Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by progressive ptosis (drooping eyelids) and dysphagia (swallowing difficulties). In addition, affected individuals may develop dysphonia (vocal impairment), impairment of ocular movements, and weakness of the proximal limb muscles, facial muscles, and/or tongue. The onset of OPMD is typically after age 40 and the course is slowly progressive. The penetrance of OPMD is agedependent but is essentially complete by age 70. In general, lifespan is not affected in OPMD patients, although the presence of significant dysphagia leads to an increased risk of malnutrition, choking, and aspiration pneumonia. The vast majority of OPMD cases are inherited in an autosomal dominant manner, but a few families have been found to segregate an autosomal recessive form. OPMD is caused by expansion of a polyalanine repeat in the first exon of PABPN1 (formerly known as PABP2), a gene located on chromosome 14 at band q11.2 that encodes a nuclear polyadenylatebinding
protein. PABPN1 is ubiquitously expressed and functions in the formation of messenger RNA poly-A tails. The expansion that causes OPMD was initially described as an increase in the number of GCG repeats from 6 in a normal allele (GCG6) to between 8 and 13 in pathogenic alleles (GCG8 to GCG13). However, it is now known that the repeat expansion involves a longer stretch of alanine codons that may include both GCG and GCA trinucleotides (both encode the amino acid alanine). Therefore, the normal PABPN1 allele contains 10 alanine codons (GCN10), while pathogenic alleles that cause the autosomal dominant form of OPMD contain between 12 and 17 (GCN12 to GCN17). Those with the autosomal recessive form of OPMD carry two copies of the GCN11 allele, an allele with an estimated prevalence between 1% and 2% in North America, Europe, and Japan. The overall prevalence of OPMD is estimated to be approximately 1 in 100,000 in France, but the condition is highly prevalent among French Canadians and Bukhara Jews, with
an incidence as high as 1 in 600. The prevalence of OPMD in the United States has not been reported.