Diagnostic Considerations

If dystonia clinically manifests with another syndrome complex, consider the following differential diagnoses:

Parkinsonism -Dopamine-responsive dystonia, juvenile Parkinson disease, Huntington disease, X-linked dystonia parkinsonism, rapid-onset dystonia parkinsonism, dystonic lipidoses, Hallervorden-Spatz disease, corticobasal ganglionic degeneration, basal ganglia calcification, progressive supranuclear palsy, Parkinson disease, Machado-Joseph disease (SCA, type 3), Wilson disease, gangliosidoses, neuroacanthocytosis
Neuropathy - Metachromatic leukodystrophy, acanthocytosis, SCA types 2 and 3, GM2 gangliosidosis
Ataxia - Ataxia-telangiectasia, neuronal ceroid lipofuscinosis, metachromatic leukodystrophy, Hartnup disease
Optic and/or retinal conditions - GM2 gangliosidosis, Hallervorden-Spatz disease, metachromatic leukodystrophy
Oculomotor findings - Dystonic lipidoses, SCA types 1-3, ataxia-telangiectasia, corticobasal ganglionic degeneration, progressive supranuclear palsy, Huntington disease
Tics -Neuroacanthocytosis

Differential Diagnoses

Workup

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Media Gallery

Idiopathic torsion dystonia. Major nuclear complex of the basal ganglia is the striatum, which is composed of the caudate and putamen. The striatum receives glutamatergic input from the cerebral cortex and dopaminergic input from the substantia nigra pars compacta (SNc). Two types of spiny projection neurons receive cortical and nigral inputs: those that project directly and those that project indirectly to the internal segment of the globus pallidus (GPI), which is the major output site of the basal ganglia. Complementary action of both of these pathways regulates the overall function of the GPI. The GPI, which, in turn, provides tonic inhibitory (ie, gamma-aminobutyric acid [GABA]–ergic) discharges downstream into the thalamic nuclei that project to the frontal cortical and other CNS areas. Direct pathway (D1) inhibits the substantia nigra pars reticulata (SNr) and the GPI, which are the major output sites, resulting in a net disinhibition and facilitation of thalamocortical circuits. Indirect pathway (D2), through serial connections with the globus pallidus pars externa (GPe) and the subthalamic nucleus (STN), is excitatory to the GPI, resulting in further inhibitory action on thalamocortical pathways. In this model, the mean discharge rate of the GPI is the key factor that determines a hypokinetic or hyperkinetic movement disorder. Increased inhibitory influences of the GPI on the thalamocortical circuitry result in hypokinetic disorders, such as Parkinson disease, whereas decreased GPI activity results in hyperkinetic disorders, such as hemiballismus. VL = ventrolateral thalamus.

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Table 1. Anatomic Distribution of Primary Torsion Dystonia

Focal	Body Site
Segmental	two or more contiguous body regions
Multifocal	two or more noncontiguous body regions
Generalized	involving atleast one leg, the trunk and another body region
Hemidystonia	involving one side of the body

Table.

