Autosomal dominant 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 skeletal muscle weakness, cataracts, hearing loss, sensory axonal neuropathy, ataxia, parkinsonism, cardiomyopathy, hypogonadism and depression. It is usually less severe than autosomal recessive 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.

External ophthalmoplegia · Very frequent (99-80%)

Paralysis of the external ocular muscles.

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).

Abnormality of eye movement · Frequent (79-30%)

An abnormality in voluntary or involuntary eye movements or their control.

Abnormality of the mitochondrion · Frequent (79-30%)

An anomaly of the mitochondrion, the membranous cytoplasmic organelle the interior of which is subdivided by cristae. The mitochondrion is a self replicating organelle that is the site of tissue respiration.

Bradykinesia · Frequent (79-30%)

Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).

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

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

EMG: myopathic abnormalities · Frequent (79-30%)

The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials.

Exercise intolerance · Frequent (79-30%)

A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender.

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.

Fatigue · Frequent (79-30%)

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

Hypomimic face · Frequent (79-30%)

A reduced degree of motion of the muscles beneath the skin of the face, often associated with reduced facial crease formation.

Limb muscle weakness · Frequent (79-30%)

Reduced strength and weakness of the muscles of the arms and legs.

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.

Other findings in the same source

From: Orphanet

Additional reported features include Ophthalmoparesis (Frequent (79-30%)); Ophthalmoplegia (Frequent (79-30%)); Quadriceps muscle weakness (Frequent (79-30%)); Ragged-red muscle fibers (Frequent (79-30%)); Resting tremor (Frequent (79-30%)); Shoulder girdle muscle weakness (Frequent (79-30%)); Abnormality of extrapyramidal motor function (Occasional (29-5%)); Anxiety (Occasional (29-5%)); Arrhythmia (Occasional (29-5%)); Ataxia (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Adolescent; Adult

Inheritance in the source

From: Orphanet

Autosomal dominant

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal dominant pattern means that one altered copy of a relevant gene can be sufficient for the condition. Some affected people inherit the change; others have a new change without an affected parent. The precise finding, family history and condition determine what this means for relatives.

Which doctor should you see?

The suggested department for discussing Autosomal dominant 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 dominant 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.