SNP Shot: Genomic Insights

Oculopharyngeal muscular dystrophy (OPMD) is an inherited disorder characterized by progressive muscle weakness, typically starting after age 40. The name reflects the primary areas affected: the eyes ("oculo-") and the pharynx ("-pharyngeal"), which is part of the throat. A common initial symptom is ptosis, or drooping eyelids, affecting both eyes. As ptosis progresses, it can obstruct vision and potentially limit eye movement. In addition to ptosis, individuals develop dysphagia, or difficulty swallowing, due to weakness in the throat muscles. Initially, dysphagia affects the ability to swallow dry foods, but it can eventually extend to liquids. This swallowing difficulty can lead to saliva buildup and a voice that sounds wet. Weakness and atrophy (wasting) of the tongue are also common. These feeding problems can result in malnutrition, choking, or aspiration pneumonia, a bacterial lung infection caused by inhaling food or saliva.

OPMD often involves weakness in the proximal muscles, those located near the body's center, especially in the shoulders, upper legs, and hips (the limb-girdle muscles). This weakness gradually worsens, potentially requiring the use of a cane or walker for mobility. In rare instances, wheelchair assistance becomes necessary.

In rare cases, individuals experience a more severe form of OPMD, with muscle weakness onsetting before age 45 and loss of independent walking ability by age 60. These individuals may also develop neuropathy (nerve dysfunction), cognitive decline (a gradual loss of intellectual abilities), and psychiatric symptoms such as depression or delusions (strongly held false beliefs).

Inheritance:

OPMD is usually inherited in an autosomal dominant manner. This means that having just one copy of the mutated gene in each cell is enough to cause the condition. However, some individuals inherit mutations in both copies of the PABPN1 gene, resulting in expanded polyalanine tracts. These individuals tend to experience more severe symptoms that appear earlier in life compared to those with only one mutated gene copy. In most autosomal dominant cases, an affected person has inherited the mutated gene from one parent who also has the condition.