Oculopharyngeal Muscular Dystrophy (OPMD) is a rare, inherited disorder that causes progressive weakness in specific muscles, primarily affecting those around the eyes and in the throat. Symptoms usually begin in adulthood, most often between the ages of 40 and 60 years old. The progression of muscle weakness is generally slow, but it can significantly diminish a person’s quality of life as it interferes with fundamental activities like seeing and swallowing. Understanding what happens to someone with OPMD involves examining the molecular cause, the initial physical effects, the systemic progression of muscle loss, and the current methods used to manage the resulting challenges.
The Genetic Basis of OPMD
The underlying cause of OPMD is a genetic change within the PABPN1 gene, which provides instructions for making the Polyadenylate-Binding Protein Nuclear 1. A non-pathogenic version of this gene contains a sequence of ten GCN trinucleotide repeats, which code for a chain of ten alanine amino acids. In an individual with OPMD, this sequence is abnormally expanded, typically containing 11 to 18 GCN repeats.
This expansion results in the production of an altered PABPN1 protein that contains an elongated polyalanine tract. The mutated protein does not function correctly and becomes insoluble, leading to its accumulation and clumping into structures known as intranuclear inclusions within the nuclei of muscle cells. This protein aggregation is thought to impair the normal function of the muscle cells, causing them to weaken and eventually die off.
Primary Physical Manifestations
The weakening of the levator palpebrae superioris muscle in the upper eyelid causes a condition called ptosis, or drooping eyelids. This drooping is often symmetrical and can become severe enough to partially cover the pupil, which obstructs the field of vision and makes daily activities difficult.
To compensate for the drooping eyelids, people often instinctively tilt their head backward or overuse their forehead muscles in an attempt to see clearly. The second hallmark symptom is dysphagia, or difficulty swallowing, which is caused by the progressive weakness of the pharyngeal muscles in the throat. Initially, this problem may only involve dry or solid foods, which feel stuck or require extra effort to pass.
As the pharyngeal muscles continue to weaken, the risk of food or liquid entering the airway instead of the esophagus, a process called aspiration, increases significantly. This aspiration can lead to frequent coughing, choking episodes, and potentially life-threatening aspiration pneumonia.
Secondary and Systemic Progression
Weakness in the proximal limb muscles, particularly those in the shoulders and hips, is common and typically begins years after the onset of ptosis and dysphagia. This weakness can alter a person’s gait, making walking and climbing stairs progressively more challenging, with some individuals eventually requiring a cane, walker, or, in rare cases, a wheelchair.
Weakness in the pharyngeal and tongue muscles also causes changes in communication and oral hygiene. The voice may become noticeably wet or gurgling, a condition known as dysphonia, due to the pooling of saliva that the weakened muscles struggle to clear. Furthermore, the persistent difficulty with swallowing can lead to serious nutritional impacts, including unintended weight loss, chronic dehydration, and malnutrition.
Current Approaches to Managing Symptoms
The focus of medical care is on managing the symptoms to maintain function and quality of life. For drooping eyelids, non-surgical options include specialized eyeglasses fitted with thin metal attachments, known as ptosis crutches, that mechanically hold the eyelids open. If the drooping severely impairs vision, surgical correction procedures, such as levator muscle shortening or frontal suspension, may be performed by an ophthalmologist.
Managing dysphagia is a high priority and often involves a multidisciplinary approach, starting with speech-language pathology. Therapists teach specific swallowing techniques and recommend dietary modifications, such as altering food textures and using liquid thickeners, to make meals safer. When swallowing becomes severely compromised, a surgical procedure called cricopharyngeal myotomy may be performed to widen the opening of the upper esophageal sphincter. In the most advanced stages, a feeding tube, such as a percutaneous endoscopic gastrostomy (PEG), may become necessary to ensure adequate nutrition and hydration.