Type	Designation	Mode of Inheritance	Gene	Gene Locus	OMIM#
DYT1	Early-onset generalized	Autosomal dominant	TOR1A	9q.34.11	128100
DYT2	Early-onset generalized	Autosomal recessive	Uknown	Uknown	224500
DYT3	X-linked dystonia parkinsonism (Lubag syndrome)	X-chromosomal recessive	TAF1	Xq13.1	314250
DYT4	Torsion dystonia (Whispering dysphonia)	Autosomal dominant	TUBB4A	19p13.3	128101
DYT5a	Dopa-responsive dystonia (Segawa disease)	Autosomal dominant	GCH1	14q22.1–22.2	128230
DYT5b	Dopa-responsive dystonia	Autosomal recessive	TH	11p15.5	605407
DYT6	Adolescent-onset mixed phenotype	Autosomal dominant	THAP1	8p11.21	602629
DYT7	Paroxysmal dystonic choreoathetosis	Autosomal dominant	Unknown	18p	602124
DYT8	Paroxysmal kinesigenic, nonkinesigenic dyskinesia	Autosomal dominant	MR-1	2q33–35	118800
DYT9	Paroxysmal choreoathetosis with spasticity	Autosomal dominant	CSE	1p	601042
DYT10	Paroxysmal kinesigenic dystonia	Autosomal dominant	PRRT2	16q11.2–12.1	128200
DYT11	Myoclonus dystonia	Autosomal dominant	SGCE	7q21.3	159900
DYT11	Myoclonus dystonia	Autosomal dominant	DRD2	11q23.2	159900
DYT12	Rapid-onset dystonia parkinsonism (syndrome)	Autosomal dominant	ATP1A3	19q12–13.2	128235
DYT13	Early- and late-onset focal or craniocervical dystonia	Autosomal dominant	Unknown	1p36.32-p36.13	607671
DYT14	Dopa-responsive generalized dystonia
DYT15	Myoclonus-dystonia	Autosomal dominant	Unknown	18p11	607488
DYT16	Dystonia-parkinsonism syndrome	Autosomal recessive	PRKRA	2q31.2	612067
DYT17	Adolescent onset	Autosomal recessive	Unknown	20p11.2-q13.12	612406
DYT18	Paroxysmal exertion-induced dyskinesia	Autosomal dominant	SLC2A1	1p34.2	612126
DYT19	Paroxysmal kinesigenic dyskinesia 2	Autosomal dominant	Unknown	16q13-q22.1	611031
DYT20	Paroxysmal nonkinesigenic dyskinesia 2	Autosomal dominant	Unknown	2q31	611147
DYT21	Late-onset torsion dystonia	Autosomal dominant	Unknown	2q14.3-q21.3	614588
DYT22			Unknown	Unknown	Not listed
DYT23	Adult-onset cervical dystonia	Autosomal dominant	CIZ1	9q34	614860
DYT24	Focal dystonia	Autosomal dominant	ANO3	11p14.2	615034
DYT25	Adult-onset focal dystonia	Autosomal dominant	GNAL	18p11.21	615073

Table.

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Author

Priyantha Herath, MD, PhD Director of Movement Disorders Clinic, Attenting Neurologist, Department of Neurology, University of South Carolina School of Medicine at Columbia

Priyantha Herath, MD, PhD is a member of the following medical societies: American Academy of Neurology, International Parkinson and Movement Disorder Society

Disclosure: Nothing to disclose.

Coauthor(s)

Sonal Mehta, MD Clinical Assistant Professor, Department of Neurology, University of South Carolina School of Medicine

Sonal Mehta, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Stroke Association, Neurocritical Care Society, Society of Vascular and Interventional Neurology

Disclosure: Nothing to disclose.

Souvik Sen, MD, MPH, MS, FAHA Professor and Chair, Department of Neurology, University of South Carolina School of Medicine

Souvik Sen, MD, MPH, MS, FAHA is a member of the following medical societies: American Academy of Neurology, Association for Patient-Oriented Research, American Heart Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nestor Galvez-Jimenez, MD, MSc, MHA The Pauline M Braathen Endowed Chair in Neurology, Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, International Parkinson and Movement Disorder Society

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Alliance, Bioserenity, Ceribell, Eisai, Greenwich, LivaNova, Neurelis, Neuropace, Nexus, RSC, SK life science, Sunovion<br/>Serve(d) as a speaker or a member of a speakers bureau for: Alliance, Aquestive, Bioserenity, Eisai, Greenwich, LivaNova, Neurelis, SK life science, Sunovion<br/>Received research grant from: Cerevel, LivaNova, Greenwich, SK biopharmaceuticals, Takeda.

Additional Contributors

Stephen T Gancher, MD Adjunct Associate Professor, Department of Neurology, Oregon Health Sciences University

Stephen T Gancher, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, International Parkinson and Movement Disorder Society

Disclosure: Nothing to disclose.

Jasvinder Chawla, MD, MBA Chief of Neurology, Hines Veterans Affairs Hospital; Professor of Neurology, Loyola University Medical Center

Jasvinder Chawla, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Medical Association

Disclosure: Nothing to disclose.

Vijaya K Patil, MD Assistant Professor, Department of Neurology, Edward Hines Jr Veterans Affairs Medical Center, Loyola University, Chicago Stritch School of Medicine

Vijaya K Patil, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Medical Council of India

Disclosure: Nothing to disclose.

Sections Torsion Dystonias
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