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Dystonia 30(DYT30)

MedGen UID:
1785079
Concept ID:
C5543312
Disease or Syndrome
Synonyms: DYSTONIA 30; DYT30
 
Gene (location): VPS16 (20p13)
 
Monarch Initiative: MONDO:0025691
OMIM®: 619291

Definition

Dystonia-30 (DYT30) is an autosomal dominant neurologic disorder characterized by the onset of symptoms in the first decades of life. Patients present with oromandibular, cervical, bulbar, or upper limb dystonia, and usually show slow progression to generalized dystonia. Some patients may lose ambulation. A subset of patients may also have neurocognitive impairment, including mild intellectual disability or psychiatric manifestations (summary by Steel et al., 2020). In a review of the pathogenesis of disorders with prominent dystonia, Monfrini et al. (2021) classified DYT30 as belonging to a group of neurologic disorders termed 'HOPS-associated neurologic disorders' (HOPSANDs), which are caused by mutations in genes encoding various components of the autophagic/endolysosomal system, including VPS16. [from OMIM]

Clinical features

From HPO
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Bipolar affective disorder
MedGen UID:
2649
Concept ID:
C0005586
Mental or Behavioral Dysfunction
Bipolar disorder is an illness of mood characterized by alternating episodes of elevated and depressed moods, which are interspersed with euthymic periods.
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.
Impulsivity
MedGen UID:
43850
Concept ID:
C0021125
Mental or Behavioral Dysfunction
Acting on the spur of the moment or on a momentary basis without consideration of outcomes; having difficulty establishing or following plans; experiencing a sense of urgency and engaging in behavior that is uninhibited, cannot be inhibited, and is uncontrolled. The possibility of repression is inconceivable.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Intellectual disability, moderate
MedGen UID:
7680
Concept ID:
C0026351
Mental or Behavioral Dysfunction
Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.
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.
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).
Writer cramp
MedGen UID:
57821
Concept ID:
C0154676
Disease or Syndrome
A focal dystonia of the fingers, hand, and/or forearm that appears when the affected person attempts to do a task that requires fine motor movements such as writing or playing a musical instrument.
Hamartoma of hypothalamus
MedGen UID:
137970
Concept ID:
C0342418
Finding
Pallister-Hall-like syndrome (PHLS) is a pleiotropic autosomal recessive disorder characterized by phenotypic variability. Patients exhibit postaxial polydactyly as well as hypothalamic hamartoma, cardiac and skeletal anomalies, and craniofacial dysmorphisms. Hirschsprung disease has also been observed (Rubino et al., 2018; Le et al., 2020). Pallister-Hall syndrome (146510) is an autosomal dominant disorder with features overlapping those of PHLS, caused by mutation in the GLI3 gene (165240).
Diffuse cerebral atrophy
MedGen UID:
108958
Concept ID:
C0598275
Finding
Diffuse unlocalised atrophy affecting the cerebrum.
Compulsive behaviors
MedGen UID:
109373
Concept ID:
C0600104
Mental or Behavioral Dysfunction
Behavior that consists of repetitive acts, characterized by the feeling that one "has to" perform them, while being aware that these acts are not in line with one's overall goal.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Oromandibular dystonia
MedGen UID:
473560
Concept ID:
C2242577
Sign or Symptom
A kind of focal dystonia characterized by forceful contractions of the face, jaw, and/or tongue causing difficulty in opening and closing the mouth and often affecting chewing and speech.
Leg dystonia
MedGen UID:
1671070
Concept ID:
C4732775
Sign or Symptom
A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the legs.
Arm dystonia
MedGen UID:
1671069
Concept ID:
C4732776
Finding
A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the arms.
Globus pallidus hypointensity on susceptibility-weighted imaging
MedGen UID:
1747154
Concept ID:
C5421571
Finding
Hypointence (dark) appearance of the globus pallidus inmagnetic resonance imaging using susceptibility weighted imaging (SWI).

