Dystonia may be an inherited condition caused by genetic mutations. It can also result from exposure to certain drugs, birth injuries, strokes, or as a symptom of other neurological disorders. For many patients, however, the cause remains unknown. There are two main categories of causes of dystonia: primary and secondary (or non-primary).
Primary dystonia is a condition in which dystonia is the only clinical feature. There is no evidence of cell death or a known cause. It is also known as idiopathic torsion dystonia. Primary dystonia is thought to have greater genetic contribution, even in the absence of a family history of dystonia. Several mutations have been identified in genes that are responsible for many cases of primary dystonia. The two most common and important genes associated with primary dystonia are DYT1 and DYT6. Most genetic forms of dystonia start with symptoms in childhood or adolescence. The DYT1 gene regulates the production of the torsinA protein. Mutations in this gene are associated with most cases of early-onset limb-onset primary dystonia and it is most common in individuals of North European Ashkenazi Jewish descent. The DYT6 gene was initially described in Mennonite families with generalized dystonia. This gene codes for the THAP1 protein. Mutations of this gene are associated with childhood and adult onset dystonia, usually affecting limbs and cervical and cranial muscles. Both DYT1 and DYT6 forms of dystonia tend to progress initially to involve multiple body regions. How mutations in these genes lead to dystonia is not yet well understood. Commercial tests are available to determine if these genes are affected in individuals. However, for the majority of people living with primary dystonia, the cause remains unknown.
- Myoclonus Dystonia, characterized by variable combinations of dystonia and myoclonus (marked, rapid, lightning-like muscle movements), with onset in childhood or adolescence. Myoclonus is often the most prominent feature, and tends to occur or worsen with voluntary movement. Its course is relatively benign with stabilization of symptoms after a few years. It is a hereditary condition and has been associated with mutations in the epsilon sarcoglycan gene (SCGE).
- Dopa-responsive Dystonia (DRD) is a genetic disorder of childhood onset. It affects girls more commonly than boys. Children affected by DRD had onset of dystonia affecting usually the legs initially and many may have features of parkinsonism or exaggerated reflex responses. The symptoms generally become more severe as the day progresses and are worse at night. Their symptoms dramatically and characteristically improve with low-dose levodopa, and amino acid that is a precursor of the neurotransmitter dopamine. It has been associated with mutations in the guanosine triphosphate (GTP) cyclohydrolase I (GHC1 or DYT5) gene.
- Rapid-onset Dystonia Parkinsonism (RDP) is a rare inherited disorder with onset in childhood or adulthood. It is characterized by sudden development over hours, days or weeks of a combination of dystonia and parkinsonism. The symptoms may in some cases develop after certain stressful events. Affected individuals may have abnormally low levels of homovanillic acid (HVA) in their spinal fluid. It has been linked to mutations in the ATP1A3 gene.
- Wilson’s Disease is a rare genetic disorder of copper metabolism, in which copper accumulates first in the liver, and eventually in other organs, including the brain. Its neurological manifestations may include dystonia, parkinsonism and tremor.
- Huntington’s Disease, also known as Huntington’s chorea is a hereditary progressive neurodegenerative disorder that results in behavioral and psychiatric abnormalities, cognitive decline and abnormal movements. While chorea is the most common involuntary movement in this condition (rapid irregular random jerky movements that may affect face, arm, legs or trunk), dystonia and parkinsonism may also be present.
- Spinocerebellar Ataxias are a group of progressive degenerative inherited conditions characterized by slowly progressive incoordination of hands, speech, eye movements and gait (called ataxia, from Greek “not ordered”). Onset may be at any age. Other symptoms may include frequently dystonia. Frequently, atrophy of the cerebellum occurs.
- Methymalonic Aciduria is an inherited disorder of metabolism. Neurological symptoms typically manifest during the first years of life and include generalize dystonia, difficulty swallowing and speaking and different degrees of paralysis.
- Parkinson’s disease caused by Parkin mutations. Among the several genes that are known to cause PD (accounting nonetheless for a small minority of patients), one of the most important is a gene called Parkin. This gene creates a protein that helps break down proteins inside brain cells, and when mutated, this function is impaired, leading to neuronal death. PD patients with Parkin mutations present very similarly to sporadic or non-genetic PD, but those patients tend to have a younger onset of disease (less than 40) and to have prominent foot, hand and neck dystonia as symptoms.
- Paroxysmal dystonia (also called paroxysmal dyskinesias) are neurological conditions characterized by discreet and sudden episodes of involuntary movements that may include dystonia or faster randomly irregular movements (chorea) and flailing movements of a limb (ballismus). The abnormal movements appear in a sudden and unpredictable manner with rapid return to normal function. They are classified based on precipitating factors into paroxysmal kinesigenic dyskinesia (PKD) and paroxysmal non-kinesigenic dyskinesia (PNKD). In PKD, the abnormal movements are provoked by sudden voluntary movement or startle. In PNKD, the attacks may occur spontaneously or be triggered by alcohol or caffeine. Genetic abnormalities have been recently linked to these conditions.
Age of onset
The age at onset is an important indicator of whether the dystonia is more likely to spread to other body regions. Early onset dystonia refers to dystonia that develops before age 21. The younger the patient at dystonia onset, the higher the likelihood that the dystonia may involve other areas. Late-onset dystonia begins after age 21. In patients with primary late-onset dystonia, the dystonia often begins in the upper body, such as the neck, head, neck, or an arm. Regions of the body Generalized Dystonia: is the most widespread form of dystonia; it affects the legs or one leg and the trunk, plus other regions, most commonly the arms. Focal Dystonia: involves only one region of the body, such as the neck, vocal cords or hand. Hemidystonia: affects one half of the body. Segmental Dystonia: affects two or more adjacent body regions, such as the neck and an arm. Multifocal Dystonia: affects two or more distant regions of the body, such as the upper face and the hand.