Endophenotyping: a window to the pathophysiology of dystonia.

TLDR: It is shown that even relatively simple clinical testing is able to detect subclinical abnormal spatial discrimination capability (SDT) in unaffected relatives of patients with a genetic condition such as parkinsonism.

Abstract: Neuroimaging-based endophenotyping is becoming popular. The aim is to discover markers for altered CNS gene expression in nonmanifesting gene carriers for illnesses with reduced penetrance, preclinical gene carriers for illnesses with a late onset, and even healthy subjects with allelic variants possibly related to an increased susceptibility for development of given personality traits or psychiatric disorders. As examples, using PET and fMRI, imaging biomarkers have been described for the gene responsible for primary torsion dystonia (DYT1),1 for the Parkin gene mutation responsible for early-onset parkinsonism,2 and for allelic variants in the promoter region of the serotonin transporter implicated in abnormal level of anxiety.3 Neuroimaging endophenotyping is made possible by using highly specialized expensive equipment with well-trained experimenters. These studies cannot determine, however, whether the abnormal activity network associated with the gene is directly gene-related or part of a compensatory mechanism. In this issue of Neurology , O’Dwyer et al.4 show that even relatively simple clinical testing is able to detect subclinical abnormal spatial discrimination capability (SDT) in unaffected relatives of patients with a genetic …