|55 Kenosia Avenue
Danbury, CT 06810
Toll Free: 1.800.999.6673
The National Organization for Rare Disorders (NORD) web site, its databases, and the contents thereof are copyrighted by NORD. No part of the NORD web site, databases, or the contents may be copied in any way, including but not limited to the following: electronically downloading, storing in a retrieval system, or redistributing for any commercial purposes without the express written permission of NORD. Permission is hereby granted to print one hard copy of the information on an individual disease for your personal use, provided that such content is in no way modified, and the credit for the source (NORD) and NORD’s copyright notice are included on the printed copy. Any other electronic reproduction or other printed versions is strictly prohibited.
The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.
Copyright 2007, 2012
NORD is very grateful to 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.
Symptoms of the following disorders can be similar to those of OPMD. Comparisons may be useful for a differential diagnosis.
Myasthenia gravis is a neuromuscular disorder primarily characterized by muscle weakness and muscle fatigue. Although the disorder usually becomes apparent during adulthood, symptom onset may occur at any age. The condition may be restricted to certain muscle groups, particularly those of the eyes (ocular myasthenia gravis), or may become more generalized (generalized myasthenia gravis), involving multiple muscle groups. Most individuals with myasthenia gravis develop weakness and drooping of the eyelids (ptosis); weakness of eye muscles, resulting in double vision (diplopia); and excessive muscle fatigue following activity. Additional features commonly include weakness of facial muscles; impaired articulation of speech (dysarthria); difficulties chewing and swallowing (dysphagia); and weakness of the upper arms and legs (proximal limb weakness). In addition, in about 10 percent of cases, affected individuals may develop potentially life-threatening complications due to severe involvement of muscles used during breathing (myasthenic crisis). Myasthenia gravis results from an abnormal immune reaction in which the body's natural immune defenses (i.e., antibodies) inappropriately attack and gradually destroy certain receptors in muscles that receive nerve impulses (antibody-mediated autoimmune response). (For more information on this disorder, choose "myasthenia gravis" as your search term in the Rare Disease Database.)
Chronic progressive external ophthalmoplegia (CPEO or Kearns-Sayre syndrome) is a mitochondrial disorder. Mitochondria are the "energy factories" of cells and contain a separate DNA from the "regular" genes. Inheritance of mitochondrial DNA only occurs through the mother and therefore CPEO passes through the mother's side of the family. Patients with CPEO develop progressive drooping of the eyelids and inability to move the eyes. The poor eye movements are generally symmetric, and patients do not develop double vision. Although mitochondria exist in every cell of the body, many patients do not experience other symptoms. Others may experience a slow or abnormal heart rate, systemic muscle weakness, or visual loss. These patients typically do not suffer from difficulty swallowing or speaking. No specific genetic testing is available to diagnose CPEO, however numerous mutations have been identified for mitochondrial disorders in general. In some instances, a muscle biopsy from the quadriceps in the leg may be performed. It may show a characteristic pattern indicating a mitochondrial disorder. (For more information on this disorder, choose "Kearns-Sayre syndrome" as your search term in the Rare Disease Database.)
Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is a rare disorder that is inherited as an autosomal dominant trait. The main findings of this disorder are eyelids that are abnormally narrow horizontally (blepharophimosis), a vertical fold of skin from the lower eyelid up either side of the nose (epicanthus inversus), and drooping of the upper eyelids (ptosis). There are thought to be two types of the syndrome. Type I BPES may involve female infertility and is inherited as an autosomal dominant genetic trait. Both male and female children of a male with type I BPES have a 50% chance of being affected. If females with type I BPES are able to have children, the odds are 50% that each child (male or female) will have type I BPES. Type II BPES is also transmitted as an autosomal dominant trait meaning that either parent may transmit the disorder and the children have a 50% chance of being affected. Type II is not associated with female infertility. (For more information on this disorder, choose "BPES" as your search term in the Rare Disease Database.)
Oculopharyngodistal myopathy is an extremely rare disorder characterized by droopy eyelids (ptosis) and slowly progressive weakening of muscles of the throat resulting in difficulty swallowing (dysphagia). Affected individuals also experience severe facial muscle weakness, including external eye (ocular) muscles often resulting in limitations in eye movement. Individuals with oculopharyngodistal myopathy also develop weakness of the muscles of the lower legs (distal muscles). Over time, the muscles of the upper legs and arms become involved. Affected individuals may eventually require a wheelchair.
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 (blepharoplasty). 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.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Banwell B. Emery-Dreifuss Muscular Dystrophy. NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:3302.
Bennett JC, Plum F., eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:2161-3.
Ruegg S, Lehky Hagen M, Hohl U, et al. Oculopharyngeal muscular dystrophy - an under-diagnosed disorder? Swiss Med Wkly. 2005;135:574-86.
Brais B. Oculopharyngeal muscular dystrophy: a late-onset polyalanine disease. Cytogenet Genome Res. 2003;100:252-60.
Fan X, Rouleau GA. Progress in understanding the pathogenesis of oculopharyngeal muscular dystrophy. Can J Neurol Sci. 2003;30:8-14.
Becher MW, Morrison L, Davis LE, et al., Oculopharyngeal muscular dystrophy in Hispanic New Mexicans. JAMA. 2001;286:2437-40.
Hill Me, Creed GA, McMullan TF, et al., Oculopharyngeal muscular dystrophy: phenotypic and genotypic studies in a UK population. Brain. 2001;124:522-6.
Blumen SC, Korczyn AD, Lavoie H, et al., Oculopharyngeal MD among Bukhara Jews is due to a founder (GCG)9 mutation in the PABP2 gene. Neurology. 2000;55:1267-70.
Brais B, Rouleau GA, Bouchard JP, Fardeau M, Tome FM. Oculopharyngeal muscular dystrophy. Semin Neurol. 1999;19:59-66.
Brais B, Phil M, Rouleau GA. (Updated June 22, 2006). Oculopharyngeal Muscular Dystrophy. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2012. Available at http://www.genetests.org. Accessed November 5, 2012.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Oculopharyngeal Muscular Dystrophy; OPMD. Entry No: 164300. Last Edited July 27, 2012. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed November 5, 2012.
Urtizberea JA. Oculopharyngeal muscular dystrophy. Orphanet encyclopedia. http://www.orpha.net/data/patho/GB/uk-OPMD.pdf. Updated February 2004. Accessed November 5, 2012.
Report last updated: 2012/11/06 00:00:00 GMT+0