Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disorder stemming from several genetic mutations. The most characteristic feature of the disease is extraocular muscle weakness leading to ptosis and limited eye movements. Generalized weakness, cataracts, ataxia, depression, heart conduction abnormalities, and hearing loss are other notable manifestations of the disease. The diagnosis rests on a thorough clinical assessment followed by imaging and muscle biopsy studies. Molecular genetic testing for detection of mitochondrial DNA mutations is necessary for a confirmation of the diagnosis.
Chronic progressive external ophthalmoplegia (CPEO) is considered to be one of the diseases enclosed in the group of mitochondrial disorders in the adult population [1]. Various mutations in the mitochondrial DNA, either in a familial or sporadic pattern, present the underlying cause of the disease [2] [3]. CPEO is by some authors regarded as a part of the continuum of the mitochondrial myopathy disease spectrum, together with CPEO plus and Kearns-Sayre syndrome [4]. The clinical presentation develops as a result of progressive muscle weakness [1] [4]. Extraocular muscle weakness is the cardinal manifestation of chronic progressive external ophthalmoplegia, manifesting as bilateral ptosis and limited eye movements [5]. Cataracts can sometimes be observed [5]. In addition to ocular symptoms, mitochondrial DNA mutations affect other structures including the skeletal muscles, the retina, and the cerebellum [1]. Generalized fatigue and painful movements of the limbs is reported by the majority of patients, which may be severe enough to limit daily activities and significantly impair the quality of life [1]. These complaints are the probable reason why depression may be encountered, another important constituent of the clinical presentation of CPEO [1] [5]. Defects of the cerebellum and the vestibulocochlear system may lead to symptoms such as ataxia and hearing loss [1] [4] [5]. Heart conduction disorders are also reported in a significant number of cases and are the hallmarks of a more severe phenotype of the disease.
To make the diagnosis of a mitochondrial myopathy, the physician must perform a thorough clinical assessment, starting with a proper patient history. The onset of symptoms, their progression, as well as severity must be covered, as they can provide vital clues toward the diagnosis of myopathic disorders. When generalized weakness accompanied by muscle pain, ocular deficits, impaired coordination, and hearing loss are present, a more detailed investigation should be sought. An electrocardiogram (ECG) is useful for detecting heart conduction abnormalities. Imaging studies such as magnetic resonance imaging (MRI) of the head and MR spectroscopy may show atrophy of the cerebrum and cerebellum, as well as a reduced size of the extraocular muscles [4] [6] [7]. Nevertheless, these changes, although suggestive of mitochondrial myopathy, are not specific to CPEO [4]. For this reason, muscle biopsy and subsequent histopathological examination need to be performed [3] [5] [8] [9]. The biopsy will usually depict the presence of ragged red fibers and cytochrome c oxidase (COX)-deficient fibers, which are highly specific for a mitochondrial disease [5]. Approximately 25% of patients will have normal biopsy results, thus molecular genetic studies are considered to be the main method of confirming chronic progressive external ophthalmoplegia [3] [5] [8] [9].