Dysphagia usually follows ptosis by a few years, although it may precede ptosis in some patients. It tends to be more severe for solids than for liquids and can be assessed with a simple bedside test. A time for swallowing 80 mL ice-cold water >7 s is considered positive for dysphagia. Nasal regurgitation is often present as the disease progresses. Untreated, dysphagia may lead to choking, aspiration pneumonia, and cachexia. It is a significant cause of morbidity and mortality in OPMD patients.

As the disease progresses, other muscle groups may become involved. Extraocular movements may become limited, especially for upward gaze. When present, horizontal gaze limitation is often discrete. Diplopia is usually not a complaint because of the slowly progressive course of the disease.

Limb–girdle weakness is eventually noted in over two-thirds of patients, and more frequently involves the lower than the upper extremities. In a study of 72 patients, proximal lower limb weakness was found in 71% of patients and upper extremity weakness in 38% of patients. Lower limb weakness is often limited to hip flexion, although hip abduction, adduction, and extension may be involved as the disease progresses. Upper limb weakness tends to involve the deltoid and biceps muscles more prominently. A large percentage of patients will use either a cane or a walker late in the course of the disease. The occasional, more severely affected patient will require a wheelchair, mainly to cover long distances.

Among other clinical features, weakness of facial muscles (43%), weakness and/or atrophy of the tongue (82%), and voice changes such as hoarseness and hypernasality due to palatal weakness (67%) may be observed.

The disease has a slowly progressive course and life expectancy is not diminished when swallowing is managed appropriately. With progress in the treatment of dysphagia, prognosis and quality of life are much improved.

Homozygotes for OPMD (children of two carrier parents) have been reported and compared with their heterozygote siblings. The onset of symptoms is on average 18 years earlier, the disease progresses faster, and death usually occurs in the sixth decade. In addition, cognitive decline, psychotic episodes, and depression are observed in homozygote patients.

Epidemiology

Although OPMD has now been reported in over 35 countries, a founder effect is responsible for a high prevalence of OPMD in the province of Québec (Canada) where the prevalence is estimated at 1 in 1000. A higher concentration of cases is also seen in the south-western states of the USA as well as in Bukhara Jews living in Israel.

Diagnosis

The diagnosis of OPMD can be easily confirmed by genetic testing. It is caused by variable size expansion of GCG triplets coding for alanine in a gene called polyadenylation-binding protein nuclear 1 (PABPN1) (Brais 2003). The test has 99% sensitivity and specificity, and is available in many commercial laboratories worldwide. A point mutation in the first exon of the gene may account for cases without GCG triplet expansion, so sequencing of the first exon may be ordered when the diagnosis is strongly suspected on clinical grounds, but the genetic test for PABPN1 expansions is negative.

A rarer recessive form allelic to the dominantly inherited OPMD has also been reported with either a milder or a more severe phenotype.

Although OPMD is caused by triplet expansions, there is no correlation between expansion size and age of onset or severity of clinical manifestations. Unlike myotonic dystrophy, another triplet repeat disease, there is no anticipation through generations as the expansion size is mitotically stable.

With genetic testing readily available, muscle biopsy is not indicated. If performed, rimmed vacuoles and intranuclear inclusions are the two main abnormalities observed. Rimmed vacuoles are readily detected by light microscopy but are not specific, being observed in other myopathies, mainly inclusion body myositis. Electron microscopy shows the intranuclear inclusions comprising tubular filaments. Other nonspecific findings that are common to many muscular dystrophies are atrophied, small, angulated, muscle fibers, type 1 fiber predominance, variation in fiber size, degenerating and regenerating fibers, and an increased percentage of internal nuclei.