Oculopharyngeal muscular dystrophy

Oculopharyngeal muscular dystrophy (OPMD) is a genetic disorder characterized by slowly progressing muscle disease (myopathy) affecting the muscles of the upper eyelids and the throat. Onset is typically during adulthood, most often between 40 and 60 years of age. Symptoms may include: eyelid drooping (ptosis), arm and leg weakness, and difficulty swallowing (dysphagia).^[1] There are two types of OPMD, distinguished by their patterns of inheritance. They are known as the autosomal dominant and autosomal recessive types.^[2] Both types are caused by mutations in the PABPN1 gene.^[1][2]Treatment depends on the signs and symptoms present in each individual. Ptosis and dysphagia can be managed with surgery; however, recurrence of symptoms commonly occurs 5-15 years after intervention.^[1][3]

OPMD is characterized by muscle weakness that begins in adulthood, typically after age 40. The first symptom in people with this disorder is usually droopy eyelids (ptosis), followed by difficulty swallowing (dysphagia). The swallowing difficulties begin with food, but as the condition progresses, liquids can be difficult to swallow as well. Many people with this condition have weakness and wasting (atrophy) of the tongue. These problems with food intake may cause malnutrition. Some affected individuals also have weakness in other facial muscles.^[1][2][3][4]

Individuals with OPMD may also have double vision (diplopia) and frequently have weakness in the muscles near the center of the body (proximal muscles), particularly muscles in the upper legs and hips. The weakness progresses slowly over time, and people may need the aid of a cane or a walker. Rarely, affected individuals need wheelchair assistance.^[1][2][3][4]

It is not possible to predict exactly how oculopharyngeal muscular dystrophy will impact one's life. Although the common signs and symptoms have been well studied, the age in which symptoms appear and the severity varies.^[4]

Typically the life expectancy of people with this condition is not reduced.^[4]  Some people with oculopharyngeal muscular dystrophy may need a cane or a walker as the disease worsens over time.[964]  Rarely, an individual may need a wheelchair due to severe lower body muscle weakness.^[5]

OPMD is caused by mutations in the PABPN1 gene. The PABPN1 gene provides instructions for making the PABPN1 protein that is active (expressed) throughout the body. In cells, the PABPN1 protein plays an important role in processing molecules called messenger RNAs (mRNAs), which serve as genetic blueprints for making proteins. The protein acts to protect the mRNA from being broken down and allows it to move within the cell.^[2][4]

The PABPN1 gene contains a section of DNA called a GCN repeat, which normally repeats around 10 times. In cases of OPMD, this section of DNA is repeated 11-17 times. This results in the protein having too many of an amino acid called alanine. The extra alanine causes the PABPN1 protein to form clumps within muscle cells that cannot be broken down. These clumps are thought to impair the normal function of muscle cells and eventually cause cells to die. The progressive loss of muscle cells most likely causes the muscle weakness seen in people with OPMD. It is not known why abnormal PABPN1 proteins seem to affect muscle cells in only certain parts of the body.^[2][4]

Most cases of OPMD are inherited in an autosomal dominant manner, which means one copy of the altered (mutated) gene in each cell is sufficient to cause the condition.^[2][4] Individuals have two copies of each gene; one copy having been inherited from each parent. An individual with the autosomal dominant form of OPMD may have inherited the condition from an affected parent, or less commonly, the condition may occur for the first time in the affected individual. Each child of an affected individual with this form of OPMD has a 50% (1 in 2) chance to be affected and a 50% chance to be unaffected.

Less commonly, OPMD is inherited in an autosomal recessive manner, which means that both copies of the disease-causing gene in each cell must have a mutation for an individual to be affected. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene (and are referred to as carriers), but they typically do not show signs and symptoms of the condition.^[2] When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) chance to be affected, a 50% (1 in 2) chance to be a carrier like each of the parents, and a 25% chance to be unaffected and not be a carrier. The children of an individual with autosomal recessive OPMD will always be carriers (obligate heterozygotes) for the disease-causing mutation. The risk of a child being affected if his/her parent has autosomal recessive OPMD is less than 1%.^[4]

The autosomal dominant form of oculopharyngeal muscular dystrophy (OPMD) is most common among a population of Bukharan Jews living in Israel, where an estimated 1 person in 600 is affected. OPMD is additionally estimated to occur in 1 in 1000 individuals of French-Canadian ancestry and 1 in 100,000 individuals in France. In the United States, the number of people with OPMD is not known, however the majority of diagnosed individuals are of French-Canadian, Ashkenazi Jewish, or Spanish American background.^[4]

The autosomal recessive form of OPMD is estimated to occur in 1 in 10,000 individuals in France, Quebec, and Japan. This estimate is based the number of individuals found to be carriers in these populations (carrier frequency).^[4]

Treatment of oculopharyngeal muscular dystrophy (OPMD) mainly focuses on the specific signs and symptoms present in each individual. Severe drooping of the eyelid (ptosis) may be treated with plastic surgery on the eyelid (blepharoplasty). The goal of this surgery is to raise the eyelid so that the affected individual can see. Individuals with severe difficulty swallowing (dysphagia) may have a surgical procedure known as cricopharyngeal myotomy. In this procedure, the cricopharyngeal muscle of the throat is cut so that when swallowing occurs, the muscle remains relaxed allowing the passage of food or liquid. Orthopedic devices such as canes, leg braces, or walkers can assist individuals who have difficulty walking. Other treatment is symptomatic and supportive.^[1][4]

The National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. If you are interested, click on the above and type "oculopharyngeal muscular dystrophy" into the search box.

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Bethesda, Maryland 20892-2655
Toll-free: 800-411-1222
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Email: prpl@mail.cc.nih.gov
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To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.