History

The most common presenting symptom of dopamine-responsive dystonia (DRD) is a gait disturbance. These patients may be misdiagnosed as having cerebral palsy.

Typically, the dystonia starts in 1 lower limb (with evening exacerbation), resulting in a tiptoe (equinus) walking pattern. Early in the disease course, patients are symptom free in the morning. Diurnal aggravation of symptoms depends more on the number of waking hours than on physical activity.

The disease progresses markedly in the first 15 years, with postural dystonia progressing to all 4 limbs (even in the morning) by the end of the second decade. Progression slows in the third decade and plateaus thereafter.^[22]

Variations in DRD clinical presentation have been described. These include trunk and focal dystonias, such as spasmodic torticollis, oromandibular dystonia, and writer's cramp.^{[5, 23, 24]}

Clinical features described here are those characterized for dominant DRD with GCH1 gene mutations. Some of the TH-deficient patients have predominant parkinsonism features without diurnal fluctuations.^{[17, 25, 26]}

The onset and clinical severity of disease are variable, sometimes even within a single family, due to putative gender effects on allele penetrance.^[27]

Physical Examination

The patient may have stunted growth with short stature if the disease was not treated in childhood. This improves if treatment is started early in the disease course. The dystonia is variable in severity, depending on the duration of disease prior to treatment.

Gait disturbance is characterized by leg stiffness and a tendency to walk in an equinus posture. The great toe is dorsiflexed. Gait tends to worsen later in the day. With increasing age and without treatment, dystonia spreads to involve the trunk and all 4 extremities.

Postural tremor, which is not observed in childhood, appears after the third decade. Resting tremor and rigidity are absent, and interlimb coordination is preserved (even in advanced cases).

Bradykinesia may develop. This is not due to failure of initiation and poverty of movement as in parkinsonism; rather, it is due to failure of reciprocal innervation resulting from the dystonia.^[28]

Muscle tone is increased and deep tendon reflexes are exaggerated (with ankle clonus). The plantar reflex is flexor, although striatal toe is common.^[22]

Clinical manifestations have significant heterogeneity, with intrafamilial variation in clinical phenotype, including the degree of levodopa responsiveness.^[29]

Differential Diagnoses

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