• Test code: 03351
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Dystonia Comprehensive Panel

Test description

The Invitae Dystonia Panel analyzes up to 23 genes associated with the dystonias, a group of movement disorders characterized by sustained muscle contractions that lead to abnormal postures and repetitive movements. These genes were curated based on available evidence to provide a comprehensive test for the monogenic causes of dystonia, including both isolated and combined dystonias.

Dystonias are a heterogeneous group of disorders. Identification of the molecular basis of disease can be useful in confirming a diagnosis, predicting disease course, and informing recurrence risk.

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Primary panel (18 genes)


Add-on Preliminary-evidence Genes for Dystonia (5 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


Alternative tests to consider

In some cases, dystonia may have overlapping features with Parkinson disease or related conditions involving parkinsonian features. In these cases, clinicians may consider the Invitae Hereditary Parkinsonism Panel.

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions that cause abnormal and often repetitive movements and/or postures. Dystonic movements are typically patterned and twisting and may be tremulous. Dystonia is often initiated or worsened by voluntary action and is associated with overflow muscle activation.

Several criteria are used to classify and ultimately diagnose the subtypes of dystonia. Isolated dystonia (formerly referred to as primary dystonia) refers to subtypes in which dystonia and tremor are the only motor features present. Combined dystonia (formerly referred to as dystonia plus) includes subtypes that have another movement disorder, such as parkinsonism, in addition to dystonia. Distribution of symptoms is also a key to classification. Clinically affected areas of the body include the upper or lower cranial region, the cervical region, the larynx, the trunk, and the upper or lower limbs. Focal dystonia affects only one region of the body while segmental dystonia affects two or more contiguous regions. Multifocal dystonia affects two or more non-contiguous regions and generalized dystonia affects the trunk and two or more other areas. Finally, hemidystonia refers to a preponderance of symptoms limited to one side of the body. Occurrence of symptoms may also vary with the time of day. Dystonia may be persistent, diurnal, action-specific, or paroxysmal.

GeneSubtypeInheritanceAdditional information
Autosomal dominantAutosomal recessive
Isolated dystonia
ANO3 DYT24 Focal, segmental, cervical dystonia; 2% of dystonia (PMID: 23200863)
CIZ1* DYT23 Focal, cervical dystonia
GNAL DYT25 Adult onset, focal, segmental, cervical dystonia
HPCA* DYT2 Early onset, cervical and progressively generalized dystonia (PMID: 25799108)
THAP1 DYT6 Adolescent onset, generalized, segmental; 25% of individuals with early onset and positive family history (PMID: 19345147)
TOR1A DYT1 Early onset, generalized, rarely focal; 60% of early onset isolated dystonia (90% in Ashkenazi Jewish populations)
TUBB4A DYT4 Isolated and combined dystonia
Combined dystonia
ATP1A3 DYT12 + parkinsonism
ATP7B Wilson disease
DRD2* DYT11 + myoclonus
GCH1 DYT5a + parkinsonism, dopa-responsive
HEXA Hexosaminidase A deficiency
KCTD17* DYT26 + myoclonus
PRKN (formerly known as PARK2) Early-onset Parkinson disease
PNKD DYT8 Paroxysmal nonkinesigenic dyskinesia
PRKRA DYT16 + parkinsonism
PRRT2 DYT10 Episodic kinesigenic dyskinesia
SGCE DYT11 + myoclonus
SLC2A1 DYT9, DYT18 Paroxysmal choreoathetosis and progressive spastic paraplegia [DYT9]; paroxysmal exercise-induced dyskinesia and epilepsy [DYT18]
SLC6A3 Parkinsonism-dystonia, infantile
SPR DYT5b + parkinsonism; dopa-responsive; sepiapterin reductase deficiency
TH DYT5b + parkinsonism; dopa-responsive; tyrosine hydroxylase deficiency
TOR1AIP1* + cerebellar atrophy, cardiomyopathy

*Preliminary-evidence gene

This panel includes all the common genetic causes of dystonia. The most common forms of hereditary isolated dystonia are caused by mutations in the TOR1A (DYT1) and THAP1 (DYT6) genes. Pathogenic variants in TOR1A account for 60% of cases of early-onset generalized isolated dystonia in the general population and 90% of cases in the Ashkenazi Jewish population. This panel also includes other genes that have been identified as causes of isolated and combined dystonias, although the exact contribution of these genes to the overall detection rate is not known and is dependent on an individual’s clinical presentation.

Dystonia is most often inherited in an autosomal dominant pattern, including the forms associated with ANO3, ATP1A3, CIZ1, DRD2, GCH1, GNAL, KCTD17, PNKD, PRRT2, SGCE, SLC2A1, THAP1, TOR1A, and TUBB4A. The only gene known to be associated with an autosomal recessive form of isolated dystonia is HPCA. PRKN, PRKRA, SLC6A3, SPR, TH and TOR1AIP1 are associated with autosomal recessive forms of combined dystonia.

