[Skip to Content]
[Skip to Content Landing]
September 1993

Ocular Clinicopathologic Study of the Mitochondrial Encephalomyopathy Overlap Syndromes

Author Affiliations

From the Eye Pathology Laboratory, Wilmer Institute, and Department of Pathology (Drs Chang, Walker, and Green and Ms de la Cruz), the Center for Hereditary Eye Diseases, Wilmer Institute (Dr Maumenee), and the Department of Neurology (Dr Johns), The Johns Hopkins Medical Institutions, Baltimore, Md. Dr Walker is now with the Ophthalmology Department, University of British Columbia, Vancouver.

Arch Ophthalmol. 1993;111(9):1254-1262. doi:10.1001/archopht.1993.01090090106028

Recent advances in molecular genetics have led to a better understanding of mitochondrially inherited diseases. Mitochondrial encephalomyopathy overlap syndrome is one such group of diseases in which ocular abnormalities are frequently manifest. The authors describe the clinical, molecular genetic, and pathologic findings of two patients with the mitochondrial encephalomyopathy overlap syndrome. The patients shared a similar clinical course with features overlapping the three traditionally distinct clinical phenotypes (the Kearns-Sayre syndrome; the syndrome of mitochondrial encephalopathy, lactic acidosis, and stroke [MELAS], and the syndrome of myoclonus, epilepsy, and ragged red fibers [MERRF]). The patients had identical mitochondrial DNA mutations (at nucleotide position 3243) and had similar ultrastructural abnormalities, including abundant enlarged mitochondria with "whorled" and "tubular" cristae. These abnormal mitochondria appeared to be preferentially distributed in cells with high metabolic activity (retinal pigment epithelium, corneal endothelium, and extraocular muscles).

Kearns TP, Sayre GP.  Retinitis pigmentosa, external ophthalmoplegia and complete heart-block; unusual syndrome with histologic study in one of two cases . Arch Ophthalmol . 1958;60:280-289.Article
Kearns TP.  External ophthalmoplegia, pigmentary degeneration of the retina, and cardiomyopathy: a newly recognized syndrome . Trans Am Ophthalmol Soc . 1965;63:559-625.
Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP.  Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: a distinctive clinical syndrome . Ann Neurol . 1984;16:481-488.Article
Fukuhara N.  Myocolonus epilepsy and mitochondrial myopathy . In: Cerri C, Scarlato G, eds. Mitochondrial Pathology in Muscle Diseases . Padua, Italy: Piccin Editore; 1983:87-111.
Zupanc ML, Moraes CT, Shanske S, Langman CB, Ciafaloni E, DiMauro S.  Deletion of mitochondrial DNA in patients with combined features of Kearns-Sayre and MELAS syndromes . Ann Neurol . 1991;29:680-683.Article
Johns DR, Hurko O.  Mitochondrial leucine tRNA mutation in neurological diseases . Lancet . 1991;337:927-928.Article
Ciafaloni E, Ricci E, Shanske S, et al.  MELAS: clinical features, biochemistry, and molecular genetics . Ann Neurol . 1992;31:391-398.Article
Moraes CT, Ricci E, Bonilla E, DiMauro S, Schon E.  The mitochondrial tRNALeu(UUR) mutation in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS): genetic, biochemical, and morphological correlations in skeletal muscle . Am J Hum Genet . 1992;50:934-949.
Goto Y, Horai S, Matsuoka T, et al.  Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): a correlative study of the clinical features and mitochondrial DNA mutation . Neurology . 1992;43:545-550.Article
Hubner G, Gokel JM, Pongratz D, et al.  Fatal mitochondrial cardiomyopathy in Kearns-Sayre syndrome . Virchows Arch Pathol Anat . 1986;408:611-621.Article
Jager BV, Fred GL, Butler RB, Carnes WG.  Occurrence of retinal pigmentation, ophthalmoplegia, ataxia, deafness and heart block: report of a case, with findings at autopsy . Am J Med . 1960;29:888-893.Article
Daroff RB, Solitare GB, Pincus JH, Glaser GH.  Spongiform encephalopathy with chronic progressive external ophthalmoplegia . Neurology . 1966;16:161-169.Article
Horwitz SJ, Roessmann U.  Kearns-Sayre syndrome with hypoparathyroidism . Ann Neurol . 1978;3:513-518.Article
Newell FW, Polascik MA.  Mitochondrial disease and retinal pigmentary degeneration . In: Proceedings of the 23rd International Congress of Ophthalmology, Kyoto, Japan . New York, NY: Elsevier Science Publishing Co Inc; 1979;1:615-617.
Eagle RC, Hedges TR, Yanoff M.  The atypical pigmentary retinopathy of Kearns-Sayre syndrome: a light and electron microscopic study . Ophthalmology . 1982;89:1433-1440.Article
Eagle RC, Hedges TR, Yanoff M.  The Kearns-Sayre syndrome: a light and electron microscopic study . Trans Am Ophthalmol Soc . 1982;80:318-234.
McKechnie NM, King M, Lee WR.  Retinal pathology in the Kearns-Sayre syndrome . Br J Ophthalmol . 1985;69:63-75.Article
Flynn JT, Bachynski BN, Rodrigues MM, et al.  Hyperglycemic acidotic coma and death in Kearns-Sayre syndrome . Trans Am Ophthalmol Soc . 1985;83:131-161.
Runge P, Calver D, Marshal J, Taylor D.  Histopathology of mitochondrial cytopathy and the Laurence-Moon-Biedl syndrome . Br J Ophthalmol . 1986;70:782-796.Article
Morse PH, MacLean AL.  Fluorescein fundus studies in hereditary vitelliruptive macular degeneration . Am J Ophthalmol . 1968;66:485-494.