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.
Presentation
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.
Eyes
- Retinal Lesion
On the basis of a detailed study of the literature we can conclude that the retinal lesions in chronic progressive external ophthalmoplegia may vary from benign pigmentations without functional impairment to genuine 'retinitis pigmentosa' with all gradations [ncbi.nlm.nih.gov]
Musculoskeletal
- Myopathy
In conclusion, mitochondrial myopathy was definitely diagnosed. [ncbi.nlm.nih.gov]
To make the diagnosis of a mitochondrial myopathy, the physician must perform a thorough clinical assessment, starting with a proper patient history. [symptoma.com]
- Neck Muscle Weakness
Before the treatment, except bilateral ptosis and external ophthalmopelgia, this patient presented bulbar muscle weakness and neck muscle weakness. [ncbi.nlm.nih.gov]
- Neck Weakness
low BMI, leukoencephalopathy and depression 11 43 None 30% COX deficient/5% RRF LRPCR c.556A>G and c.653C>T p.Arg186Gly and p.Thr218Ile 6 and 6 No 21 PEO, ptosis, facial weakness, tongue weakness, neck weakness, SNHL, dysphagia, proximal muscle weakness [doi.org]
Neurologic
- Average Intelligence
The patient was born of consanguineous parents, developed normally, and was of average intelligence. [ncbi.nlm.nih.gov]
Workup
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].
Treatment
There is currently no defined treatment to ameliorate the muscle weakness of CPEO. Treatments used to treat other pathologies causing ophthalmoplegia has not been shown to be effective. [en.wikipedia.org]
Diseases that induce chronic progressive external ophthalmoplegia require specific treatment. [ic.steadyhealth.com]
[…] for CPEO and treatment is mainly symptomatic. – Surgical treatment of severe ptosis can be beneficial in patients with CPEO. [entokey.com]
Effective treatment does not exist, and corrective surgery of the ptosis as a palliative measure is a treatment option. This was a retrospective study of 10 years' duration gathering patients with the diagnosis. [ncbi.nlm.nih.gov]
Prognosis
Therefore, we suggest that C10orf2 gene should be screened in CPEO individuals with multiple mtDNA deletions, which might help in prognosis of this disease and appropriate genetic counseling. [ncbi.nlm.nih.gov]
Prognosis Luckily, people with CPEO have a good prognosis and the disease should not effect other aspects of health. While the disease is progressive and symptoms tend to get worse over time, the severity of the disease differs with each patient. [healthguideinfo.com]
The MTTL1 gene is most often associated with the mitochondrial inheritance pattern, along with other mtRNA and mtDNA genes. [14] Prognosis The prognosis is guarded with a generally progressive disorder. [emedicine.com]
KSS is slowly progressive and prognosis varies depending on severity and the number of systems or organs involved which widely varies from patient to patient. [umdf.org]
Etiology
Significant pain, proptosis, or pupil involvement are not features of CPEO and should prompt evaluation for alternative etiologies. Mitochondrial DNA mutations are increasingly being recognized as the etiology for CPEO syndromes. [ncbi.nlm.nih.gov]
In both cases, hematological studies and neuroimaging ruled out alternative etiologies, whereas muscle biopsy showed findings of mitochondrial myopathy. No Reference information available - sign in for access. [ingentaconnect.com]
Applicable To Progressive external ophthalmoplegia with pigmentary retinopathy Use Additional Use Additional Help Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10data.com]
Epidemiology
April 2014 Volume 55, Issue 13 Free ARVO Annual Meeting Abstract | April 2014 A national epidemiological study of chronic progressive external ophthalmoplegia in the United Kingdom - molecular genetic features and neurological burden Author Affiliations [iovs.arvojournals.org]
