Misdiagnoses in children with dopa-responsive dystonia

Dystonia is a state of continuous contraction of groups of agonist and antagonist muscles resulting in a sustained abnormal posture. Dopa-responsive dystonia was first described in 1976 by Segawa. Patients typically have diurnal variation of their symptoms with worsening at the end of the day and a dramatic response to low-dose l-dopa. This report presents five consecutive children with dopa-responsive dystonia who were misdiagnosed initially as spastic diplegic cerebral palsy, intractable epilepsy, hereditary spastic paraplegia, or a neurodegenerative disorder. There were two males and three females aged 3-13 years (mean 8.6 years). They were monitored for up to 2 years (mean 14.8 months). One had focal, one axial, one segmental, and two generalized dystonia. The dystonia was paroxysmal in two (tiptoe walking and opisthotonus), and all had a progressive course. All children responded dramatically to l-dopa (mean 200 mg/day), including three who were wheelchair-bound for several years. The difficulties in early diagnosis, variability of clinical presentation, and dramatic response to l-dopa will be illustrated. To conclude, dopa-responsive dystonia should be considered in any child who presents with paroxysmal or progressive hypertonia of unknown etiology, because it responds so dramatically to l-dopa.

Introduction

Dystonia is defined as a state of continuous contraction of groups of agonist and antagonist muscles resulting in a sustained abnormal posture, which is frequently twisting in nature [1]. Muscle tone typically fluctuates, varying from normal to extreme hypertonia [2]. Oppenheim first described dystonia in 1911; however, the phenomenology, pathophysiology, and management have become much better understood over the last decade [3]. To organize the clinical and etiologic heterogeneity of dystonia, different classifications have been proposed [4]. Clinically, dystonia can be classified according to the age of onset as early (<21 years) or late (>21 years), or according to the distribution of affected body regions as summarized in Table 1 [5]. Dystonic movements usually occur spontaneously. They can be precipitated or worsened by attempts to move and can vary with alterations in emotional state and fatigue. However, dystonia typically diminishes or disappears with distraction or sleep. Dystonia can be subclassified as action induced or posture induced, although secondary dystonia in children is typically present at rest and is increased by action (Table 1). There are many diverse causes of dystonia (Table 2) [6]. It can be primary (idiopathic) or secondary (symptomatic) to neurodegenerative disorders or other lesions of the brain (Table 2). However, with the recent mapping of genes for idiopathic dystonias, the term primary is becoming outdated [7]. Table 3 summarizes an updated genetic classification and highlights recently mapped genes of various inherited dystonias [8].

Dopa-responsive dystonia was first described in 1976 by Segawa [9]. It is a rare inherited primary dystonia plus syndrome (Table 2). Typically, the patient has a diurnal variation with symptoms that are worse by the end of the day [2]. Dopa-responsive dystonia begins at 1-12 years of age (median 6.5), most often with progressive dystonia in a foot and associated alterations in gait [10]. It should be considered in any child who presents with dystonia of unknown etiology because it responds so dramatically to l-dopa. The aim of this article is to provide an updated overview of childhood dystonias with emphasis on dopa-responsive dystonia. Five casesrepresenting my experience with this interesting syndrome are presented. All patients were evaluated and monitored by the author at King Faisal Specialist Hospital and Research Center or King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. All patients were referred for further evaluation of their diagnoses and management, and all had initial misdiagnoses (Table 4). These cases will illustrate the difficulties in early diagnosis, variability of clinical presentation, and dramatic response to l-dopa. The following is a concise summary of the most relevant clinical findings in each of these patients.