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 one of nine types of muscular dystrophy, primarily affecting voluntary muscles. 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). As the disease slowly progresses, the muscle weakness can extend into the neck and shoulders. In time, OPMD may affect the arms and legs and lead to trouble with walking. OPMD generally does not shorten a person’s lifespan.
Common symptoms of OPMD include:
- Eyelid drooping. This may be severe enough to need special glasses (to brace the eyelids open) or surgery (to raise the eyelids).
- Choking or swallowing problems (dysphagia). Dry foods may be the first to cause trouble, but swallowing liquids can later be a challenge.
- Tongue shrinking
- Pooling of saliva
- Facial muscle weakness
- Leg and arm weakness
About 5% to 10% of people with OPMD may develop more severe upper leg weakness that may eventually require wheelchair use.
OPMD is usually inherited in a dominant pattern, meaning only one copy of the gene responsible for the defect is needed to cause the disease. In rare cases, OPMD may show a recessive pattern of inheritance, meaning the person with OPMD got two copies of the defective gene, one from each parent.
OPMD is caused by an expansion mutation in the gene encoding for polyadenylated RNA-binding protein1 (PABPN1). The PABPN1 gene provides instructions for making a 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 alters a region at the end of the mRNA molecule that protects the mRNA from being broken down and allows it to move within the cell. In OPMD, aggregation of expanded PABPN1 form clumps within muscle cells that accumulate because they cannot be broken down. These clumps (called intranuclear inclusions) are thought to impair the normal functioning of muscle cells and eventually cause cell death.
OPMD is a rare disorder that affects males and females in equal numbers. The disorder has been reported in approximately 29 countries. The largest cluster of cases was reported in French descendants 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.
The diagnosis of OPMD is based on the clinical criteria of Brais and colleagues (1993) and is genetically confirmed by detection of a mutation in the PABPN1 gene. The major diagnostic criteria of Brais are 1) positive family history, 2) ptosis or previous surgical correction, and 3) dysphagia. Minor criteria are onset after 40 years; limitation of eye movements; and facial, tongue, and limb weakness. Exclusion criteria are severe external ophthalmoplegia before the age of 60, and the presence of myotonia. A thorough physical exam will be performed and tests may also include times swallowing tests, electromyography, blood tests and muscle biopsy to look for OPMD PABPN1 clumps – which is not required if the genetic tests are positive.
There is no cure for OPMD, but there are various treatments that help manage the symptoms. For patients where ptosis interferes with vision, surgery can be performed to lift droopy eyelids. Speech pathologists can monitor and assess the progression of dysphagia. Assessments of the ability to swallow can help identify people who are at risk for aspiration pneumonia — lung infection due to the ‘breathing in’ of food or liquids. Aspiration pneumonia and its complications can be prevented with careful monitoring. Surgery may also help relieve problems due to dysphagia and should be considered if there is marked weight loss, near-fatal choking, or recurrent pneumonia. Upper arm and shoulder weakness that limits function can be addressed with adaptive techniques through occupational therapy.
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