MeSH terms, Substance MeSH terms Adult Audiometry, Pure-Tone DNA, Mitochondrial/genetics Evoked Potentials, Auditory Female Gene Deletion Hearing Loss, Sensorineural/epidemiology* Hearing Loss, Sensorineural/etiology* Hearing Loss, Sensorineural/physiopathology [ncbi.nlm.nih.gov]
Alpha-1 antitrypsin deficiency (AAT deficiency) Definition : a congenital disorder characterized by the accumulation of defective alpha-1 antitrypsin enzyme Epidemiology : more common in individuals of European descent [1] Etiology : mutations in SERPINA1 [amboss.com]
EPIDEMIOLOGY Incidence CPEO typically have an onset in childhood or early adolescence but they can occur at any age. [entokey.com]
Diagnosis: Chronic Progressive External Ophthalmoplegia (CPEO) - Kearns Sayre Syndrome EPIDEMIOLOGY Rare cause of chronic ptosis + ophthalmoplegia Usually present in 2nd decade of life SIGNS Ptosis with poor levator function Loss of Bell’s reflex (eyes [webeye.ophth.uiowa.edu]
Pathophysiology
Definition : a congenital disorder characterized by the accumulation of defective alpha-1 antitrypsin enzyme Epidemiology : more common in individuals of European descent [1] Etiology : mutations in SERPINA1 gene [1] Inheritance : autosomal codominant Pathophysiology [amboss.com]
Article navigation 1 1 Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy Search for other [doi.org]
PATHOPHYSIOLOGY • The mitochondria is responsible for production of ATP by oxidative phosphorylation, the detoxification of reactive oxygen species, regulation of cell apoptosis, and other functions such iron metabolism, fatty acid oxidation, and amino [entokey.com]
Pathophysiology Mitochondrial DNA (mtDNA) encodes for essential components of the respiratory chain. [emedicine.com]
Prevention
A thorough ophthalmic history and examination before ptosis surgery may prevent the corneal complications resulting from surgical intervention. [ncbi.nlm.nih.gov]
Research is ongoing to develop a way to prevent the transmission of mitochondrial DNA mutations to future children. [mda.org.au]
Prevention There is no way to prevent ophthalmoplegia. Resources Organizations American Academy of Neurology. 1080 Montreal Ave., St. Paul, MN 55116. (612) 695-1940. http://www.aan.com. [medical-dictionary.thefreedictionary.com]
Are these tumors related to the MERRF and is there any way to try and prevent their growth? Speaker_-_Dr__Sumit_Parikh: Fatty tumors (lipomas) can be seen more commonly in certain mitochondrial disorders. There is no way to prevent these. [my.clevelandclinic.org]
References
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- Auré K. Ogier de Baulny H, Laforêt P, Jardel C, Eymard B, Lombès A. Chronic progressive ophthalmoplegia with large-scale mtDNA rearrangement: can we predict progression? Brain. 2007;130(Pt 6):1516-1524.
- Wabbels B, Ali N, Kunz WS, Roggenkämper P, Kornblum C. Chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome : interdisciplinary diagnosis and therapy [Article in German] Ophthalmologe. 2008;105(6):550-556.
- Heidenreich JO, Klopstock T, Schirmer T, Saemann P, Mueller-Felber W, Auer DP. Chronic progressive external ophthalmoplegia: MR spectroscopy and MR diffusion studies in the brain. AJR Am J Roentgenol. 2006;187(3):820-824.
- Chen T, Pu C, Shi Q, et al. Chronic progressive external ophthalmoplegia with inflammatory myopathy. Int J Clin Exp Pathol. 2014;7(12):8887-8892.
- Wray SH, Provenzale JM, Johns DR, et al. MR of the brain in mitochondrial myopathy. Am J Neuroradiol 1995;16:1167-1173.
- Carlow TJ, Depper MH, Orrison WW. MR of extraocular muscles in chronic progressive external ophthalmoplegia. Am J Neuroradiol 1998;19:95-99.
- Kornblum C, Kunz WS, Klockgether T, Roggenkämper P, Schröder R. Diagnostic value of mitochondrial DNA analysis in chronic progressive external ophthalmoplegia (CPEO) [Article in German] Klin Monbl Augenheilkd. 2004;221(12):1057-1061.
- Sundaram C, Meena AK, Uppin MS, et al. Contribution of muscle biopsy and genetics to the diagnosis of chronic progressive external opthalmoplegia of mitochondrial origin. J Clin Neurosci. 2011;18(4):535-538.