Oculopharyngeal muscular dystrophy (OPMD) is an inherited disease of the muscles (myopathy) that progresses slowly, mainly affecting muscles of the upper eyelids and the throat. Treatment depends on the signs and symptoms present in each person.
The symptoms of OPMD usually appear between ages of 40 to 60. They may include drooping eyelids (ptosis), difficulties in swallowing (dysphagia), and weakness in the arms and legs.
OPMD is caused by mutations in the PABPN1 gene, which contains the instructions for making the polyadenylate binding protein (PABPN1). The gene is located on chromosome 14, which is present in two copies in every cell of the body, one inherited from the mother and one inherited from the father.
The normal PABN1 protein plays an important role in processing molecules called messenger RNAs (mRNAs), which are copies of a gene that can be read by a cell’s protein-making machinery. The PABN1 protein protects the mRNA from being broken down, allowing it to move within the cell.
At least 10 different mutations in PABPN1 have been identified that can cause OPMD. All result in a PABPN1 protein with a longer stretch of the same amino acid — the building blocks of proteins — that is called alanine. In a normal PABN1 protein, alanine is repeated 10 times in a row, in what is called a poly-alanine tract. In OPMD patients, 11 to 17 alanines are aligned a row in the PABN1 protein. These extra alanines cause the PABPN1 protein to form clumps within muscle cells, and these clumps are thought to hamper the cells’ ability to work as intended and, eventually, to kill them.
The loss of muscle cells over time is the most likely cause of the muscle weakness experienced by people with OPMD. The actual function of the polyalanine tract in a normal PABN1 protein is not fully understood.
The autosomal dominant form of OPMD is caused by a mutation in only one of the gene on chromosome 14, inherited from one parent only. Children of a man or woman with the autosomal dominant form of the disease have a 50-50 chance of inheriting the mutated gene and developing OPMD.
In autosomal dominant forms, the PABPN1 protein usually has between 12 and 17 alanines in a row.
The recessive form of OPMD results from mutations in both copies of the gene, one abnormal gene inherited from each parent. Parent of a child with autosomal recessive OPMD each carry one copy of the mutated gene but typically do not show any disease signs or symptoms.
In autosomal recessive forms, the PABPN1 protein usually has 11 alanines in a row.
Genetic testing is the principal means of diagnosing OPMD. Tests in childhood that could predict the disease are not recommended because of its late onset and relatively mild course.
Most laboratories do not give direct access to these tests to patients or their families. It is best to ask a healthcare provider or genetics professional to request such a genetic test.
The disease is most often found in French-Canadian families or those of French-Canadian descent, as well as among Hispanics of northern New Mexico and Ashkenazi Jews. This disease, however, can affect people of any ethnic or racial origin.
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