Dystonia is characterized by sustained or intermittent muscular contractions that lead to abnormal postures and movements, often repetitive. Symptoms of dystonia may appear from early childhood to late adulthood, affecting one (focal), several (multifocal, segmental), or numerous parts of the body (generalized). Generalized dystonia usually includes adolescent-onset progressive and incapacitating disorders with a known genetic basis. The group of primary focal dystonia generally appears in adults and usually involves the neck, face, or arms; the number of known genes is lower, although up to 25% of cases tend to have a positive family history (Steeves et al., 2012). It is worth noting that dystonias are diseases with great phenotypic and genotypic heterogeneity, often with incomplete penetrance even within the same family (Albanese et al., 2013).
A prevalence of approximately 16/100 000 individuals is estimated (Steeves et al., 2012).
Although numerous risk factors have been described by association studies, the diagnostic-genetic approach is aimed at performing diagnoses with a clinical application for the patient.
For this, four phenotype groups have been established:
- Primary dystonia (isolated, focal, or generalized, as the main symptom): 8-gene core panel, with the particularly relevant genes TOR1A (DYT1), THAP1 (DYT6), and GNAL (DYT25, adult-onset craniocervical dystonia).
- Dopa-responsive dystonia (Segawa syndrome): 3-gene specific panel (GCH1, TH, and SPR).
- Myoclonus-dystonia: 3-gene specific panel (SGCE [DYT11], whose yield is up to 50% in familial cases, and TOR1A or [DYT1] and KCTD17, which are included as differential diagnoses).
- Combined dystonia — dystonia-plus — or complex dystonia phenotypes: 24-gene extended panel for a more comprehensive etiologic approach and for complex cases.