Rapid-Onset Dystonia-Parkinsonism: A Family Affair
Abstract & Commentary
Source: Pittock SJ, et al. Rapid-onset dystonia-parkinsonism: A clinical and genetic analysis of a new kindred. Neurology 2000;55:991-995.
The differential diagnosis of dystonia in- cludes four major categories: primary dystonia (genetic disorders such as DYT-1 dystonia characterized by dystonia in isolation), secondary dystonia (following insults to the brain), heredo-degenerative dystonia (seen in disorders such as X-linked dystonia/parkinsonism, Wilson’s disease, and glutaric aciduria), and dystonia-plus syndromes. The last group includes several rare conditions, including dopa-responsive dystonia, tyrosine hydroxylase deficiency, biopterin deficiency diseases, myoclonus-dystonia, and rapid-onset dystonia-parkinsonism (RDP). These disorders are rare, and the complexity of their clinical phenotypes and genetics make them among the most interesting conditions in movement disorders.
In this paper, Pittock and colleagues report only the third published family with RDP. This condition is an autosomal dominant movement disorder with incomplete penetrance, and has been previously linked in two other families to chromosome 19. Diagnostic criteria for the condition include the sudden development (over hours to days) of dystonia and parkinsonism, preferentially involving the bulbar and arm musculature. Neuroimaging studies are normal in these patients, and the condition is typically poorly responsive to treatment with levodopa or dopamine agonists.
Eight affected individuals were identified in this three-generation kindred. Four had classic symptoms of dystonia-parkinsonism described above, and three developed symptoms after an identified stress or trauma. Four others had unusual features, including stable hemidystonia without bulbar involvement, preferential leg involvement, and intermittent dystonia. In most patients, symptoms stabilized one to two months after onset, and many were significantly disabled by their condition.
A new finding in this kindred was the high incidence of psychiatric symptoms. Three patients had significant social difficulties before the onset of their movement disorder, and three had symptomatic depression. Prior reports had suggested that HVA levels were low in patients with RDP, although this was not a constant finding in the current kindred. An autopsy of the father of the proband revealed no neuronal loss and no Lewy bodies.
Commentary
This paper is of considerable interest to movement disorder clinicians. RDP is so rare that few patients are likely to be diagnosed with the disorder. However, several features of this illness are intriguing. It is one of the few neurologic conditions where an individual who is previously well can develop severe dystonia and/or parkinsonism in a matter of hours, without an obvious insult such as exposure to a toxin or infectious agent. Further, the pathology is unrevealing, and the lack of response to dopaminergic agents suggest that this disorder is neurochemically distinct from its cousin, dopa-responsive dystonia. Ultimately, identification of the gene responsible for RDP will likely answer many questions about this unusual and devastating condition. —Steven Frucht
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