Expansion of the clinicopathological and mutational spectrum of Perry syndrome

Parkinsonism Relat Disord. 2014 Apr;20(4):388-93. doi: 10.1016/j.parkreldis.2014.01.010. Epub 2014 Jan 22.

Abstract

Background: Perry syndrome (PS) caused by DCTN1 gene mutation is clinically characterized by autosomal dominant parkinsonism, depression, severe weight loss, and hypoventilation. Previous pathological studies have reported relative sparing of the cerebral cortex in this syndrome. Here, we characterize novel clinical and neuroimaging features in 3 patients with PS.

Methods: (18)F-fluorinated N-3-fluoropropyl-2-ß-carboxymethoxy-3-β-(4-iodophenyl) nortropane ([(18)F]FP-CIT) PET, [(18)F]fluorodeoxyglucose PET, or volumetric MRI was performed in probands, and imaging data were analyzed and compared with those of control subjects.

Results: We identified 2 novel mutations of DCTN1. Oculogyric crisis that presented before levodopa treatment was observed in 1 case. One patient had supranuclear gaze palsy. In 2 cases, [(18)F]FP-CIT showed marked loss of dopamine transporter binding with only mild parkinsonism. Areas of hypometabolism or cortical thickness change were observed in dorsolateral frontal, anterior cingulate, lateral temporal, and inferior parietal cortices.

Conclusion: Oculomotor manifestations are not uncommon in PS. Neuroimaging studies suggest involvement of the frontotemporoparietal cortex, which may be the clinical correlate of apathy and depression, as well as pathological changes in subcortical structures.

Keywords: DCTN1; MR volumetry; Novel mutation; Perry syndrome; Positron-emission tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Depression / genetics
  • Depression / pathology
  • Dynactin Complex
  • Female
  • Humans
  • Hypoventilation / genetics*
  • Hypoventilation / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Microtubule-Associated Proteins / genetics*
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Parkinsonian Disorders / genetics*
  • Parkinsonian Disorders / pathology*
  • Positron-Emission Tomography
  • Radiopharmaceuticals

Substances

  • DCTN1 protein, human
  • Dynactin Complex
  • Microtubule-Associated Proteins
  • Radiopharmaceuticals

Supplementary concepts

  • Perry Syndrome