OMIM ID:
Oculopharyngeal Muscular Dystrophy
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Progressive ptosis is the cardinal ocular feature of this syndrome (present in at least 88% of patients). External ophthalmoparesis of some degree is often present with weakness of upgaze most common.
Systemic Features
This is a late onset form of progressive muscular dystrophy with onset of symptoms during midlife (mean age of onset ~48 years). Evidence of pharyngeal muscle weakness often occurs concomitantly with the ocular signs (43%). Ptosis occurs first in 43% and dysphagia first in 14%. Dysarthria and dysphagia are often associated with facial muscle weakness. Swallowing times for ice cold water and dry food is usually prolonged. Evidence of weakness and wasting of neck and limb muscles is usually noted later. Life expectancy is normal in contrast to some other forms of muscular dystrophy. Some patients have significant gait problems and generalized disability as a result of muscle weakness.
Microscopic studies of muscle biopsies usually show evidence of myopathy with abnormal fibers and accumulations of sarcoplasmic matter. Intranuclear inclusions consisting of tubular filaments and mitochondrial abnormalities have also been described. Serum CK can be significantly elevated in severe cases.
Genetics
Inheritance
This is an autosomal dominant disorder resulting from mutations in the PABPN1 gene located at 14q11.2-q13. Several patients with homozygous and compound heterozygous mutations have also been reported. The PABPN1 gene product is normally a facilitator of polyadenylation of mRNA molecules and may also be active in regulating mRNA production.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission