Oculopharyngeal Muscular Dystrophy

InFocus

Oculopharyngeal muscular dystrophy (OPMD) is a form of muscular dystrophy that results from a mutation in the PABPN1 gene.

Although there are no treatments for OPMD — as yet — that address the underlying cellular or molecular abnormalities, there are surgical treatments for the main problems patients experience: droopy eyelids and difficulty swallowing.

This special section (located in the center of Quest for easy removal) includes:

Dear Readers

•;“Fast;Facts”;about;OPMD

•;An;update;on;state-of-the-art;research and;disease;management,;with;first-person;stories;from;people;with;OPMD

•;Information;about;genetic;testing

 

To learn more about OPMD, visit ww.mda.org or call your local MDA office at (800) 572-1717.

OPMD is a form of muscular dystrophy in which symptoms usually first appear between the 30s and 60s, and primarily involve the muscles of the upper eyelids and the swallowing muscles. As these muscles weaken, patients have difficulty keeping their eyes open and find that food and liquids are increasingly hard to swallow. As OPMD progresses, it can weaken the muscles of the limbs, particularly the legs.

The disease is more common in French Canadians, Jews of Central Asian descent (Bukharan Jews), and Hispanics living in New Mexico, than it is in the general population.

The underlying defect is a mutation in a gene on chromosome 14, identified in 1998 by an MDA-supported research team led by Guy Rouleau, who was then at Montreal General Hospital and McGill University in Montreal. (He’s now at the University of Montreal.)

The protein made from this gene is

Fast Facts

called polyadenylate binding protein 1, or PABPN1. Because of the genetic defect in OPMD, the protein is slightly longer than normal, containing extra molecules of the amino acid alanine. The cellular and molecular effects of this lengthening of the PABPN1 protein are the subject of ongoing investigations. One effect is that clumps form in the nucleus of OPMD-affected muscle cells.

OPMD is dominantly inherited, meaning just one mutated PABPN1 gene, passed from one parent to a child, is sufficient to cause disease symptoms.

DNA testing for OPMD has been available for several years. Without DNA testing, it’s usually not possible to detect whether or not a person has inherited the OPMD gene defect until he or she reaches middle age.

MDA’s current commitment to research in oculopharyngeal muscular dystrophy (OPMD), as of July 22, 2009, is $1,635,928, spread over 12 grants.

InFocus:

Stopping a Long Protein From Shortening a Life

By Margaret Wahl

 

Seattle resident Ken Lang (see “Like a Frog,” page 44) says he knew a disease that impairs swallowing and speaking was a possibility for him, because his father, uncle and grandmother had been affected by such a disorder. “I first became symptomatic when I was about 51 or 52,” says Lang, now 62, “although I didn’t get an official diagnosis until about four years ago.” Now a writer and a dispatcher for a transportation company, Lang says his throat muscle problems gradually

increased until he couldn’t even swallow liquids and was having trouble speaking.

Carol Forde (see “Not Glad,” page 38), in Strum, Wis., also has a family history of insidious and specific muscle weakness, although earlier generations didn’t have a diagnosis. “I’m sure it goes back farther than my maternal grandmother, but all we knew was that my grandmother had really, really droopy eyelids, to the point where she would have to sit there with her elbow on the table and use her

Biochemist Anita Corbett (left) and molecular pharmacologist Grace Pavlath are studying OPMD at Emory University in Atlanta.