Autosomal recessive progressive external ophthalmoplegia

What it is

From: Orphanet

A rare genetic, neuro-ophthalmological disease characterized by progressive weakness of the external eye muscles, resulting in bilateral ptosis and diffuse, symmetric ophthalmoparesis. Additional signs may include generalized skeletal muscle weakness, muscle atrophy, sensory axonal neuropathy, ataxia, cardiomyopathy, and psychiatric symptoms. It is usually more severe than autosomal dominant form.

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.

Cardiomyopathy · Frequent (79-30%)

A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.

Cytochrome C oxidase-negative muscle fibers · Frequent (79-30%)

An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue.

Dysphagia · Frequent (79-30%)

Difficulty in swallowing.

External ophthalmoplegia · Frequent (79-30%)

Paralysis of the external ocular muscles.

Facial palsy · Frequent (79-30%)

Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form.

Mask-like facies · Frequent (79-30%)

A lack of facial expression often with staring eyes and a slightly open mouth.

Mitochondrial myopathy · Frequent (79-30%)

A type of myopathy associated with mitochondrial disease and characterized by findings on biopsy such as ragged red muscle fibers.

Myopathy · Frequent (79-30%)

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

Paresthesia · Frequent (79-30%)

Abnormal sensations such as tingling, pricking, or numbness of the skin with no apparent physical cause.

Peripheral neuropathy · Frequent (79-30%)

Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.

Ragged-red muscle fibers · Frequent (79-30%)

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.

Sensory axonal neuropathy · Frequent (79-30%)

An axonal neuropathy of peripheral sensory nerves.

Abnormal cerebral white matter morphology · Occasional (29-5%)

An abnormality of the cerebral white matter.

Abnormal retinal morphology · Occasional (29-5%)

A structural abnormality of the retina.

Other findings in the same source

From: Orphanet

Additional reported features include Abnormality of the cerebrospinal fluid (Occasional (29-5%)); Action tremor (Occasional (29-5%)); Ataxia (Occasional (29-5%)); Bradykinesia (Occasional (29-5%)); Cerebellar atrophy (Occasional (29-5%)); Cerebral atrophy (Occasional (29-5%)); Cogwheel rigidity (Occasional (29-5%)); Depression (Occasional (29-5%)); Distal sensory impairment (Occasional (29-5%)); Dyschromatopsia (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

All ages

Inheritance in the source

From: Orphanet

Autosomal recessive

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Autosomal recessive progressive external ophthalmoplegia is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

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.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Autosomal recessive progressive external ophthalmoplegia. 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.