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chronic_progressive_external_ophthalmoplegia [2026/09/08 12:33] – Scott Larsonchronic_progressive_external_ophthalmoplegia [2026/09/08 12:40] (current) – Scott Larson
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 ===== Overview ===== ===== Overview =====
  
-**CPEO** is a **mitochondrial myopathy** that predominantly affects the extraocular muscles and the levator palpebrae, producing slowly progressive, generally **symmetric ophthalmoparesis** and **ptosis**. Because progression is gradual and symmetric, patients frequently do **not** report diplopia (<30%) and may be unaware of their motility deficit, often adopting a compensatory chin-up head posture ((mcclelland))((mcfarland)).+**CPEO** is a **mitochondrial myopathy** that predominantly affects the extraocular muscles and the levator palpebrae, producing slowly progressive, generally **symmetric ophthalmoparesis** and **ptosis**. Because progression is gradual and symmetric, patients frequently do **not** report diplopia (<30%) and may be unaware of their motility deficit, often adopting a compensatory chin-up head posture.
  
 ===== Onset and Course ===== ===== Onset and Course =====
  
-  * Typical onset in **adulthood** (commonly 18–40 years), with **ptosis** often the first sign ((mcfarland)). +  * Typical onset in **adulthood** (commonly 18–40 years), with **ptosis** often the first sign. 
-  * **Slowly progressive** over years; forced ductions are free (myopathic, not restrictive) and **pupils are spared** ((mcclelland)). +  * **Slowly progressive** over years; forced ductions are free (myopathic, not restrictive) and **pupils are spared**. 
-  * **"CPEO-plus"** phenotypes add systemic features: pigmentary retinopathy, cerebellar ataxia, peripheral neuropathy, sensorineural hearing loss, cardiac conduction block, and diabetes. The combination of early-onset PEO, pigmentary retinopathy, and cardiac conduction disease defines **Kearns-Sayre syndrome** ((mcfarland))((ng)).+  * **"CPEO-plus"**: pigmentary retinopathy, cerebellar ataxia, peripheral neuropathy, sensorineural hearing loss, cardiac conduction block, and diabetes.  
 +  * **Kearns-Sayre syndrome** defined as early-onset ophthalmoplegia and ptosis, pigmentary retinopathy, and cardiac conduction disease.
  
 ===== Genetics ===== ===== Genetics =====
  
-  * Most commonly caused by a **single large-scale mtDNA deletion** (sporadic), but also by **mtDNA point mutations** and **nuclear mtDNA-maintenance genes** (e.g., **POLG, RRM2B, TWNK**) ((li))((mcfarland)). +  * Most commonly caused by a **single large-scale mtDNA deletion** (sporadic), but also by **mtDNA point mutations** and **nuclear mtDNA-maintenance genes** (e.g., **POLG, RRM2B, TWNK**). 
-  * **Heteroplasmy** matters: mutant load is far higher in skeletal muscle than in blood, so **negative peripheral blood testing does not exclude CPEO** ((li))((mcfarland)).+  * **Heteroplasmy** matters: mutant load is far higher in skeletal muscle than in blood, so **negative peripheral blood testing does not exclude CPEO**.
  
 ===== Diagnostic Evaluation ===== ===== Diagnostic Evaluation =====
  
-  * **Clinical eye and systemic exam** — motility, lids, pupils, dilated fundus, cardiac review ((mcclelland)). +  * **Clinical eye and systemic exam** — motility, lids, pupils, dilated fundus, cardiac review. 
-  * **Screening labs** — resting/post-exercise lactate and pyruvate, lactate:pyruvate ratio, creatine kinase, glucose/HbA1c; plus **ECG** given conduction-block risk ((gorman)). +  * **Screening labs** — resting/post-exercise lactate and pyruvate, lactate:pyruvate ratio, creatine kinase, glucose/HbA1c; plus **ECG** given conduction-block risk. 
-  * **Exclude mimics** — myasthenia gravis (AChR/MuSK antibodies), oculopharyngeal and myotonic dystrophy ((ng)). +  * **Exclude mimics** — myasthenia gravis (AChR/MuSK antibodies), oculopharyngeal and myotonic dystrophy. 
-  * **Muscle biopsy** (most accurate single test) — **ragged-red fibers** (Gomori trichrome) and **COX-negative / SDH-hyperintense fibers**; also enables respiratory-chain enzyme assays ((rodriguez)). +  * **Muscle biopsy** (most accurate single test) — **ragged-red fibers** (Gomori trichrome) and **COX-negative / SDH-hyperintense fibers**; also enables respiratory-chain enzyme assays. 
-  * **Genetic testing** — whole mtDNA sequencing plus long-range PCR for deletions; **muscle is the optimal tissue**; nuclear gene panels when multiple deletions/depletion or a familial pattern is present ((gorman))((rodriguez)).+  * **Genetic testing** — whole mtDNA sequencing plus long-range PCR for deletions; **muscle is the optimal tissue**; nuclear gene panels when multiple deletions/depletion or a familial pattern is present.
  
 ===== Key Points ===== ===== Key Points =====
  
   * No blood test is confirmatory; diagnosis is **clinical + histochemical + genetic**.   * No blood test is confirmatory; diagnosis is **clinical + histochemical + genetic**.
-  * A **negative blood mtDNA test does not rule out** the disease — proceed to muscle if suspicion is high ((li)). +  * A **negative blood mtDNA test does not rule out** the disease — proceed to muscle if suspicion is high. 
-  * Screen for and monitor **cardiac conduction disease**, a source of preventable morbidity/mortality ((mcfarland)).+  * Screen for and monitor **cardiac conduction disease**, a source of preventable morbidity/mortality.
  
 ====Compare CPEO with Congenital Fibrosis of EOM (CFEOM)==== ====Compare CPEO with Congenital Fibrosis of EOM (CFEOM)====