Several subtypes of dystonia demonstrate incomplete penetrance. The penetrance of mutations in TOR1A and THAP1 is markedly reduced. Only 30% of individuals with a pathogenic variant in TOR1A will develop symptoms, while approximately 60% of individuals with a pathogenic variant in THAP1 will develop symptoms. Other forms that demonstrate reduced penetrance include GCH1 and ATP1A3, as well as SGCE, which demonstrates reduced penetrance and maternal imprinting. Expressivity may vary even within families.

Overall, isolated dystonia occurs in an estimated 16 of 100,000 individuals. TOR1A-related dystonia, the most common form of early-onset isolated dystonia, has a prevalence ranging from 1 in 20,000 among Ashkenazi Jews to 1 in 200,000 in the general population. Late-onset isolated dystonia is typically sporadic and has an estimated prevalence of 30 in 100,000. No estimates exist for the prevalence of the other dystonia subtypes.

The clinical spectrum of dystonias is broad. Genetic testing can confirm the suspected clinical diagnosis or rule out disorders with a similar clinical presentation. A confirmed genetic diagnosis may help predict disease prognosis and progression, facilitate early detection of symptoms, inform family planning and carrier screening, or promote enrollment in clinical trials.

Diagnostic testing is important as the list of treatable dystonias continues to grow. In the case of dopa-responsive dystonias, administration of levodopa can produce excellent and sustained responses.

  1. Charlesworth, G, et al. Mutations in HPCA cause autosomal-recessive primary isolated dystonia. Am. J. Hum. Genet. 2015; 96(4):657-65. PMID: 25799108
  2. Lohmann, K, Klein, C. Genetics of dystonia: what's known? What's new? What's next?. Mov. Disord. 2013; 28(7):899-905. doi: 10.1002/mds.25536. PMID: 23893446
  3. Jinnah, HA, et al. Recent developments in dystonia. Curr. Opin. Neurol. 2015; 28(4):400-5. PMID: 26110799
  4. Wijemanne, S, Jankovic, J. Dopa-responsive dystonia--clinical and genetic heterogeneity. Nat Rev Neurol. 2015; 11(7):414-24. doi: 10.1038/nrneurol.2015.86. PMID: 26100751
  5. Steeves, TD, et al. The prevalence of primary dystonia: a systematic review and meta-analysis. Mov. Disord. 2012; 27(14):1789-96. doi: 10.1002/mds.25244. PMID: 23114997
  6. Petrucci, S, Valente, EM. Genetic issues in the diagnosis of dystonias. Front Neurol. 2013; 4:34. doi: 10.3389/fneur.2013.00034. PMID: 23596437
  7. Muller, U. The monogenic primary dystonias. Brain. 2009; 132(Pt 8):2005-25. doi: 10.1093/brain/awp172. PMID: 19578124
  8. Albanese, A, et al. Phenomenology and classification of dystonia: a consensus update. Mov. Disord. 2013; 28(7):863-73. doi: 10.1002/mds.25475. PMID: 23649720
  9. Phukan, J, et al. Primary dystonia and dystonia-plus syndromes: clinical characteristics, diagnosis, and pathogenesis. Lancet Neurol. 2011; 10(12):1074-85. doi: 10.1016/S1474-4422(11)70232-0. PMID: 22030388
  10. Klein, C, et al. Dystonia Overview. 2003 Oct 28 (Update 2003 Oct 28). In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1155/ PMID: 20301334
  11. Bressman, SB, et al. Mutations in THAP1 (DYT6) in early-onset dystonia: a genetic screening study. Lancet Neurol. 2009; 8(5):441-6. doi: 10.1016/S1474-4422(09)70081-X. PMID: 19345147
  12. Klein, C. Genetics in dystonia. Parkinsonism Relat. Disord. 2014; 20 Suppl 1:S137-42. doi: 10.1016/S1353-8020(13)70033-6. PMID: 24262166
  13. Balint, B, Bhatia, KP. Isolated and combined dystonia syndromes - an update on new genes and their phenotypes. Eur. J. Neurol. 2015; 22(4):610-7. doi: 10.1111/ene.12650. PMID: 25643588
  14. Charlesworth, G, et al. Mutations in ANO3 cause dominant craniocervical dystonia: ion channel implicated in pathogenesis. Am. J. Hum. Genet. 2012; 91(6):1041-50. doi: 10.1016/j.ajhg.2012.10.024. PMID: 23200863

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ANO3 NM_031418.2
ATP1A3 NM_152296.4
ATP7B NM_000053.3
CIZ1 NM_012127.2
DRD2 NM_000795.3
GCH1 NM_000161.2
GNAL NM_001142339.2
HEXA NM_000520.4
HPCA NM_002143.2
KCTD17 NM_001282684.1
PNKD NM_015488.4
PRKN NM_004562.2
PRKRA NM_003690.4
PRRT2 NM_145239.2
SGCE NM_003919.2
SLC2A1 NM_006516.2
SLC6A3 NM_001044.4
SPR NM_003124.4
TH NM_199292.2
THAP1 NM_018105.2
TOR1A NM_000113.2
TOR1AIP1 NM_001267578.1
TUBB4A NM_006087.3