Chronic Progressive External Ophthalmoplegia

abbreviated CPEO

Onset Adult, typically 18–40 yrs; ptosis first sign [5-6] Congenital / present at birth [2, 7] Course Slowly progressive over years [1, 5] Non-progressive (rare exceptions) [4] Symmetry / gaze Generally symmetric, diffuse limitation of all directions; superior rectus often prominently involved [8-9] Fixed characteristic pattern — CFEOM1: eyes fixed in infraduction, absent upgaze; CFEOM2: large-angle exotropia [7, 10] Ptosis Common, may be uni- or bilateral, progressive [5] Congenital, typically bilateral; chin-up head posture [2, 7] Diplopia Usually absent (<30%) due to gradual symmetric onset [11] Absent; binocular vision typically never develops [2] Pupils Spared Spared in CFEOM1; poorly reactive in CFEOM2 [10] Inheritance / genetics Single large-scale mtDNA deletion (~50%, sporadic); also nuclear mtDNA-maintenance genes (POLG, RRM2B, TWNK) and mtDNA point mutations [6, 12] Mendelian: CFEOM1 (AD, KIF21A); CFEOM2 (AR, PHOX2A); CFEOM3 (AD, TUBB3/TUBB2B/TUBA1A/KIF21A) [10, 13] Systemic/associated features “CPEO-plus”: retinopathy, ataxia, neuropathy, deafness, cardiac conduction block, diabetes (Kearns-Sayre) [8, 14] Usually isolated; CFEOM3 may have developmental/CNS anomalies (e.g., Tukel syndrome) [10] Muscle biopsy Ragged-red / COX-negative fibers; mitochondrial abnormalities [5] Not a mitochondrial biopsy diagnosis; muscle shows fibrosis/denervation changes [7] Orbital MRI Mild EOM atrophy with fatty/spongiform T1 signal [4, 9] EOM hypoplasia + hypoplastic ocular motor nerves [2, 10]