ABSTRACT
Dyskinesias are involuntary muscle movements that occur spontaneously in Huntington's disease (HD) and after long-term treatments for Parkinson's disease (levodopa-induced dyskinesia; LID) or for schizophrenia (tardive dyskinesia, TD). Previous studies suggested that dyskinesias in these three conditions originate from different neuronal pathways that converge on overstimulation of the motor cortex. We hypothesized that the same variants of the N-methyl-D-aspartate receptor gene that were previously associated with the age of dyskinesia onset in HD were also associated with the vulnerability for TD and not LID. Genotyping patients with LID and TD revealed, however, that these two variants were dose-dependently associated with susceptibility to LID, but not TD. This suggested that LID, TD and HD might arise from the same neuronal pathways, but TD results from a different mechanism.
Subject(s)
Alleles , Dyskinesias/genetics , Genetic Predisposition to Disease/genetics , Genotype , Receptors, N-Methyl-D-Aspartate/genetics , Age of Onset , Antiparkinson Agents/adverse effects , Antipsychotic Agents/adverse effects , Dyskinesia, Drug-Induced/genetics , Dyskinesia, Drug-Induced/physiopathology , Dyskinesias/physiopathology , Gene Expression/genetics , Humans , Huntington Disease/genetics , Huntington Disease/physiopathology , Levodopa/adverse effects , Long-Term Care , Motor Cortex/physiopathology , Movement Disorders/genetics , Movement Disorders/physiopathology , Polymorphism, Single Nucleotide/genetics , Schizophrenia/drug therapyABSTRACT
The aim of the study was to analyze genetic aspects of Chiari type I malformation (CMI) using clinical neurological examination and magnetic resonance imaging data on the craniovertebral region in 13,500 outpatients, 364 inpatients with CMI and 91 first-degree relatives of 47 probands with CMI. Higher CMI frequency (3.9%) in the outpatients with neurological signs, and CMI clinical and morphologic polymorphism have been discovered, the women being mostly affected and the men displaying more severe clinical picture of the disease. In the group of patients with the most severe CMI form, higher parent's endogamy marriage frequency was observed. The CMI clinical and morphologic features in the probands and their relatives were identical and the frequency of the CMI presence in the first-degree relatives depended on the proband's pathology severity. The results obtained support the evidence for CMI multifactorial nature.
