Dystonia is a syndrome of sustained muscle contractions of agonist and antagonist muscles, usually resulting in twisting, torsional, and repetitive movements or abnormal postures.
It can either be primary or secondary. Primary torsion dystonia (PTD) is dystonia in isolation without brain degeneration and without an acquired cause. Secondary dystonia includes a heterogenous group of etiologies including inherited (with and without brain degeneration) and acquired neurologic disorders. The phenotypic spectrum associated with PTD is broad, from early-onset generalized to adult-onset focal dystonia.
The first description of what is now considered primary, or idiopathic, torsion dystonia was described by Schwalbe in 1908. In 1911, Oppenheim termed this same condition dystonia musculorum deformans (DMD) or dysbasia lordotica progressiva.
Initially believed to be a manifestation of hysteria, idiopathic torsion dystonia is now established as a specific neurologic entity with a well-established genetic basis. DMD and Oppenheim disease are terms now used for childhood- and adolescent-onset dystonia due to the DYT1 gene.
Classification of dystonia
At the present time there are 25 types of genetically determined dystonias. Several classification schemes have been used to categorize the various forms of dystonia. One common scheme is based on genetic features, including mode of inheritance and molecular genetic data. There is also a topographic classification where torsion dystonia may be described as focal, segmental, multifocal, or generalized, depending on which anatomic distribution of the symptoms (see Table 1).
Table 1. Anatomic Distribution of Primary Torsion Dystonia (Open Table in a new window)
two or more contiguous body regions
two or more noncontiguous body regions
involving atleast one leg, the trunk and another body region
involving one side of the body
In addition, depending on the clinical features, dystonias can be divided into two main groups: isolated dystonia or combined dystonia. Combined dystonia can be classified into three sub-types: those accompanied by parkinsonism, by myoclonus, or by a mixed pattern of various hyperkinetic movements.
Genetically defined isolated dystonias include TOR1A/DYT1, TUBB4/DYT4, THAP1/DYT6, PRKRA/DYT16, CIZ1/DYT23, ANO3/DYT24, and GNAL/DYT25. Combined dystonias, accompanied by parkinsonism with known genetic loci include TAF1/DYT3, GCH1/DYT5a, TH/DYT5b, and ATP1A3/DYT12. Genetically determined dystonias that are accompanied by myoclonus include SGCE/DYT11, whereas dystonias that accompany a mixed pattern of hyperkinetic disorders include MR-1/DYT8, PRRT2/DYT10, and SLC2A1/ DYT18.
Sometimes, combined dystonias are also classified depending on whether the symptoms are continually and continuously present or whether they are paroxysmal. Generic forms of common, persistent combined dystonias are GCH1/ DYT5a, TH/DYT5b, SGCE/DYT11, APT1A3/DYT12, and TAF1/ DYT3. Genetically defined paroxysmal combined dystonias include MR-1/DYT8, PRRT2/DYT10, and SLC2A1/DYT18.
DYT1 (early-onset generalized dystonia)
DYT1 are caused by a 3-base pair in-frame deletion within the coding region of the TOR1A (torsinA) gene located on chromosome 9q34. TorsinA is expressed at high levels in neuronal cytoplasm of specific neuronal populations in the adult human brain, including the SN, thalamus, cerebellum, hippocampus, and neostriatum.
DYT1 is the most common hereditary dystonia. Phenomenologically, it is an isolated dystonia. Some degree of genetic anticipation in regards to the age of onset and disease severity has been noted in DYT1. It is especially common among the Ashkenazi Jewish population.
In most instances, DYT1 symptoms often start with a focal dystonia as talipes equinovarus of one leg in early childhood, typically around 6 years of age. The dystonic posturing then gradually progresses with age to other extremities and trunk muscles by the early teens. There is obvious asymmetry to the dystonia, with involvement of the extremities on the dominant side along with the ipsilateral sternocleidomastoid muscle. In these patients, interlimb coordination and locomotive movements are not affected at all. Moreover, intellectual, mental, and psychological functions are completely intact in these patients.
Based on clinical characteristics, DYT1 can be classified into two types: the postural type with appendicular and truncal dystonias, or the action type, which is associated with violent dyskinetic movements in addition to dystonic posture.
DYT5 (dopa-responsive dystonia)
Hereditary progressive dystonia with marked diurnal fluctuation, or Segawa disease, is an autosomal dominantly inherited dopa-responsive dystonia (DRD) caused by heterozygous mutations of the GCH1 gene located on chromosome 14q22.1-q22.2. DYT5 shows a marked female predominance in the young. In contrast, adult-onset cases show a male predominance
Onset is around 6 years of age, mostly with rigid talipes equinovarus of one foot not dissimilar to DYT1. With age, it expands to other limbs and trunk muscles by the midteens with progressive rigidity. Starting around age 10 years, postural tremor of 8 to 10 Hz appears. These symptoms show marked diurnal fluctuations, worsening through the day and almost absent in the early morning. However, this fluctuation decreases with age in the late teens, and is no longer apparent in early adulthood, when symptoms become static. Clinically, DYT5 is also classified into two types: postural and action. Patients with the action type develop dystonic movements of one extremity or the neck (action retrocollis) in addition to dystonic, and show focal or segmental dystonia during the teenage years.