Progressive external ophthalmoplegia-myopathy-emaciation syndrome

What it is

From: Orphanet

Progressive external ophthalmoplegia-myopathy-emaciation syndrome is a rare mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies characterized by progressive external ophthalmoplegia without diplopia, cerebellar atrophy, proximal skeletal muscle weakness with generalized muscle wasting, profound emaciation, respiratory failure, spinal deformity and facial muscle weakness (manifesting with ptosis, dysphonia, dysphagia and nasal speech). Intellectual disability, gastrointestinal symptoms (e.g. nausea, abdominal fullness, and loss of appetite), dilated cardiomyopathy and renal colic have also been reported.

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.

Progressive external ophthalmoplegia · Very frequent (99-80%)

Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades.

Dilated cardiomyopathy · Frequent (79-30%)

Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to cause global systolic impairment. Right ventricular dilation and dysfunction may be present but are not necessary for the diagnosis.

Dysphagia · Frequent (79-30%)

Difficulty in swallowing.

Dysphonia · Frequent (79-30%)

Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause.

Dyspnea · Frequent (79-30%)

Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.

Easy fatigability · Frequent (79-30%)

Increased susceptibility to fatigue.

Elevated circulating creatine kinase concentration · Frequent (79-30%)

The activity of creatine kinase in the blood circulation is above the upper limit of normal.

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.

Generalized amyotrophy · Frequent (79-30%)

Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.

Hypernasal speech · Frequent (79-30%)

A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages.

Hyporeflexia · Frequent (79-30%)

Reduction of neurologic reflexes such as the knee-jerk reaction.

Kyphosis · Frequent (79-30%)

Exaggerated anterior convexity of the thoracic vertebral column.

Myopathy · Frequent (79-30%)

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

Nausea · Frequent (79-30%)

A sensation of unease in the stomach together with an urge to vomit.

Other findings in the same source

From: Orphanet

Additional reported features include Ptosis (Frequent (79-30%)); Ragged-red muscle fibers (Frequent (79-30%)); Recurrent infections (Frequent (79-30%)); Respiratory failure (Frequent (79-30%)); Spinal deformities (Frequent (79-30%)); Spinal rigidity (Frequent (79-30%)); Weakness of facial musculature (Frequent (79-30%)); Decreased mitochondrial number (Frequent (79-30%)); Nephrolithiasis (Occasional (29-5%)); Poor appetite (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

Frequency and the population described

From: Orphanet

Reported case(s): 6.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

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 Progressive external ophthalmoplegia-myopathy-emaciation syndrome 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 Progressive external ophthalmoplegia-myopathy-emaciation syndrome. 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.