What is oculopharyngeal muscular dystrophy (OPMD)?

From the Guidelines

Oculopharyngeal muscular dystrophy (OPMD) is a rare genetic disorder characterized by progressive muscle weakness, primarily affecting the eyelids and throat, and can be associated with upper oesophageal sphincter disturbances, including disordered neurally mediated opening of the upper oesophageal sphincter, as noted in the 2018 UK guidelines on oesophageal dilatation in clinical practice 1. Key characteristics of OPMD include:

• Progressive muscle weakness, primarily affecting the eyelids and throat
• Symptoms of dysphagia due to upper oesophageal sphincter disturbances
• Potential for treatment with upper oesophageal sphincter dilatation to relieve symptoms, as recommended in the 2018 guidelines with a moderate GRADE of evidence and strong strength of recommendation 1
• No cure, but treatment focuses on managing symptoms and maintaining quality of life Management strategies for OPMD may include:

1. Speech therapy: To improve swallowing and reduce the risk of aspiration
2. Eyelid surgery (blepharoplasty): For severe eyelid drooping (ptosis) that impairs vision
3. Swallowing interventions: Including modified diets, chin tuck maneuver while swallowing, or in severe cases, feeding tube placement
4. Physical therapy: To maintain muscle strength and mobility
5. Regular monitoring: For progression of symptoms and potential complications It is essential to note that OPMD is caused by a mutation in the PABPN1 gene, leading to abnormal protein accumulation in muscle cells, resulting in gradual muscle weakness and atrophy, typically starting in adulthood and progressing slowly over decades 1. Patients with OPMD should be advised to:

• Eat slowly and carefully to prevent choking
• Maintain good nutrition and hydration
• Stay physically active within their capabilities
• Have regular check-ups with a neurologist and other specialists as needed Understanding the genetic basis of OPMD helps in diagnosis and genetic counseling for affected families, and the 2018 guidelines provide a foundation for managing symptoms and improving quality of life for patients with OPMD 1.

From the Research

Definition and Characteristics of Oculopharyngeal Muscular Dystrophy (OPMD)

• Oculopharyngeal muscular dystrophy (OPMD) is a late-onset intractable myopathy characterized by slowly progressive ptosis, dysphagia, and proximal limb weakness 2.
• It is caused by the abnormal expansion of the alanine-encoding (GCN)n trinucleotide repeat in the exon 1 of the polyadenosine (poly[A]) binding protein nuclear 1 gene (11-18 repeats in OPMD instead of the normal 10 repeats) 2, 3.
• OPMD is an autosomal dominant form of late-onset muscular dystrophy, with ptosis and dysphagia being the most common presenting symptoms 4.

Symptoms and Progression

• As the disease progresses, patients gradually develop a feeling of suffocation, regurgitation of food, and aspiration pneumonia, although the initial symptoms and the progression patterns vary among patients 2.
• The symptoms of OPMD include ptosis, dysphagia, and limb weakness, which can significantly impact health-related quality of life (HRQoL) 5.
• Lower extremity functional impairment and dysphagia symptom severity are significant predictors of HRQoL in OPMD patients 5.

Treatment and Management

• Autologous myoblast transplantation may provide therapeutic benefits by reducing swallowing problems in OPMD patients 2.
• Gene therapy combining complete knockdown of endogenous PABPN1 and its replacement by a wild-type PABPN1 has shown promise in reducing muscle fibrosis and improving muscle strength in a mouse model of OPMD 3.
• There is a need for more sensitive measures of OPMD progression, including biomarkers that do not require a muscle biopsy, to monitor disease progression and assess treatment efficacy 6.