Oculopharyngeal muscular dystrophy

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Oculopharyngeal muscular dystrophy is a genetic condition characterized by muscle weakness that begins in adulthood, typically after age 40. The term "oculopharyngeal" refers to the eyes (oculo-) and a part of the throat called the pharynx (-pharyngeal). Affected individuals usually first experience weakness of the muscles in both eyelids that causes droopy eyelids (ptosis). Ptosis can worsen over time, causing the eyelid to impair vision, and in some cases, limit eye movement. Along with ptosis, affected individuals develop weakness of the throat muscles that causes difficulty swallowing (dysphagia). Dysphagia begins with dry food, but over time, liquids can also become difficult to swallow. Dysphagia can cause saliva to accumulate and a wet-sounding voice. Many people with oculopharyngeal muscular dystrophy also have weakness and wasting (atrophy) of the tongue. These problems with food intake may cause malnutrition, choking, or a bacterial lung infection called aspiration pneumonia.

Individuals with oculopharyngeal muscular dystrophy frequently have weakness in the muscles near the center of the body (proximal muscles), particularly muscles in the shoulders, upper legs, and hips (limb-girdle muscles). The weakness slowly gets worse, and people may need the aid of a cane or a walker. Rarely, affected individuals need wheelchair assistance.

Rarely, individuals have a severe form of oculopharyngeal muscular dystrophy with muscle weakness that begins before age 45, and have trouble walking independently by age 60. These individuals often also have disturbances in nerve function (neuropathy), a gradual loss of intellectual functioning (cognitive decline), and psychiatric symptoms such as depression or strongly held false beliefs (delusions).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the PABPN1 gene cause oculopharyngeal muscular dystrophy. The PABPN1 gene provides instructions for making a protein that is found throughout the body. The PABPN1 protein plays an important role in processing molecules called messenger RNAs (mRNAs), which serve as genetic blueprints for making proteins. PABPN1 alters a region at the end of mRNA molecules that protects mRNA from being broken down. The PABPN1 protein also is involved in transporting mRNA within the cell.

The PABPN1 protein contains an area where 10 copies of the protein building block (amino acid) alanine occur in a row. This stretch of alanines is known as a polyalanine tract. The role of the polyalanine tract in normal PABPN1 protein function is unknown. Mutations in the PABPN1 gene that cause oculopharyngeal muscular dystrophy result in a PABPN1 protein with an abnormally long (extended) polyalanine tract that includes between 11 and 18 alanines. Typically, affected individuals with shorter polyalanine tracts tend to have milder signs and symptoms that develop later in life compared to those with longer polyalanine tracts. The extra alanines cause the PABPN1 protein to form nonfunctional clumps within muscle cells. These clumps (called intranuclear inclusions) accumulate and are thought to impair the normal functioning of muscle cells, eventually causing cell death. The resulting loss of muscle cells over time most likely causes the muscle weakness seen in people with oculopharyngeal muscular dystrophy. In severe cases, it is likely that intranuclear inclusions affect nerve cells as well as muscle cells.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Most cases of oculopharyngeal muscular dystrophy are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, some individuals have mutations in both copies of the PABPN1 gene that lead to expanded polyalanine tracts. These individuals tend to have more severe signs and symptoms that develop earlier in life compared to individuals with a mutation in one copy of the gene.

In most cases, an affected person has one parent with the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

In Europe, the prevalence of oculopharyngeal muscular dystrophy is estimated to be 1 in 100,000 people. This condition is much more common in the French-Canadian population of the Canadian province of Quebec, where it is estimated to affect 1 in 1,000 individuals. Oculopharyngeal muscular dystrophy is also seen more frequently in the Bukaran Jewish population of Israel, affecting 1 in 700 people.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal muscle fiber morphology · Very frequent (99-80%)

Any abnormality of the skeletal muscle cell. Muscle fibers are subdivided into two types. Type I fibers are fatigue-resistant and rich in oxidative enzymes (they stain light with the myosin ATPase reaction), and type II fibers are fast-contracting, fatigue-prone, and rich in glycolytic enzymes (these fibers stain darkly). Normal muscle tissue has a random distribution of type I and type II fibers.

Dysphagia · Very frequent (99-80%)

Difficulty in swallowing.

Fatigue · Very frequent (99-80%)

A subjective feeling of tiredness characterized by a lack of energy and motivation.

Myopathy · Very frequent (99-80%)

A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.

Ophthalmoplegia · Very frequent (99-80%)

Paralysis of one or more extraocular muscles that are responsible for eye movements.

Ptosis · Very frequent (99-80%)

The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Ragged-red muscle fibers · Very frequent (99-80%)

An abnormal appearance of muscle fibers observed on muscle biopsy. Ragged red fibers can be visualized with Gomori trichrome staining as irregular and intensely red subsarcolemmal zones, whereas the normal myofibrils are green. The margins of affect fibers appear red and ragged. The ragged-red is due to the accumulation of abnormal mitochondria below the plasma membrane of the muscle fiber, leading to the appearance of a red rim and speckled sarcoplasm.

Rimmed vacuoles · Very frequent (99-80%)

Presence of abnormal vacuoles (membrane-bound organelles) in the sarcolemma. On histological staining with hematoxylin and eosin, rimmed vacuoles are popcorn-like clear vacuoles with a densely blue rim. The vacuoles are often associated with cytoplasmic and occasionally intranuclear eosinophilic inclusions.

Other findings in the same source

From: Orphanet

Additional reported features include Spondylolisthesis (Very frequent (99-80%)); Angulated muscle fibers (Frequent (79-30%)); Axial muscle weakness (Frequent (79-30%)); Dysphonia (Frequent (79-30%)); Fatty replacement of skeletal muscle (Frequent (79-30%)); Feeding difficulties (Frequent (79-30%)); Limb-girdle muscle weakness (Frequent (79-30%)); Muscle fiber intranuclear inclusion bodies (Frequent (79-30%)); Pain (Frequent (79-30%)); Reduced forced expiratory volume in one second (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Oculopharyngeal muscular dystrophy is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Oculopharyngeal muscular dystrophy. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.