| Disease Name | autosomal dominant (AD) | | NMD Category | Muscular Dystrophy | | Clinical Onset | 4th to 8th decade. | | Clinical Findings | Oculopharyngeal muscular dystrophy (OPMD) occurs predominantly among French-Canadians who are descended from French immigrants, a man and wife who emigrated to Canada in 1634. It has been identified only occasionally in other populations (Emery AEH: Neuromus Disorders 12:343-9, 2002).
OPMD can be inherited as an autosomal dominant or recessive trait. It is characterized by late-onset (usually after the age of 45 years) eyelid drooping (ptosis) and swallowing difficulty (dysphagia). The signs for the autosomal recessive form are the same as for autosomal dominant, but symptoms appear later, typically after 60 years of age, and are generally milder.
Other signs that may be associated with OPMD with disease progression are (in order of prevalence): tongue atrophy and weakness, proximal lower extremity weakness, dysphonia, limitation of upward gaze, facial muscle weakness, and proximal upper extremity weakness.
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| | Diagnostic Work-up | Family history can help identify type of OPMD inheritance. Autosomal dominant OPMD will have a positive family history with involvement of two or more generations. Family history for autosomal recessive OPMD will be consistent with autosomal recessive inheritance (ie, affected sibs without affected parents and/or parental consanguinity). The diagnosis of both dominant and recessive OPMD is established by the identification of a short GCG triplet repeat expansion in the PABPN1 gene (chromosomal locus 14q11.1).
Previously the diagnosis of OPMD was based on the presence of intranuclear inclusions (INI) on muscle biopsy; now muscle biopsy is only warranted in those patients with normal results on genetic testing. Electromyography (EMG) of weak muscles usually reveals discrete signs of a myopathic process, and in most cases serum CK concentration is normal or only slightly elevated (2-5x) in patients with severe leg weakness. Prenatal testing is available, but requests are uncommon because of the late onset and relatively mild physical limitations caused by this disease.
Differential Diagnosis: Myotonic muscular dystrophy, autosomal dominant distal myopathy, mitochondrial myopathy, myasthenia gravis, polymyositis, and progressive bulbar palsy are all differential diagnosis. See GeneClinics review of OPMD for detailed list of differentials.
GeneClinics http://www.geneclinics.org provides a state-of-the-science review of oculopharyngeal muscular dystrophy and a list of diagnostic labs that offer genetic testing.
| | Treatment Notes | No medical treatment is presently available for OPMD. Surgical treatments are used to correct the ptosis and improve swallowing in moderately to severely affected individuals. Surgery is recommended when the ptosis interferes with vision or appears to cause cervical pain secondary to the constant dorsiflexion of the neck. Surgical intervention for symptomatic dysphagia should be considered in the presence of marked weight loss, near-fatal choking (which is extremely rare), or recurrent pneumonia
Progression: Autosomal dominant severe forms (about 5-10% of cases) show earlier onset of ptosis and dysphagia (age less than 45 years). These patients develop incapacitating proximal leg weakness that starts before age 60 years. Some of these patients eventually need a wheelchair. Life expectancy is not reduced. Generally, OPMD is slowly progressive, with ptosis (mean age at onset is 48 years; range 26-65 years) and swallowing problems (mean age at onset 50.7 years; range 40-63 years) common as disease progresses. Most patients develop some degree of muscle weakness in the shoulder and pelvic girdles. OPMD does not appear to reduce life span, but quality of life in later years can be greatly diminished. Early symptoms that can signal onset of swallowing problems are an increased time needed to complete a meal and an acquired avoidance of dry foods.
| | Protein ID | 10 | | Gene Location | 14q11.1.2-q13 | | Abstract | Disease inheritance is both autosomal dominant and autosomal recessive. Autosomal recessive inheritance requires that both the mother and father have at least one copy of an altered gene located on one of the 22 autosomes (that is, not the X or Y chromosomes). These parents may be carriers who show no signs of the disease (i.e., each has one copy of an altered gene), but they have a 25% chance of producing either a normal child or a child with the disease; they have a 50% chance of producing offspring who are carriers with no signs of disease. Two affected parents (i.e., each has two copies of an altered gene) usually produce children who are all affected. Males and females are at equal risk for being affected.
Autosomal dominant inheritance means that one affected parent (mother or father) has a 50% chance of passing the trait to a child; both sons and daughters are equally likely to be affected. Two affected people can have an unaffected child. Although it is likely that an affected person has an affected parent, there are exceptions: the affected person is the result of a new mutation; the parent transmitting the gene is an asymptomatic carrier; or the parent of the affected individual expressed the gene but in ways that were not readily recognized.
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