Generalized Dystonia

Generalized Dystonia

Dystonia is a neurological disorder characterized by uncontrollable muscle contractions resulting in involuntary postures. These postures can be accompanied by movements that are patterned and twisting and may resemble tremor. Generalized dystonia = refers to dystonia that is not limited to a single part of the body but affects multiple muscle groups throughout the body. Generalized dystonia typically affects muscles in the torso and limbs, and sometimes the neck and face. Patients have difficulty moving their bodies freely and controlling their body movements. It is important to note that dystonia does not target vital organs such as the heart. Generalized dystonia typically begins during childhood or adolescence, often without additional neurological symptoms. Initial symptoms may be a turned or twisted foot and/or leg. However, dystonia in children can be associated with more complex neurological or metabolic diagnoses. Generalized dystonia can occur with or without a family history. The symptoms may always be present or only occur in episodes.

Are there Different Types of Generalized Dystonia?

Early Onset Generalized Dystonia (DYT1/TOR1): DYT1 dystonia typically begins around age 10 years with the twisting of a foot or arm. Symptoms tend to progress to involve additional limbs and the torso, but usually not the face or neck. In rare cases, the vocal cord muscles are affected. The symptoms tend to be less severe the later in life they start and if they start in a hand or arm. About 30% of individuals who have the DYT1 genetic mutation will develop dystonia. If a person does not manifest symptoms before the age of 28 years, they will usually remain symptom-free for life—even if they have the DYT1 mutation. The DYT1 mutation is responsible for about 90% of early-onset generalized dystonia in individuals of Ashkenazi Jewish ancestry and up to about 50% of early-onset generalized dystonia in other ethnicities.

Adolescent-Onset Generalized Dystonia (DYT6/THAP): DYT6 may occur as generalized dystonia or remain focal to a specific part of the body. Although the symptoms may resemble DYT1 dystonia, the onset of DYT6 is usually in the late teens and symptoms are more likely to occur above the neck. Symptoms typically affect the muscles of the tongue, vocal cords, and face. Patients often have difficulty speaking. About 40% of individuals who have the mutation will develop dystonia. Testing for DYT1, DYT6, and other known dystonia genes is available. A genetic counselor can help families understand what genetic testing may be appropriate.

Symptoms

Symptoms of Generalized Dystonia can include:
• Twisted postures, for example in the torso or limbs
• Turning in of the foot or arm
• Muscle spasms, with or without pain
• Unusual walking with bending and twisting of the torso
• Rapid, sometimes rhythmic, jerking movements (often “myoclonic jerks”)
• Progression of symptoms leading to areas of the body remaining in sustained or fixed postures
Symptoms often begin in one area of the body and spread to other areas. Factors such as age and the part of the body where symptoms begin to play a significant role in the progression. The younger the age of onset, the more likely the dystonic symptoms will begin in one of the legs, spread upward to other areas, and possibly become generalized. However, if symptoms begin in the arm or neck, the progression to other body areas may be less likely. The age of onset varies, but the peak period is between the ages of seven and ten years with symptoms progressing, then stabilizing, within a five-year period.

Symptoms commonly begin with a specific action and are not present at rest. For example, if symptoms begin in one leg, they may only be present when walking and disappear when the individual runs or walks backward.

In generalized dystonia that begins in the arm, symptoms may be task-specific, i.e. apparent only during specific activities such as writing or playing a musical instrument. If the disorder progresses, the symptoms of arm dystonia may appear when another part of the body is engaged in the voluntary motor activity. If the dystonia spreads to involve parts of the body other than the limb of onset, it will first move to adjacent segments of the body and then outward to areas farther from the site where symptoms began.

Dystonia is usually present continually throughout the day whenever the affected body part is in use and may disappear with sleep.

Features such as cognition, strength, and the senses, including vision and hearing, are normal. While is a chronic disorder, it is not fatal.

Common Misdiagnoses

Generalized dystonia symptoms should not be confused with:
• Parkinson’s disease
• Tremor
• Cerebral palsy
• Orthopedic and structural conditions
• Behavioral disorders or mental illness

Cause

Most—but not all—people with early-onset generalized dystonia have a specific genetic mutation. The gene responsible for early-onset generalized dystonia, termed DYT1, was discovered in 1997. Early onset generalized dystonia of this kind may be referred to as DYT1 dystonia or Oppenheim’s dystonia. (Generalized forms of dystonia that occur in children with no mutation in the DYT1 gene may simply be called non-DYT1 early-onset generalized dystonia.)

The mode of inheritance for DYT1 dystonia is autosomal dominant. This means that a person only needs to inherit the mutation from one parent to develop symptoms. For reasons, scientists do not yet understand, approximately 30% of persons who inherit the DYT1 mutation will develop dystonia. This means that 70% of persons who inherit the abnormal gene never develop symptoms. If an individual inherits the DYT1 mutation but does not develop symptoms by age 30, symptoms may never develop. There is no way yet to predict whether a person with the abnormal gene will develop symptoms of the disorder. Also, the severity may differ markedly from person to person, including family members.

The DYT1 gene mutation may also be referred to as a “GAG deletion,” referring to the specific section of DNA that is missing. Exactly how the abnormal gene causes dystonia is presently unknown, and a major focus of research efforts.

For persons with early-onset generalized dystonia who do not have the DYT1 mutation, the cause is presumed to be primary, meaning that there is some genetic component that has yet to be identified. Secondary forms of generalized dystonia, such as dystonia secondary to cerebral palsy, may also begin in childhood.

Diagnosis

The diagnosis of early-onset generalized dystonia is not made by one definitive test, but rather primarily by information from the individual and the physical and neurological examination. In most cases, assorted laboratory tests are normal and used to rule out other disorders.

A genetic test is available to detect the DYT1 gene mutation to confirm a DYT1 dystonia diagnosis.

Treatment

Oral medications are often the mainstay of treatment for early-onset generalized dystonia, both DYT1 and non-DYT1 forms. Although there is no single drug that helps an overwhelming number of individuals, there are many that may be of benefit. These oral medications include levodopa, trihexyphenidyl, benztropine, diazepam, lorazepam, clonazepam, baclofen (oral and intrathecal—especially for dystonia and spasticity), carbamazepine, tetrabenazine (with lithium), and triple therapy such as a “cocktail” that includes tetrabenazine, fluphenazine, and trihexyphenidyl.

Botulinum toxin injections can be used to treat specific body parts that may be affected, such as the neck, jaw, hands, or feet.

Several surgical techniques may be appropriate for select individuals who do not respond to medications and botulinum toxin injections. These include ablative surgeries such as pallidotomy and thalamotomy, intrathecal baclofen, and deep brain stimulation.

Complementary therapies may be explored, particularly physical therapy, aquatic physical therapy, and regular relaxation techniques.