Idiopathic isolated dystonia is manifested by spasms and dystonic postures without being associated, except for tremor, with other neurological symptoms such as ataxia, muscle weakness, seizures or cognitive impairment. The cause is unknown, except for genetic causes identified in some cases. It is not associated with degenerative neuropathological lesions. There is a bimodal distribution of age of onset, with age peaks at 9 years (early-onset isolated dystonia) and 45 years (late-onset or adult dystonia). There is a relationship between the age of onset, the body region initially affected and the progression of the disease. Early-onset dystonia affects one leg in the initial stages and then generalizes to involve the trunk. It is usually hereditary. Adult dystonia, usually sporadic, starts in one arm or in the cervical or cranial musculature and rarely generalizes.
Isolated early-onset dystonia
It is included in a heterogeneous group of disorders which, in most cases, show an autosomal dominant pattern of inheritance. Several studies have shown that even many apparently sporadic cases are hereditary in cause, particularly in Jewish patients of Ashkenazi descent. The most common form is autosomal dominant early-onset dystonia associated with mutations in the DYT1 gene at locus 9q34 that encodes a protein called torsin A. The role of torsin A plays in the development of dystonia. The role of torsin A in the development of dystonia is still unknown.
It usually begins in the leg or arm and rarely in the neck or vocal cords. In most patients the disease progresses and in about half of them the disease generalizes to the upper and lower extremities. The disease progresses more rapidly in patients in whom symptoms begin in one leg. Initial symptoms typically consist of abnormal walking (action) movements that disappear with rest. They often disappear with running or walking backwards. Later, spasms arise when the patient performs any other leg movement and eventually are present even with the limb at rest.
If the disease begins in an arm, symptoms usually appear when performing a motor act with the limb, sometimes highly specific, such as writing, sewing or painting. Later on, dystonic movements occur, even when another part of the body performs a voluntary movement or with less specific limb activities, to eventually be present even at rest.
As a consequence of the frequent involvement of the trunk and legs, gait is disturbed in many patients. When attempting to walk, the leg performs rotational movements or a hip abduction movement occurs. The foot adopts equinovarus or eversion postures. The trunk flexes excessively in some patients, to give rise to a “dromedary” gait with the neck extended and the legs flexed at the hips. In some cases, walking is impossible and there is trunk involvement even at rest, which explains the term deforming muscular dystonia by which this disease has been referred to until recently.
In DYT1 dystonia, the maximum degree of disability is usually reached in the first few years, after which the disease tends to remain static or may even improve slightly. The dystonia rarely leads to the death of the patient who, even in the most severe cases, may have a normal longevity.
Two other early-onset clinical syndromes similar to DYT1 dystonia are DYT6 dystonia (autosomal dominant, penetrance 60%; mutations in the THAPI gene and with significant laryngeal involvement) and DYT13 dystonia (only described in a few families and with initial cervical involvement 73%; in arms 27%, relatively benign course). Isolated early-onset autosomal recessive dystonia have been recently described.
Isolated adult-onset dystonia
The clinical manifestations differ considerably from those of the child. The onset is in the cranial or upper extremity musculature and the dystonia does not generalize. Most cases are considered sporadic. The most frequently encountered focal dystonia in adults are blepharospasm, oromandibular dystonia, spasmodic torticollis, laryngeal dystonia (spasmodic dysphonia) and arm dystonia (scribe cramp).
The role of heredity in adult dystonia is less clear than in childhood dystonia. In 20% of cases there is an affected relative. In one family with adult dystonia (cervical and laryngeal) a locus on chromosome 18p has been defined (DYT7 dystonia). Sex-linked recessive forms of dystonia in which the gene has been mapped to the pericentromeric region of the X chromosome have been described in natives of the Philippines. Recently, isolated adult dystonia-causing mutations have been described in three new genes: ANO3 (DYT24), GNAL (DYT25) and CIZ1 (DYT23), with cranio-cervical involvement and prominent tremor. Other factors probably play an important role in some adult focal dystonia. Thus, local trauma can trigger focal dystonia in carriers of the primary dystonia gene, and peripheral lesions preceding dystonic blepharospasm (e.g., recurrent conjunctivitis) or spasmodic torticollis (cervical trauma) have been described.