Professional guidelines

PubMed

Jankovic J, Carruthers J, Naumann M, Ogilvie P, Boodhoo T, Attar M, Gupta S, Singh R, Soliman J, Yushmanova I, Brin MF, Shen J
Toxins (Basel) 2023 May 17;15(5) doi: 10.3390/toxins15050342. PMID: 37235376Free PMC Article
Kaplan SL, Coulter C, Sargent B
Pediatr Phys Ther 2018 Oct;30(4):240-290. doi: 10.1097/PEP.0000000000000544. PMID: 30277962Free PMC Article
Heidenreich E, Johnson R, Sargent B
Pediatr Phys Ther 2018 Jul;30(3):164-175. doi: 10.1097/PEP.0000000000000517. PMID: 29924060Free PMC Article

Recent clinical studies

Etiology

Boy N, Mühlhausen C, Maier EM, Ballhausen D, Baumgartner MR, Beblo S, Burgard P, Chapman KA, Dobbelaere D, Heringer-Seifert J, Fleissner S, Grohmann-Held K, Hahn G, Harting I, Hoffmann GF, Jochum F, Karall D, Konstantopoulous V, Krawinkel MB, Lindner M, Märtner EMC, Nuoffer JM, Okun JG, Plecko B, Posset R, Sahm K, Scholl-Bürgi S, Thimm E, Walter M, Williams M, Vom Dahl S, Ziagaki A, Zschocke J, Kölker S
J Inherit Metab Dis 2023 May;46(3):482-519. Epub 2022 Nov 17 doi: 10.1002/jimd.12566. PMID: 36221165
Cif L, Demailly D, Lin JP, Barwick KE, Sa M, Abela L, Malhotra S, Chong WK, Steel D, Sanchis-Juan A, Ngoh A, Trump N, Meyer E, Vasques X, Rankin J, Allain MW, Applegate CD, Attaripour Isfahani S, Baleine J, Balint B, Bassetti JA, Baple EL, Bhatia KP, Blanchet C, Burglen L, Cambonie G, Seng EC, Bastaraud SC, Cyprien F, Coubes C, d'Hardemare V; Deciphering Developmental Disorders Study, Doja A, Dorison N, Doummar D, Dy-Hollins ME, Farrelly E, Fitzpatrick DR, Fearon C, Fieg EL, Fogel BL, Forman EB, Fox RG; Genomics England Research Consortium, Gahl WA, Galosi S, Gonzalez V, Graves TD, Gregory A, Hallett M, Hasegawa H, Hayflick SJ, Hamosh A, Hully M, Jansen S, Jeong SY, Krier JB, Krystal S, Kumar KR, Laurencin C, Lee H, Lesca G, François LL, Lynch T, Mahant N, Martinez-Agosto JA, Milesi C, Mills KA, Mondain M, Morales-Briceno H; NIHR BioResource, Ostergaard JR, Pal S, Pallais JC, Pavillard F, Perrigault PF, Petersen AK, Polo G, Poulen G, Rinne T, Roujeau T, Rogers C, Roubertie A, Sahagian M, Schaefer E, Selim L, Selway R, Sharma N, Signer R, Soldatos AG, Stevenson DA, Stewart F, Tchan M; Undiagnosed Diseases Network, Verma IC, de Vries BBA, Wilson JL, Wong DA, Zaitoun R, Zhen D, Znaczko A, Dale RC, de Gusmão CM, Friedman J, Fung VSC, King MD, Mohammad SS, Rohena L, Waugh JL, Toro C, Raymond FL, Topf M, Coubes P, Gorman KM, Kurian MA
Brain 2020 Dec 5;143(11):3242-3261. doi: 10.1093/brain/awaa304. PMID: 33150406Free PMC Article
Latorre A, Rocchi L, Bhatia KP
Exp Brain Res 2020 Aug;238(7-8):1685-1692. Epub 2020 Jul 25 doi: 10.1007/s00221-020-05863-2. PMID: 32712678
Heidenreich E, Johnson R, Sargent B
Pediatr Phys Ther 2018 Jul;30(3):164-175. doi: 10.1097/PEP.0000000000000517. PMID: 29924060Free PMC Article
Dressler D
Handb Clin Neurol 2011;100:513-38. doi: 10.1016/B978-0-444-52014-2.00038-0. PMID: 21496605

