title: Cognitive impairment and reduced life span of oculopharyngeal muscular dystrophy homozygotes.
abstract: OBJECTIVE
  To assess the evolution and life expectancy in patients with oculopharyngeal muscular dystrophy (OPMD) who are homozygotes for two (GCN)13 expansions in the PABPN1 encoding gene.
  
  
  BACKGROUND
  OPMD is particularly frequent among French Canadians (FCs) and Uzbek Jews (UJs), who carry a same size, (GCN)13, PABPN1 mutation. The high rate of consanguinity among UJs together with late disease onset and normal fertility results in homozygous cases.
  
  
  METHODS
  For 15 to 20 years, we followed 4 FC and 6 UJ homozygotes with OPMD and compared them with their heterozygous parents and siblings. In addition to clinical evaluation, electrodiagnostic tests, psychological tests, and brain imaging studies were performed.
  
  
  RESULTS
  In all (GCN)13-(GCN)13 patients, OPMD started before age 35 years, with bilateral ptosis and dysphagia; external ophthalmoparesis and dysphonia followed within a few years, as well as weakness in proximal limb muscles. All patients had recurrent aspirations and lost weight; 4 patients required surgical interventions to alleviate dysphagia, and 5 required feeding gastrostomies. Most patients were followed by psychiatrists due to cognitive decline, recurrent depression, or psychotic episodes. Six patients died at ages 50, 51, 53, 56, 56, and 57 years. The eldest patient is now 51 years old; she is cachectic and requires special diet and psychiatric care for paranoid psychosis and uninhibited behavior.
  
  
  CONCLUSIONS
  Oculopharyngeal muscular dystrophy progresses faster in homozygote compared with heterozygote patients. It is not restricted to the muscles, but also involves the CNS with cognitive decline and psychotic manifestations and leads to a reduced life expectancy.
authors.affiliation: Department of Neurology, Hillel Yaffe Medical Center, PO Box 169, Hadera, 38100, Israel. navabl@hotmail.com
authors.forename: S C
authors.initials: SC
authors.lastname: Blumen
authors.forename: J-P
authors.initials: JP
authors.lastname: Bouchard
authors.forename: B
authors.initials: B
authors.lastname: Brais
authors.forename: R L
authors.initials: RL
authors.lastname: Carasso
authors.forename: D
authors.initials: D
authors.lastname: Paleacu
authors.forename: V E
authors.initials: VE
authors.lastname: Drory
authors.forename: S
authors.initials: S
authors.lastname: Chantal
authors.forename: N
authors.initials: N
authors.lastname: Blumen
authors.forename: I
authors.initials: I
authors.lastname: Braverman
mesh_terms: D003072:Cognition Disorders / Q000150:complications / Q000235:genetics / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008017:Life Expectancy; D008136:Longevity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D039141:Muscular Dystrophy, Oculopharyngeal / Q000150:complications / Q000235:genetics / Q000401:mortality*