HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Blumen, S. C. Articles by Braverman, I. PubMed PubMed Citation Articles by Blumen, S. C. Articles by Braverman, I. Related Collections Prognosis Muscle disease Natural history studies (prognosis) All Genetics Trinucleotide repeat diseases

Cognitive impairment and reduced life span of oculopharyngeal muscular dystrophy homozygotes

From the Department of Neurology (S.C.B., R.L.C.) and the Otorhinolaryngology Unit (I.B.), Hillel Yaffe Medical Center, Hadera, Israel; Rappaport Faculty of Medicine (S.C.B., R.L.C., I.B.), Technion, Haifa, Israel; Department of Neurological Sciences (J.-P.B., S.C.), Enfant-Jesus Hospital, Quebec, Canada; CENUM, CRCHUM, University of Montreal (B.B.), Canada; Neurology Service (D.P.), Abarbanel Mental Health Center, Bat Yam, Israel; Department of Neurology (V.E.D.), Tel Aviv Souraski Medical Center, Department of Neurological Rehabilitation (N.B.), Sheba Medical Center, Tel Hashomer, Israel; and Sackler School of Medicine (D.P., V.E.D., N.B.) Tel Aviv University, Israel.

Address correspondence and reprint requests to Dr. Sergiu C. Blumen, Department of Neurology, Hillel Yaffe Medical Center, PO Box 169, Hadera, 38100, Israel navabl{at}hotmail.com

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.

Abbreviations: BED = bedridden; BP = blepharoplasty; CK = creatine kinase; CPM = cricopharyngeal myotomy; ED = esophageal dilation; FC = French-Canadian; GS = feeding gastrostomy; INI = intranuclear inclusion; IRB = institutional review board; OMDP = oculopharyngeal muscular dystrophy; UJ = Uzbek Jewish; WAIS = Wechsler Adult Intelligence Scale; WhC = wheelchair bound.

Disclosure: Author disclosures are provided at the end of the article.

Received November 8, 2008. Accepted in final form May 18, 2009.