Sporadic adult onset dystonia: sensory abnormalities as an endophenotype in unaffected relatives

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Abstract
Background: Most patients with adult onset primary torsion dystonia (AOPTD) have the sporadic form of the disease. They may however be the only manifesting family members of a poorly penetrant genetic disorder. Sensory changes, including structural abnormalities of the primary sensory cortex, are found in AOPTD. Spatial discrimination threshold (SDT), a measure of sensory cortical organisation, is abnormal in AOPTD and in unaffected relatives of patients with familial AOPTD. Our hypothesis was that abnormal SDTs might be found in unaffected relatives of patients with sporadic AOPTD. Methods: SDTs were assessed at the index finger bilaterally by a grating orientation task. Normal age related SDTs were derived from 141 control subjects aged 20–64 years. SDTs were considered abnormal when greater than 2.5 SD above the control mean. In total, 105 of 171 (61%) eligible unaffected siblings and offspring of patients with cervical dystonia had SDT examined. Results: Fourteen of 48 siblings (29%) and 10 of 57 (18%) offspring were found to have an abnormal SDT. Only five of the 20 patients examined had abnormal SDTs. In 11 of the 25 families, no abnormality was found in an unaffected relative. In the 14 families where at least one unaffected relative had an abnormal SDT, 14 of 37 siblings (38%) and 10 of 33 offspring (30%) had abnormal SDTs. Conclusion: Sensory abnormalities found in unaffected relatives of patients with apparently sporadic AOPTD may be a surrogate marker for the carriage of an abnormal gene.