Oculopharyngeal Muscular Dystrophy

Oculopharyngeal muscular dystrophy is a late onset autosomal dominant disorder caused by GCN repeat expansion in PABPN1, with ptosis, dysphagia and proximal limb weakness. Onset is usually in the fifth to sixth decade. Prevalence is about 1 in 100,000, and higher in French Canadians, Bukhara Jews and Hispanic New Mexicans.

Pathophysiology. The expanded polyalanine tract causes nuclear aggregates of mutant protein in muscle fibres, with impaired mRNA processing.

Progressive bilateral ptosis, then dysphagia (solids first), dysphonia, tongue weakness, facial weakness, proximal limb weakness (leg more than arm) and sometimes ophthalmoparesis. Weight loss and aspiration pneumonia occur. Severe cases cause loss of walking. Cognition is normal.

Red flags.

• Aspiration pneumonia or significant weight loss.
• Ptosis blocking vision.

Genetic testing for PABPN1 GCN expansion (more than 10 repeats; 11 to 17 in dominant disease) confirms the diagnosis. Creatine kinase is normal or mildly raised. Electromyography is myopathic. Muscle biopsy shows rimmed vacuoles and intranuclear filaments. Videofluoroscopy assesses swallowing. Muscle MRI shows tongue and proximal leg involvement.

Differential diagnosis.

• Myasthenia gravis, mitochondrial myopathy with progressive external ophthalmoplegia.
• Inclusion body myositis, myotonic dystrophy and thyroid eye disease.
• Motor neuron disease with bulbar onset and Kearns-Sayre syndrome.

Ptosis. Ptosis crutches, or surgery (levator resection or frontalis sling) to improve the visual field. Recurrence is common.

Dysphagia. Speech therapy, modified diet and textures, swallowing manoeuvres, and cricopharyngeal myotomy for severe dysphagia (benefits swallowing for several years). Gastrostomy when oral intake is unsafe.

Weakness. Physiotherapy, mobility aids and falls prevention.

Respiratory. Treat aspiration, and vaccinate.

Genetic counselling. Offer to family members.

Monitoring. Weight, swallowing, vision and mobility yearly.

Referral and escalation. Refer to neuromuscular, otolaryngology and ophthalmology services.

Special groups. Surgery and anaesthesia need planning because of swallowing risks.