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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Author

Nirjal K Nikhar, MD, FRCP Private Practice

Nirjal K Nikhar, MD, FRCP is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Coauthor(s)

Haresh Mani, MD Assistant Professor, Department of Pathology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Disclosure: Nothing to disclose.

Syed M S Ahmed, MD Neurologist and Sleep Specialist, Capital Neurology and Sleep Medicine; Staff Attending in Neurology and Sleep Medicine, Montgomery General Hospital; Staff Attending in Neurology and Sleep Medicine, Suburban Hospital

Syed M S Ahmed, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, Maryland State Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock (managed by a financial services company) in healthcare companies including Allergan, Cellectar Biosciences, CVS Health, Danaher Corp, Johnson & Johnson.

Acknowledgements

Nestor Galvez-Jimenez, MD, MSc, MHA Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society

Disclosure: Nothing to disclose.

Ann M Neumeyer, MD Clinic Director, Instructor, Departments of Neurology and Pediatrics, Massachusetts General Hospital, Harvard Medical School

Ann M Neumeyer, MD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

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