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Torsion dystonia 4(DYT4)

MedGen UID:: 342124
•Concept ID:: C1851943
•: Disease or Syndrome

Synonyms:	Autosomal dominant torsion dystonia 4; Dystonia musculorum deformans 4; Hereditary whispering dysphonia
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. Autosomal dominant inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	TUBB4A (19p13.3)

Monarch Initiative:	MONDO:0007493
OMIM®:	128101
Orphanet:	ORPHA98805

Definition

Dystonia-4, also known as whispering dysphonia, is an autosomal dominant neurologic disorder characterized by onset in the second to third decade of progressive laryngeal dysphonia followed by the involvement of other muscles, such as the neck or limbs. Some patients develop an ataxic gait (summary by Hersheson et al., 2013). [from OMIM]

Clinical features

From HPO

Slender build

MedGen UID:: 376828
•Concept ID:: C1850573
•: Finding

Asthenic habitus refers to a slender build with long limbs, an angular profile, and prominent muscles or bones.

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Dysphagia

MedGen UID:: 41440
•Concept ID:: C0011168
•: Disease or Syndrome

Difficulty in swallowing.

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Torsion dystonia

MedGen UID:: 3941
•Concept ID:: C0013423
•: Disease or Syndrome

Sustained involuntary muscle contractions that produce twisting and repetitive movements of the body.

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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).

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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.

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Gait ataxia

MedGen UID:: 155642
•Concept ID:: C0751837
•: Sign or Symptom

A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.

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Generalized dystonia

MedGen UID:: 341342
•Concept ID:: C1848954
•: Finding

A type of dystonia that affects all or most of the body.

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Hemidystonia

MedGen UID:: 743329
•Concept ID:: C1960561
•: Disease or Syndrome

Hemidystonia refers to dystonia which involves the ipsilateral face, arm, and leg.

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Dysphonia

MedGen UID:: 282893
•Concept ID:: C1527344
•: Mental or Behavioral Dysfunction

Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause.

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Narrow face

MedGen UID:: 373334
•Concept ID:: C1837463
•: Finding

Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).

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Sunken cheeks

MedGen UID:: 869726
•Concept ID:: C4024154
•: Finding

Lack or loss of the soft tissues between the zygomata and mandible.

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Abnormality of head or neck
- Narrow face
- Sunken cheeks
Abnormality of the digestive system
- Dysphagia
Abnormality of the nervous system
Abnormality of the voice
- Dysphonia
Growth abnormality
- Slender build

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVTorsion dystonia 4

Focal, segmental or multifocal dystonia
- Torsion dystonia 4

Follow this link to review classifications for Torsion dystonia 4 in Orphanet.

Professional guidelines

PubMed

In vivo optogenetic inhibition of striatal parvalbumin-reactive interneurons induced genotype-specific changes in neuronal activity without dystonic signs in male DYT1 knock-in mice.

Schulz A, Richter F, Richter A
J Neurosci Res 2023 Apr;101(4):448-463. Epub 2022 Dec 22 doi: 10.1002/jnr.25157. PMID: 36546658

Sporadic adult onset primary torsion dystonia is a genetic disorder by the temporal discrimination test.

Kimmich O, Bradley D, Whelan R, Mulrooney N, Reilly RB, Hutchinson S, O'Riordan S, Hutchinson M
Brain 2011 Sep;134(Pt 9):2656-63. Epub 2011 Aug 11 doi: 10.1093/brain/awr194. PMID: 21840890

Treatment of cervical dystonia: a comparison of measures for outcome assessment.

Lindeboom R, Brans JW, Aramideh M, Speelman HD, De Haan RJ
Mov Disord 1998 Jul;13(4):706-12. doi: 10.1002/mds.870130417. PMID: 9686779

See all (4)

Recent clinical studies

Etiology

X-Linked Dystonia-Parkinsonism ("Lubag") May Present with Peripheral Synucleinopathy.

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

Pallidal degenerations and related disorders: an update.

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

Voice and swallowing dysfunction in X-linked dystonia parkinsonism.

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

Long-term follow-up of deep brain stimulation for Meige syndrome.

Lyons MK, Birch BD, Hillman RA, Boucher OK, Evidente VG
Neurosurg Focus 2010 Aug;29(2):E5. doi: 10.3171/2010.4.FOCUS1067. PMID: 20672922

Genetics of primary torsion dystonia.

Brüggemann N, Klein C
Curr Neurol Neurosci Rep 2010 May;10(3):199-206. doi: 10.1007/s11910-010-0107-5. PMID: 20425035

See all (53)

Diagnosis

X-Linked Dystonia-Parkinsonism ("Lubag") May Present with Peripheral Synucleinopathy.

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

Pallidal degenerations and related disorders: an update.

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

Genetics of primary torsion dystonia.

Brüggemann N, Klein C
Curr Neurol Neurosci Rep 2010 May;10(3):199-206. doi: 10.1007/s11910-010-0107-5. PMID: 20425035

Dystonia.

Bressman SB
Curr Opin Neurol 1998 Aug;11(4):363-72. doi: 10.1097/00019052-199808000-00013. PMID: 9725083

Sleep and degenerative neurologic disorders.

