Paroxysmal dystonic choreoathetosis linked to chromosome 2q: clinical analysis and proposed pathophysiology

We describe clinical features of a large Polish-American kindred in which autosomal-dominant, paroxysmal dystonic choreoathetosis (PDC) was linked to a locus on chromosome 2q. Episodes of generalized dystonia and choreoathetosis involving the face and all extremities began in early childhood, lasted for 30 minutes to several hours, and occurred up to several times each week. There was no interruption of consciousness and EEGs were normal during the episodes. Paroxysmal dyskinesia occurred at rest both spontaneously and following caffeine or alcohol consumption. Neurologic examinations were normal between attacks. The cause of PDC is unknown. We deduced a model of PDC pathophysiology from analyzing neurophysiologic effects of alcohol and caffeine (which provoke attacks of PDC), the variably beneficial effects of levodopa-carbidopa, and the occurrence of dystonia and paroxysmal dyskinesia in biopterin synthesis disorders. We propose that nigrostriatal neurons in PDC patients have either marginally deficient dopamine synthesis or excessive alcohol- and caffeine-induced dopamine release; and that following alcohol- and caffeine-induced dopamine release, PDC patients experience a period of dopamine deficiency.