Oculopharyngeal muscular dystrophy is a genetic condition characterized by muscle weakness that begins in adulthood, typically after age 40. The term "oculopharyngeal" refers to the eyes (oculo-) and a part of the throat called the pharynx (-pharyngeal). Affected individuals usually first experience weakness of the muscles in both eyelids that causes droopy eyelids (ptosis). Ptosis can worsen over time, causing the eyelid to impair vision, and in some cases, limit eye movement. Along with ptosis, affected individuals develop weakness of the throat muscles that causes difficulty swallowing (dysphagia). Dysphagia begins with dry food, but over time, liquids can also become difficult to swallow. Dysphagia can cause saliva to accumulate and a wet-sounding voice. Many people with oculopharyngeal muscular dystrophy also have weakness and wasting (atrophy) of the tongue. These problems with food intake may cause malnutrition, choking, or a bacterial lung infection called aspiration pneumonia.

Mutations in the PABPN1 gene cause oculopharyngeal muscular dystrophy. The PABPN1 gene provides instructions for making a protein that is found throughout the body. The PABPN1 protein plays an important role in processing molecules called messenger RNAs (mRNAs), which serve as genetic blueprints for making proteins. PABPN1 alters a region at the end of mRNA molecules that protects mRNA from being broken down. The PABPN1 protein also is involved in transporting mRNA within the cell.

In Europe, the prevalence of oculopharyngeal muscular dystrophy is estimated to be 1 in 100,000 people. This condition is much more common in the French-Canadian population of the Canadian province of Quebec, where it is estimated to affect 1 in 1,000 individuals. Oculopharyngeal muscular dystrophy is also seen more frequently in the Bukaran Jewish population of Israel, affecting 1 in 700 people.

Most cases of oculopharyngeal muscular dystrophy are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, some individuals have mutations in both copies of the PABPN1 gene that lead to expanded polyalanine tracts. These individuals tend to have more severe signs and symptoms that develop earlier in life compared to individuals with a mutation in one copy of the gene.

Published Date: February 01, 2018
Published By: National Institutes of Health