Chokroverty S
Neurol Clin 1996 Nov;14(4):807-26. doi: 10.1016/s0733-8619(05)70286-3. PMID: 8923496

See all (46)

Therapy

A Network Imaging Biomarker of X-Linked Dystonia-Parkinsonism.

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

4-Phenylbutyrate attenuates the ER stress response and cyclic AMP accumulation in DYT1 dystonia cell models.

Cho JA, Zhang X, Miller GM, Lencer WI, Nery FC
PLoS One 2014;9(11):e110086. Epub 2014 Nov 7 doi: 10.1371/journal.pone.0110086. PMID: 25379658 Free PMC Article

Dystonia.

Bressman SB
Curr Opin Neurol 1998 Aug;11(4):363-72. doi: 10.1097/00019052-199808000-00013. PMID: 9725083

Torsion dystonia.

Berardelli A, Currà A, Manfredi M
Curr Opin Neurol 1996 Aug;9(4):317-20. doi: 10.1097/00019052-199608000-00014. PMID: 8858192

Lisuride in dystonia.

Quinn NP, Lang AE, Sheehy MP, Marsden CD
Neurology 1985 May;35(5):766-9. doi: 10.1212/wnl.35.5.766. PMID: 3887215

See all (34)

Prognosis

Basal ganglia and cerebellar pathology in X-linked dystonia-parkinsonism.

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

Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene.

Lohmann K, Wilcox RA, Winkler S, Ramirez A, Rakovic A, Park JS, Arns B, Lohnau T, Groen J, Kasten M, Brüggemann N, Hagenah J, Schmidt A, Kaiser FJ, Kumar KR, Zschiedrich K, Alvarez-Fischer D, Altenmüller E, Ferbert A, Lang AE, Münchau A, Kostic V, Simonyan K, Agzarian M, Ozelius LJ, Langeveld AP, Sue CM, Tijssen MA, Klein C
Ann Neurol 2013 Apr;73(4):537-45. Epub 2013 Apr 17 doi: 10.1002/ana.23829. PMID: 23595291 Free PMC Article

Long-term follow-up of deep brain stimulation for Meige syndrome.

Lyons MK, Birch BD, Hillman RA, Boucher OK, Evidente VG
Neurosurg Focus 2010 Aug;29(2):E5. doi: 10.3171/2010.4.FOCUS1067. PMID: 20672922

Genetics of primary torsion dystonia.

Brüggemann N, Klein C
Curr Neurol Neurosci Rep 2010 May;10(3):199-206. doi: 10.1007/s11910-010-0107-5. PMID: 20425035

The relationship between trauma and idiopathic torsion dystonia.

Fletcher NA, Harding AE, Marsden CD
J Neurol Neurosurg Psychiatry 1991 Aug;54(8):713-7. doi: 10.1136/jnnp.54.8.713. PMID: 1940944 Free PMC Article

See all (29)

Clinical prediction guides

A Network Imaging Biomarker of X-Linked Dystonia-Parkinsonism.

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

Neuropathology and morphometry of dentate nucleus neurons in DYT1 brains: Cerebellar abnormalities in isolated dystonia.

Iacono D, Peng H, Rabin ML, Kurlan R
J Neuropathol Exp Neurol 2023 Jul 20;82(8):695-706. doi: 10.1093/jnen/nlad044. PMID: 37352388

DYT-TUBB4A (DYT4 Dystonia): New Clinical and Genetic Observations.

Bally JF, Camargos S, Oliveira Dos Santos C, Kern DS, Lee T, Pereira da Silva-Junior F, Puga RD, Cardoso F, Barbosa ER, Yadav R, Ozelius LJ, de Carvalho Aguiar P, Lang AE
Neurology 2021 Apr 6;96(14):e1887-e1897. Epub 2020 Sep 17 doi: 10.1212/WNL.0000000000010882. PMID: 32943487 Free PMC Article

Voice and swallowing dysfunction in X-linked dystonia parkinsonism.

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

Dystonia-4 (DYT4)-associated TUBB4A mutants exhibit disorganized microtubule networks and inhibit neuronal process growth.

Watanabe N, Itakaoka M, Seki Y, Morimoto T, Homma K, Miyamoto Y, Yamauchi J
Biochem Biophys Res Commun 2018 Jan 1;495(1):346-352. Epub 2017 Nov 7 doi: 10.1016/j.bbrc.2017.11.038. PMID: 29127012

See all (45)

Recent systematic reviews

Understanding Psychiatric Disorders in Idiopathic and Inherited (Monogenic) Forms of Isolated and Combined Dystonia: A Systematic Review.

Lane V, Lane M, Sturrock A, Rickards H
J Neuropsychiatry Clin Neurosci 2021 Fall;33(4):295-306. Epub 2021 Jul 19 doi: 10.1176/appi.neuropsych.20110293. PMID: 34280321

See all (1)

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Torsion dystonia 4(DYT4)

Definition

Clinical features

Term Hierarchy

Professional guidelines

PubMed

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Recent systematic reviews

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Practice guidelines

Molecular resources

Consumer resources

Reviews

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