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Dystonia 32(DYT32)

MedGen UID:
1794239
Concept ID:
C5562029
Disease or Syndrome
Synonyms: DYSTONIA 32; DYT32
 
Gene (location): VPS11 (11q23.3)
 
Monarch Initiative: MONDO:0030486
OMIM®: 619637

Definition

Dystonia-32 (DYT32) is an autosomal recessive neurologic disorder characterized by sustained or intermittent muscle contractions causing abnormal movements or posturing. The onset of symptoms is in adulthood, and the disorder is slowly progressive with eventual generalized involvement of the limbs, trunk, neck, and larynx, resulting in dysarthria and dysphagia. Brain imaging may show abnormalities in the basal ganglia. There are no additional neurologic signs or symptoms (summary by Monfrini et al., 2021). In a review of the pathogenesis of disorders with prominent dystonia, Monfrini et al. (2021) classified DYT32 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 VPS11. [from OMIM]

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
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.
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).
Limb dystonia
MedGen UID:
152944
Concept ID:
C0751093
Sign or Symptom
A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the limbs.
Lower limb hyperreflexia
MedGen UID:
322973
Concept ID:
C1836696
Finding
Laryngeal dystonia
MedGen UID:
409603
Concept ID:
C1963946
Disease or Syndrome
A form of focal dystonia that affects the vocal cords, associated with involuntary contractions of the vocal cords causing interruptions of speech and affecting the voice quality and often leading to patterned, repeated breaks in speech.
T2 hypointense basal ganglia
MedGen UID:
868349
Concept ID:
C4022743
Finding
A darker than expected T2 signal on magnetic resonance imaging (MRI) of the basal ganglia. This term refers to a diffuse hypointensity affecting all of the basal ganglia.
Brain atrophy
MedGen UID:
1643639
Concept ID:
C4551584
Disease or Syndrome
Partial or complete wasting (loss) of brain tissue that was once present.

Professional guidelines

PubMed

Yoshida K
Clin Oral Investig 2019 Jan;23(1):405-411. Epub 2018 May 2 doi: 10.1007/s00784-018-2449-3. PMID: 29717363
Pirio Richardson S, Wegele AR, Skipper B, Deligtisch A, Jinnah HA; Dystonia Coalition Investigators
Neurology 2017 Feb 7;88(6):543-550. Epub 2017 Jan 11 doi: 10.1212/WNL.0000000000003596. PMID: 28077492Free PMC Article

Recent clinical studies

Etiology

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
Kulkarni DP, Kamath VD, Stewart JT
Dysphagia 2017 Aug;32(4):467-471. Epub 2017 Apr 26 doi: 10.1007/s00455-017-9802-6. PMID: 28447217
Defazio G, Hallett M, Jinnah HA, Conte A, Berardelli A
Mov Disord 2017 Apr;32(4):498-509. Epub 2017 Feb 10 doi: 10.1002/mds.26934. PMID: 28186662Free PMC Article
Hartung B, Sampson S, Leucht S
Cochrane Database Syst Rev 2015 Mar 6;2015(3):CD003443. doi: 10.1002/14651858.CD003443.pub3. PMID: 25749632Free PMC Article
Carenzio G, Carlisi E, Morani I, Tinelli C, Barak M, Bejor M, Dalla Toffola E
Eur J Phys Rehabil Med 2015 Oct;51(5):539-45. Epub 2015 Feb 18 PMID: 25692687

