NORD gratefully acknowledges Dr. Michael Lee, Professor of Ophthalmology, Neurology, and Neurosurgery, University of Minnesota, for their assistance in creating this report.
Oculopharyngeal muscular dystrophy (OPMD) is a rare genetic muscle disorder with onset during adulthood most often between 40 and 60 years of age. OPMD is characterized by slowly progressive muscle disease (myopathy) affecting the muscles of the upper eyelids and the throat. Affected individuals may develop drooping of the eyelids (ptosis), trouble moving their eyes (ophthalmoplegia) and/or difficulty swallowing (dysphagia). Double vision (diplopia) is uncommon. Eventually, additional muscles may become involved including those of the upper legs and arms (proximal limb weakness). In some cases, muscle weakness of the legs may eventually cause difficulty walking. OPMD may be inherited as an autosomal dominant or recessive trait.
OPMD belongs to a group of rare genetic muscle disorders known as the muscular dystrophies. These disorders are characterized by weakness and atrophy of various voluntary muscles of the body. Approximately 30 different disorders make up the muscular dystrophies. The disorders affect different muscles and have different ages of onset, severity and inheritance patterns. Unlike OPMD, most forms of muscular dystrophy have onset during childhood or adolescence.
Although the defective gene that causes OPMD is present at birth, the symptoms usually do not appear until adulthood sometime between 40 and 60 years of age. OPMD is characterized by progressive weakness of certain muscles around the eyes, in the throat, and less commonly in the pelvic and shoulder areas including the muscles of the upper legs and arms.
The rate of progression and specific symptoms associated with OPMD vary greatly from case to case even among members of the same family. The two most common initial symptoms of OPMD are drooping of the upper eyelid (ptosis) and difficulty swallowing. Ptosis can cause visual impairment if the eyelids droop over the pupils obstructing sight. As a result, some affected individuals may tilt their head back to compensate. Both eyes are usually affected (bilateral). Eventually, additional muscles around the eye may gradually weaken; potentially restricting the movements of the eyes, but this is rarely complete. Some individuals with OPMD may develop double vision (diplopia).
Affected individuals who experience difficulty swallowing may feel as if food is getting stuck in their throats. If swallowing difficulties become severe enough, they can lead to the ingestion of food or liquids into the lungs (aspiration), which can cause inflammation or infection of the lungs (aspiration pneumonia).
As the disease progresses, some individuals will develop weakness and degeneration (atrophy) of the muscles of the upper legs (proximal muscles). Proximal muscles are the muscles that are closest to the center of the body such as the muscles of the shoulder, pelvis, and upper arms and legs. Muscle weakness may spread from the proximal muscles to affect distal muscles. Distal muscles are those farther from the center of the body and include the muscles of the lower arms and legs and the hands and feet. The distal muscles of the legs may become involved in some cases of OPMD.
Weakness of the muscles of legs does not correlate to the severity of muscle weakness of the eyelids or throat and can occur early in the disease or later. It may be mild or severe. In severe cases, weakness of the leg muscles can affect an individual’s ability to kneel, climb stairs, squat, or walk. In approximately 10 percent of cases, affected individuals may eventually require a wheelchair.
Additional symptoms may eventually occur including weakness and degeneration (atrophy) of the tongue, weakness and atrophy of the proximal muscles of the arms, limitation of upward gaze, difficulty speaking (dysphonia), and weakness of additional facial muscles.
OPMD may be inherited as an autosomal dominant or recessive trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
Investigators have determined that OPMD is caused by disruptions or changes (mutations) of the polyadenylate binding protein nuclear 1 (PABPN1) gene located on the long arm (q) of chromosome 14 (14q11.2-q13. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
OPMD is a rare disorder that affects males and females in equal numbers. The disorder has been reported in approximately 29 countries. The largest grouping (cluster) of cases was reported in French descendents in Quebec, Canada (1 in 1000). Clusters have also been reported in the Bukhara Jews of Israel and a Hispanic population of New Mexico. One published report estimated the prevalence of OPMD in France at 1 in 100,000 individuals.
The autosomal dominant form of OPMD is more common than the autosomal recessive form. OPMD was first reported in the medical literature in 1915. The muscular dystrophies affect approximately 250,000 people in the United States.
A diagnosis of OPMD is suspected based upon a thorough clinical evaluation, a detailed patient history, and identification of characteristic findings. A diagnosis is confirmed through commercially available blood tests that can detect the specific genetic abnormality associated with OPMD (i.e., mutation of the PABPN1 gene).
The treatment of OPMD is directed toward the specific symptoms that are apparent in each individual. Ptosis may be treated cautiously with plastic surgery on the eyelids (blepharoptosis repair). The goal of surgery is to raise the eyelids above the visual axis so the patient may see. However, because the muscles that close the eyelids are weak, the patient may not be able to completely close their eyelids after surgery. In cases where difficulty swallowing (dysphagia) is severe, a surgical procedure known as cricopharyngeal myotomy may be used. 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. In other cases, a feeding tube can be placed directly into the small intestine to bypass swallowing altogether.
Orthopedic devices such as canes, leg braces, or walkers can assist individuals who have difficulty walking. Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
Various medications and procedures have been studied for the treatment of individuals with OPMD. Injection of botulinum toxin into the cricopharyngeal muscle has been used to treat individuals with dysphagia. In France, researchers have been studying the use of myoblast injection into the cricopharyngeal muscle to treat dysphagia. More research is necessary to determine the long-term safety and effectiveness of such potential treatments for individuals with OPMD.
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