrep.2023.113046. PMID: 37651231Free PMC Article
Niethammer M, Tang CC, Jamora RDG, Vo A, Nguyen N, Ma Y, Peng S, Waugh JL, Westenberger A, Eidelberg D
Ann Neurol 2023 Oct;94(4):684-695. Epub 2023 Jul 11 doi: 10.1002/ana.26732. PMID: 37376770
Evidente VGH, Evidente DH, Ortega SC, Levine TD, Freeman R, Gibbons CH
Mov Disord 2022 Jan;37(1):130-136. Epub 2021 Sep 28 doi: 10.1002/mds.28801. PMID: 34582053
Zaninotto AL, de Guzman JK, Stipancic KL, Perry BJ, Supnet ML, Go C, Sharma N, Green JR
Parkinsonism Relat Disord 2021 Aug;89:105-110. Epub 2021 Jul 9 doi: 10.1016/j.parkreldis.2021.07.006. PMID: 34274618
Song PC, Le H, Acuna P, De Guzman JKP, Sharma N, Francouer TN, Dy ME, Go CL
Laryngoscope 2020 Jan;130(1):171-177. Epub 2019 Mar 19 doi: 10.1002/lary.27897. PMID: 30889292

Recent systematic reviews

Over L, Brüggemann N, Lohmann K
J Neuromuscul Dis 2021;8(3):341-356. doi: 10.3233/JND-200598. PMID: 33459660Free PMC Article
Tsuboi T, Wong JK, Okun MS, Ramirez-Zamora A
Parkinsonism Relat Disord 2020 Jan;70:82-93. Epub 2019 Nov 18 doi: 10.1016/j.parkreldis.2019.11.016. PMID: 31767450Free PMC Article
Blanchard A, Ea V, Roubertie A, Martin M, Coquart C, Claustres M, Béroud C, Collod-Béroud G
Hum Mutat 2011 Nov;32(11):1213-24. Epub 2011 Sep 15 doi: 10.1002/humu.21564. PMID: 21793105

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