Diagnosis

Alvarez-Mora MI, Rodríguez-Revenga L, Jodar M, Potrony M, Sanchez A, Badenas C, Oriola J, Villanueva-Cañas JL, Muñoz E, Valldeoriola F, Cámara A, Compta Y, Carreño M, Martí MJ, Sánchez-Valle R, Madrigal I
Genes (Basel) 2023 Mar 28;14(4) doi: 10.3390/genes14040813. PMID: 37107571Free PMC Article
Abboud H, Probasco JC, Irani S, Ances B, Benavides DR, Bradshaw M, Christo PP, Dale RC, Fernandez-Fournier M, Flanagan EP, Gadoth A, George P, Grebenciucova E, Jammoul A, Lee ST, Li Y, Matiello M, Morse AM, Rae-Grant A, Rojas G, Rossman I, Schmitt S, Venkatesan A, Vernino S, Pittock SJ, Titulaer MJ; Autoimmune Encephalitis Alliance Clinicians Network
J Neurol Neurosurg Psychiatry 2021 Jul;92(7):757-768. Epub 2021 Mar 1 doi: 10.1136/jnnp-2020-325300. PMID: 33649022Free PMC Article
Edinoff A, Wu N, deBoisblanc C, Feltner CO, Norder M, Tzoneva V, Kaye AM, Cornett EM, Kaye AD, Viswanath O, Urits I
Psychopharmacol Bull 2020 Sep 14;50(4):32-59. PMID: 33012872Free PMC Article
Marsico P, Frontzek-Weps V, Balzer J, van Hedel HJ
J Child Neurol 2017 Jan;32(1):132-138. Epub 2016 Oct 15 doi: 10.1177/0883073816671681. PMID: 27742862
Haque S, Bilal Shafi BB, Kaleem M
Radiographics 2012 Mar-Apr;32(2):557-71. doi: 10.1148/rg.322105143. PMID: 22411949

Therapy

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
Abboud H, Probasco JC, Irani S, Ances B, Benavides DR, Bradshaw M, Christo PP, Dale RC, Fernandez-Fournier M, Flanagan EP, Gadoth A, George P, Grebenciucova E, Jammoul A, Lee ST, Li Y, Matiello M, Morse AM, Rae-Grant A, Rojas G, Rossman I, Schmitt S, Venkatesan A, Vernino S, Pittock SJ, Titulaer MJ; Autoimmune Encephalitis Alliance Clinicians Network
J Neurol Neurosurg Psychiatry 2021 Jul;92(7):757-768. Epub 2021 Mar 1 doi: 10.1136/jnnp-2020-325300. PMID: 33649022Free PMC Article
Edinoff A, Wu N, deBoisblanc C, Feltner CO, Norder M, Tzoneva V, Kaye AM, Cornett EM, Kaye AD, Viswanath O, Urits I
Psychopharmacol Bull 2020 Sep 14;50(4):32-59. PMID: 33012872Free PMC Article
Kulkarni DP, Kamath VD, Stewart JT
Dysphagia 2017 Aug;32(4):467-471. Epub 2017 Apr 26 doi: 10.1007/s00455-017-9802-6. PMID: 28447217
Scaglione F
Toxins (Basel) 2016 Mar 4;8(3) doi: 10.3390/toxins8030065. PMID: 26959061Free PMC Article

Prognosis

Lipman AR, Fan X, Shen Y, Chung WK
Clin Genet 2022 Oct;102(4):288-295. Epub 2022 Jun 26 doi: 10.1111/cge.14180. PMID: 35722745Free PMC Article
Himmelreich N, Blau N, Thöny B
Mol Genet Metab 2021 Jun;133(2):123-136. Epub 2021 Apr 19 doi: 10.1016/j.ymgme.2021.04.003. PMID: 33903016
Vetro A, Nielsen HN, Holm R, Hevner RF, Parrini E, Powis Z, Møller RS, Bellan C, Simonati A, Lesca G, Helbig KL, Palmer EE, Mei D, Ballardini E, Van Haeringen A, Syrbe S, Leuzzi V, Cioni G, Curry CJ, Costain G, Santucci M, Chong K, Mancini GMS, Clayton-Smith J, Bigoni S, Scheffer IE, Dobyns WB, Vilsen B, Guerrini R; ATP1A2/A3-collaborators
Brain 2021 Jun 22;144(5):1435-1450. doi: 10.1093/brain/awab052. PMID: 33880529
Khosravani S, Chen G, Ozelius LJ, Simonyan K
Neurobiol Dis 2021 Jan;148:105223. Epub 2020 Dec 11 doi: 10.1016/j.nbd.2020.105223. PMID: 33316367Free PMC Article
Herr T, Hummel T, Vollmer M, Willert C, Veit B, Gamain J, Fleischmann R, Lehnert B, Mueller JU, Stenner A, Kronenbuerger M
J Neural Transm (Vienna) 2020 Mar;127(3):347-354. Epub 2020 Feb 15 doi: 10.1007/s00702-020-02156-4. PMID: 32062706Free PMC Article