Diagnosis

Boy N, Mühlhausen C, Maier EM, Ballhausen D, Baumgartner MR, Beblo S, Burgard P, Chapman KA, Dobbelaere D, Heringer-Seifert J, Fleissner S, Grohmann-Held K, Hahn G, Harting I, Hoffmann GF, Jochum F, Karall D, Konstantopoulous V, Krawinkel MB, Lindner M, Märtner EMC, Nuoffer JM, Okun JG, Plecko B, Posset R, Sahm K, Scholl-Bürgi S, Thimm E, Walter M, Williams M, Vom Dahl S, Ziagaki A, Zschocke J, Kölker S
J Inherit Metab Dis 2023 May;46(3):482-519. Epub 2022 Nov 17 doi: 10.1002/jimd.12566. PMID: 36221165
Huang L, Fu C, Xiong F, He C, Wei Q
Cell Transplant 2021 Jan-Dec;30:963689721989266. doi: 10.1177/0963689721989266. PMID: 33559479Free PMC Article
Tyślerowicz M, Kiedrzyńska W, Adamkiewicz B, Jost WH, Sławek J
Neurol Neurochir Pol 2020;54(3):232-242. Epub 2020 Apr 14 doi: 10.5603/PJNNS.a2020.0021. PMID: 32285434
Heidenreich E, Johnson R, Sargent B
Pediatr Phys Ther 2018 Jul;30(3):164-175. doi: 10.1097/PEP.0000000000000517. PMID: 29924060Free PMC Article
Rubin SE, Wagner RS
Surv Ophthalmol 1986 May-Jun;30(6):366-76. doi: 10.1016/0039-6257(86)90090-1. PMID: 3523807

Therapy

Albright AL
Childs Nerv Syst 2023 Oct;39(10):2877-2886. Epub 2023 Jul 6 doi: 10.1007/s00381-023-06045-5. PMID: 37410128
Jankovic J, Carruthers J, Naumann M, Ogilvie P, Boodhoo T, Attar M, Gupta S, Singh R, Soliman J, Yushmanova I, Brin MF, Shen J
Toxins (Basel) 2023 May 17;15(5) doi: 10.3390/toxins15050342. PMID: 37235376Free PMC Article
Tyślerowicz M, Kiedrzyńska W, Adamkiewicz B, Jost WH, Sławek J
Neurol Neurochir Pol 2020;54(3):232-242. Epub 2020 Apr 14 doi: 10.5603/PJNNS.a2020.0021. PMID: 32285434
Shetty AS, Bhatia KP, Lang AE
Neurobiol Dis 2019 Dec;132:104462. Epub 2019 May 9 doi: 10.1016/j.nbd.2019.05.001. PMID: 31078682
Boelig RC, Barton SJ, Saccone G, Kelly AJ, Edwards SJ, Berghella V
J Matern Fetal Neonatal Med 2018 Sep;31(18):2492-2505. Epub 2017 Jul 11 doi: 10.1080/14767058.2017.1342805. PMID: 28614956

Prognosis

Kaplan SL, Coulter C, Sargent B
Pediatr Phys Ther 2018 Oct;30(4):240-290. doi: 10.1097/PEP.0000000000000544. PMID: 30277962Free PMC Article
Heidenreich E, Johnson R, Sargent B
Pediatr Phys Ther 2018 Jul;30(3):164-175. doi: 10.1097/PEP.0000000000000517. PMID: 29924060Free PMC Article
Graus F, Dalmau J
Curr Opin Neurol 2012 Dec;25(6):795-801. doi: 10.1097/WCO.0b013e328359da15. PMID: 23041955Free PMC Article
Bonifati V
Parkinsonism Relat Disord 2012 Jan;18 Suppl 1:S4-6. doi: 10.1016/S1353-8020(11)70004-9. PMID: 22166450
Wijemanne S, Jankovic J
Neurology 2007 Oct 16;69(16):1585-94. doi: 10.1212/01.wnl.0000277699.48155.39. PMID: 17938368

