Although DYT1 mutations account for the majority of inherited cases of generalized dystonia, they are also implicated in a small proportion of the more restricted dystonias, particularly blepharospasm (see further on). Some individuals in families affected with generalized dystonia will demonstrate only localized forms (e.g., writer’s cramp or torticollis). The general rule stated above still holds, namely, that the inherited variety (dystonia musculorum deformans) related to DYT1 manifests early in life and begins in one limb and then spreads to most muscles of the body, while in the common dystonias (mostly sporadic but some heritable) the disease remains confined to the craniocervical or another region, does not generalize, and has an adult onset.
Clinical features The first manifestations of the generalized disease may be rather subtle. Intermittently, and usually after activity (late in the day), the patient (usually a child between 6 and 14 years of age, less often an adolescent) begins to invert one foot, to extend one leg and foot in an unnatural way, or to hunch one shoulder, raising the question of a nervous tic. As time passes, the motor disturbance becomes more persistent and interferes increasingly with the patient’s activities. Soon the muscles of the spine and shoulder or pelvic girdle become implicated in involuntary spasmodic twisting movements. The cardinal feature of these severe dystonic muscle contractions is the simultaneous contraction of both agonists and antagonists at a joint. These cocontraction spasms are intermittent at first; in intervals that are free of the dystonia, muscular tone and volitional movements are normal. In some instances, the muscles are hypotonic. Gradually, the spasms become more frequent; finally, they are continuous and the body may become grotesquely contorted, as shown in Fig. 4-5A. Lateral and rotatory scoliosis uniformly results as secondary deformities. For a time, recumbency relieves the spasms, but later on position has no influence. The hands are seldom involved, although at times they may be held in a fisted posture. Cranial muscles do not escape, and in a few instances a slurring, staccato-type speech was the initial manifestation. Uncontrollable blepharospasm was the initial disorder in one of our patients; in two others, severe dysarthria and dysphagia were the first signs, caused by dystonia of the tongue, pharyngeal, and laryngeal muscles.
Other manifestations include torticollis, tortipelvis, dromedary gait, propulsive gait, action tremor, myoclonic jerks during voluntary movement, and mild choreoathetosis of the limbs. Excitement worsens the dystonia and sleep abolishes it. As the years pass the postural distortion may become fixed to the point where it does not disappear even in sleep. Tendon reflexes are normal, corticospinal signs are absent, and there is no ataxia, sensory abnormality, convulsive disorder, or dementia.