Clinical prediction guides

Kaiyrzhanov R, Rad A, Lin SJ, Bertoli-Avella A, Kallemeijn WW, Godwin A, Zaki MS, Huang K, Lau T, Petree C, Efthymiou S, Karimiani EG, Hempel M, Normand EA, Rudnik-Schöneborn S, Schatz UA, Baggelaar MP, Ilyas M, Sultan T, Alvi JR, Ganieva M, Fowler B, Aanicai R, Tayfun GA, Al Saman A, Alswaid A, Amiri N, Asilova N, Shotelersuk V, Yeetong P, Azam M, Babaei M, Monajemi GB, Mohammadi P, Samie S, Banu SH, Pinto Basto J, Kortüm F, Bauer M, Bauer P, Beetz C, Garshasbi M, Issa AH, Eyaid W, Ahmed H, Hashemi N, Hassanpour K, Herman I, Ibrohimov S, Abdul-Majeed BA, Imdad M, Isrofilov M, Kaiyal Q, Khan S, Kirmse B, Koster J, Lourenço CM, Mitani T, Moldovan O, Murphy D, Najafi M, Pehlivan D, Rocha ME, Salpietro V, Schmidts M, Shalata A, Mahroum M, Talbeya JK, Taylor RW, Vazquez D, Vetro A, Waterham HR, Zaman M, Schrader TA, Chung WK, Guerrini R, Lupski JR, Gleeson J, Suri M, Jamshidi Y, Bhatia KP, Vona B, Schrader M, Severino M, Guille M, Tate EW, Varshney GK, Houlden H, Maroofian R
Brain 2024 Apr 4;147(4):1436-1456. doi: 10.1093/brain/awad380. PMID: 37951597Free PMC Article
Lipman AR, Fan X, Shen Y, Chung WK
Clin Genet 2022 Oct;102(4):288-295. Epub 2022 Jun 26 doi: 10.1111/cge.14180. PMID: 35722745Free PMC Article
Vetro A, Nielsen HN, Holm R, Hevner RF, Parrini E, Powis Z, Møller RS, Bellan C, Simonati A, Lesca G, Helbig KL, Palmer EE, Mei D, Ballardini E, Van Haeringen A, Syrbe S, Leuzzi V, Cioni G, Curry CJ, Costain G, Santucci M, Chong K, Mancini GMS, Clayton-Smith J, Bigoni S, Scheffer IE, Dobyns WB, Vilsen B, Guerrini R; ATP1A2/A3-collaborators
Brain 2021 Jun 22;144(5):1435-1450. doi: 10.1093/brain/awab052. PMID: 33880529
Edinoff A, Wu N, deBoisblanc C, Feltner CO, Norder M, Tzoneva V, Kaye AM, Cornett EM, Kaye AD, Viswanath O, Urits I
Psychopharmacol Bull 2020 Sep 14;50(4):32-59. PMID: 33012872Free PMC Article
Marsico P, Frontzek-Weps V, Balzer J, van Hedel HJ
J Child Neurol 2017 Jan;32(1):132-138. Epub 2016 Oct 15 doi: 10.1177/0883073816671681. PMID: 27742862

Recent systematic reviews

Decraene B, Smeets S, Remans D, Ortibus E, Vandenberghe W, Nuttin B, Theys T, De Vloo P
Neuromodulation 2024 Apr;27(3):440-446. Epub 2023 Nov 24 doi: 10.1016/j.neurom.2023.10.187. PMID: 37999699
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
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
Hartung B, Sampson S, Leucht S
Cochrane Database Syst Rev 2015 Mar 6;2015(3):CD003443. doi: 10.1002/14651858.CD003443.pub3. PMID: 25749632Free PMC Article
Steeves TD, Day L, Dykeman J, Jette N, Pringsheim T
Mov Disord 2012 Dec;27(14):1789-96. Epub 2012 Oct 31 doi: 10.1002/mds.25244. PMID: 23114997

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