Clinical prediction guides

Garg K, Samala R, Agrawal M, Rajan R, Singh M
Neurol India 2020 Nov-Dec;68(Supplement):S322-S324. doi: 10.4103/0028-3886.302460. PMID: 33318369
Cif L, Demailly D, Lin JP, Barwick KE, Sa M, Abela L, Malhotra S, Chong WK, Steel D, Sanchis-Juan A, Ngoh A, Trump N, Meyer E, Vasques X, Rankin J, Allain MW, Applegate CD, Attaripour Isfahani S, Baleine J, Balint B, Bassetti JA, Baple EL, Bhatia KP, Blanchet C, Burglen L, Cambonie G, Seng EC, Bastaraud SC, Cyprien F, Coubes C, d'Hardemare V; Deciphering Developmental Disorders Study, Doja A, Dorison N, Doummar D, Dy-Hollins ME, Farrelly E, Fitzpatrick DR, Fearon C, Fieg EL, Fogel BL, Forman EB, Fox RG; Genomics England Research Consortium, Gahl WA, Galosi S, Gonzalez V, Graves TD, Gregory A, Hallett M, Hasegawa H, Hayflick SJ, Hamosh A, Hully M, Jansen S, Jeong SY, Krier JB, Krystal S, Kumar KR, Laurencin C, Lee H, Lesca G, François LL, Lynch T, Mahant N, Martinez-Agosto JA, Milesi C, Mills KA, Mondain M, Morales-Briceno H; NIHR BioResource, Ostergaard JR, Pal S, Pallais JC, Pavillard F, Perrigault PF, Petersen AK, Polo G, Poulen G, Rinne T, Roujeau T, Rogers C, Roubertie A, Sahagian M, Schaefer E, Selim L, Selway R, Sharma N, Signer R, Soldatos AG, Stevenson DA, Stewart F, Tchan M; Undiagnosed Diseases Network, Verma IC, de Vries BBA, Wilson JL, Wong DA, Zaitoun R, Zhen D, Znaczko A, Dale RC, de Gusmão CM, Friedman J, Fung VSC, King MD, Mohammad SS, Rohena L, Waugh JL, Toro C, Raymond FL, Topf M, Coubes P, Gorman KM, Kurian MA
Brain 2020 Dec 5;143(11):3242-3261. doi: 10.1093/brain/awaa304. PMID: 33150406Free PMC Article
Boelig RC, Barton SJ, Saccone G, Kelly AJ, Edwards SJ, Berghella V
J Matern Fetal Neonatal Med 2018 Sep;31(18):2492-2505. Epub 2017 Jul 11 doi: 10.1080/14767058.2017.1342805. PMID: 28614956
Graus F, Dalmau J
Curr Opin Neurol 2012 Dec;25(6):795-801. doi: 10.1097/WCO.0b013e328359da15. PMID: 23041955Free PMC Article
Borg M
Neurophysiol Clin 2006 Sep-Dec;36(5-6):309-18. Epub 2007 Jan 17 doi: 10.1016/j.neucli.2006.12.006. PMID: 17336775

Recent systematic reviews

Dai S, Chen H, Luo T
BMC Pregnancy Childbirth 2023 Oct 28;23(1):761. doi: 10.1186/s12884-023-06059-6. PMID: 37898733Free PMC Article
Boelig RC, Barton SJ, Saccone G, Kelly AJ, Edwards SJ, Berghella V
J Matern Fetal Neonatal Med 2018 Sep;31(18):2492-2505. Epub 2017 Jul 11 doi: 10.1080/14767058.2017.1342805. PMID: 28614956
Moro E, LeReun C, Krauss JK, Albanese A, Lin JP, Walleser Autiero S, Brionne TC, Vidailhet M
Eur J Neurol 2017 Apr;24(4):552-560. Epub 2017 Feb 10 doi: 10.1111/ene.13255. PMID: 28186378Free PMC Article
Smit M, Bartels AL, van Faassen M, Kuiper A, Niezen-Koning KE, Kema IP, Dierckx RA, de Koning TJ, Tijssen MA
Neurosci Biobehav Rev 2016 Jun;65:264-75. Epub 2016 Apr 9 doi: 10.1016/j.neubiorev.2016.03.015. PMID: 27073048
Colosimo C, Tiple D, Berardelli A
Neurotox Res 2012 Nov;22(4):265-73. Epub 2012 Feb 23 doi: 10.1007/s12640-012-9314-y. PMID: 22359151

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