Case Reports

Indian Pediatrics 2001; 38: 1056-1058  

Dopa-Responsive Dystonia

Rajiv Mittal, Jatinder S. Goraya, Srikanta Basu

From the Department of Pediatrics, Government Medical College Hospital, Sector 32 B, Chandigarh 160 047, India.

Correspondence to: Dr. Jatinder S. Goraya, Reader, Department of Pediatrics, Government Medical College Hospital, Sector 32 B, Chandigarh 160 047, India.
E-mail: [email protected]

Manuscript received: November 7, 2000; Initial review completed: December 12, 2000; Revision accepted: January 30, 2001.

Dopa-responsive dystonia (DRD) also known as ‘hereditary progressive dystonia with diurnal variations’ or ‘Segawa’s syndrome’ was first described by Segawa et al. in 1976(1). The dystonia characteristically worsens throughout the day and there is marked benefit from sleep. Another equally important feature is the complete relief of symptoms from small doses of L-dopa(2). Because of lack of awareness, it is not unusual for this uncommon disorder to be mis-diagnosed as hysteria, hereditary spastic para-paresis or cerebral palsy(2-4). Since an effective therapy for DRD is available, implication of wrong diagnosis can be enor-mous. We report one such case to highlight these aspects.

Case Report

A 9-year-old girl presented with one year history of gait difficulties, toe-walking and frequent falls. The girl was born after a full-term normal vaginal delivery to non-consanguineous parents. The development was normal. Abnormal gait was noticed by the parents at the age of 8 years. Gradually, she developed instability of posture. She would walk with her eyes fixed on the ground. The symptoms used to worsen by evening and improve with sleep. These diurnal variations were observed for several days in the hospital also. There was no history of cognitive decline, developmental retardation/regression, behavi-oral problems, tremors or seizures. Family history was negative for any neurological or liver disease. General physical examination revealed a mentally normal girl with no pallor or icterus. There were no Kayser-Fleischer (KF) rings or hepatosplenomegaly. Central nervous system examination revealed normal tone and power. Deep tendon reflexes were normal. Plantar reflexes were however, bilaterally extensor. No sensory deficits were observed. Gait (examined when patient had been active for several hours) revealed toe-walking and hypertonia of tendoachillis. Investigations showed normal hemogram, liver and renal function tests. Serum ceruloplasmin level was normal. MRI brain did not reveal any abnormality. She was started on 1 mg/kg/d of levodopa in three divided doses. Within a few days of therapy, she showed significant improvement. At discharge, she had nearly normal gait. At follow-up of 6 months, she was doing well and had normal neurological examination.

Discussion

Dopa-responsive dystonia represents about 5-10% of primary childhood dystonia(2). Age of onset is usually between 4-8 years but may be as early as infancy. The disorder is more common in females. It is inherited in an autosomal dominant fashion. Occasionally, the condition may occur sporadically(2,3). The causative gene for the disorder has been localized to chromosome 14q and it encodes for enzyme GTP-Cyclohydrolase 1(5).

The clinical presentation is quite characteristic. The dystonia most frequently starts in one or both legs but can involve other parts of the body. The presenting complaint therefore is a gait disturbance including toe-walking, difficulty in walking and frequent falls. The spread of dystonia to other limbs then occurs and follows the pattern of the letter ‘N’. All limbs are affected within 4-5 years(6). Uncommon presentations of DRD include brisk tendon reflexes, extensor plantars (as in our patient), and hypertonia. Cerebellar and sensory disturbances or intellectual deteriora-tion does not occur(3,6). The most character-istic feature of DRD, which virtually clinches the diagnosis of the disorder, is the presence of marked diurnal fluctuations. Dystonia worsens during the day and symptoms are relieved by sleep, but not by rest without sleep(6). This feature may be absent, however in some cases(2). Responsiveness to L-dopa is a key pointer to the diagnosis in such cases(2,3,6).

DRD may be misdiagnosed as cerebral palsy particularly the diplegic variety, because hyperreflexia, extensor plantar responses, and hypertonia with normal intelligence are seen in both. This is more likely to happen when symptoms start during infancy(2,3). Hysteria may be diagnosed because of bizarre nature of initial symptoms (e.g., awkward gait, frequent falls which are not present during the early hours of the day but supervene during the latter part of the day), parent’s inability to describe the symptoms clearly and normal neurological examination(3,6,7). Juvenile Parkinsonism, Wilson’s disease and idiopathic torsion dys- tonia need to be excluded because of thera-peutic as well as prognostic implications(2,3).

Treatment with small doses of L-dopa produces rapid and complete amelioration of symptoms in most patients and this responsiveness stays even if the diagnosis has been made several years after the onset of symptoms(2,8). No other dystonia responds so well to L-dopa. This is an important diagnostic feature of the disorder and is especially helpful when diurnal variations are not marked(6,9). Long-term prognosis is excellent with majority of the patients maintaining continued clinical stability on L-dopa therapy for several years(2). A very small minority of patients, however, develop wearing-off and a less satis-factory response within first few years of treatment. It is likely that these patients represent misclassified cases of childhood onset parkinsonism(2).

In view of the disability associated with dystonia and complete normalization of motor function following treatment, it becomes absolutely necessary that the diagnosis of DRD should always be considered in the differen-tial diagnosis of idiopathic childhood-onset dystonia. A trial with L-dopa may be justified in cases where diagnostic dilemma exists.

Contributors: JSG and RM were involved in literature search and preparation of the manuscript. SB co-drafted and critically evaluated the paper. JSG will act as the guarantor of the paper.

Funding: None
Competing interests: None stated.

 

1. Segawa M, Hosaka A, Miyagawa F, Nomura Y, Imai H. Hereditary progressive dystonia with diurnal fluctuations. In: Advances in Neurology. Eds Eldrige R, Fahn S. New York, Raven Press, 1976; pp 215-253.

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