Executive functions are impaired in heterozygote patients with oculopharyngeal muscular dystrophy

Raffaele Dubbioso, Pasquale Moretta, Fiore Manganelli, Chiara Fiorillo, Rosa Iodice, Luigi Trojano, Lucio Santoro

Research output: Contribution to journalArticle

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disorder caused by a small expansion of a short polyalanine tract in poly(A) binding protein nuclear 1 (PABPN1). It presents with adult onset of progressive eyelid drooping, swallowing difficulties and proximal limb weakness, usually without involvement of central nervous system (CNS). However, cognitive decline with relevant behavioural and psychological symptoms has been recently described in homozygous patients. In this study, we performed for the first time an extensive neuropsychological and neuropsychiatric evaluation on 11 OPMD heterozygote patients. We found that they were less efficient than a matched control sample on several tests, particularly those tapping executive functions. Moreover, the presence of negative correlation between GCN expansion size and some neuropsychological scores raises the issue that CNS involvement might be linked to the genetic defect, being worse in patients with larger expansion. Our results might be consistent with the toxic gain-of-function theory in the pathogenesis of OPMD and hint at a possible direct role of PABPN1 in the CNS also in heterozygote patients.

Original languageEnglish
Pages (from-to)833-837
Number of pages5
JournalJournal of Neurology
Volume259
Issue number5
DOIs
Publication statusPublished - May 2012

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Keywords

  • Central nervous system
  • Executive defects
  • GCN expansion
  • Heterozygote patients
  • Oculopharyngeal muscular dystrophy
  • Psychiatric disturbances

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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