Research progress and diagnostic strategy of genetic pathogenesis of dystonia

Abstract

Dystonia is a syndrome of abnormal involuntary movements that are repetitive, twisting or patterned, and can result in abnormal postures. Genetic factors play an important role in the pathogenesis of dystonia. To date, at least 20 dystonic syndromes have been distinguished on a genetic basis ( DYT1-21 , except DYT14 ), 10 of which have had clear causing genes. Recently, major discoveries have appeared in the genetic field: mutations in the transcription factor THAP1 and DNA replication factor CIP1-interacting zinc finger protein 1 ( CIZ1 ) have been linked to adult-onset primary dystonia; proline-rich transmembrane protein 2 ( PRRT2 ) has been tied to paroxysmal kinesigenic dyskinesia; DYT14 has been redefined as DYT5 due to a deletion mutation in guanosine triphosphate cyclohydrolase 1 ( GCH1 ). In addition, the existing diagnostic algorithms for dystonic syndromes rely on the clinicians' experience, without a streamlined diagnostic pathway. Non-specialist clinicians and neurologists may, therefore, find diagnosis of dystonic syndromes difficult. This review focuses on the molecular and phenotypic features of the hereditary dystonias, with emphasis on recent advances. Also an eight-question approach is proposed in this review to inform specialists and general neurologists on the appropriate diagnostic test for each patient with a possible dystonic syndrome.