Diagnostic Considerations
If dystonia clinically manifests with another syndrome complex, consider the following differential diagnoses:
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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
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Neuropathy - Metachromatic leukodystrophy, acanthocytosis, SCA types 2 and 3, GM2 gangliosidosis
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Ataxia - Ataxia-telangiectasia, neuronal ceroid lipofuscinosis, metachromatic leukodystrophy, Hartnup disease
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Optic and/or retinal conditions - GM2 gangliosidosis, Hallervorden-Spatz disease, metachromatic leukodystrophy
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Oculomotor findings - Dystonic lipidoses, SCA types 1-3, ataxia-telangiectasia, corticobasal ganglionic degeneration, progressive supranuclear palsy, Huntington disease
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Tics -Neuroacanthocytosis
Differential Diagnoses
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Parkinson Disease in Young Adults
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Post-Stroke Spasticity
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Psychogenic Dystonia
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Spinocerebellar Ataxia
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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.
Tables
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 |
| 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 |
