What is CPEO?

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial DNA deletion syndrome characterized by weakness of the eye muscles.

The condition typically emerges in adults between the ages of 18 and 40(3). Symptoms tend to worsen over time although the exact course of the disease varies greatly among individuals(3,4,5). Treatments can address some of the symptoms, and individuals with isolated CPEO generally have a normal life expectancy.

What causes CPEO?

Most cases of CPEO are caused by mitochondrial DNA deletions. Most are sporadic without involvement of other family members and allow risk of transmission to an offspring. These deletions may arise from a mutation in a nuclear gene that has been associated with CPEO including (6,7):
  • POLG
  • POLG2
  • TK2
  • OPA1
  • RRM2B
  • TWNK
  • SLC25A
  • RRM1
  • TOP3A
  • C1QBP
  • DNA2
  • C10ORF2
  • DGUOK
  • MPV17
  • MGME1
  • SPG7
  • AFG3L2
  • RNASEH1
  • GMPR
Less commonly, CPEO may be caused by single point mutations in the mitochondrial gene such as the MT-TL1 m.3243A>G variant which also causes mitochondrial encephalomyopathy lactic acidosis stroke-like episodes (MELAS).

These mutations can be either inherited or appear by chance in individuals with no family history of CPEO. Single mtDNA deletions typically arise spontaneously, but women who are symptomatic with single mtDNA can transmit the mutation to 4% of their children. By contrast, point mutations of mtDNA are generally transmitted from mothers to all of their children. Mutations in nuclear genes are transmitted in autosomal dominant, recessive, or X-linked patterns depending upon the particular gene.

What are the symptoms of CPEO?

The symptoms of CPEO are:

  • drooping eyelids (ptosis)
  • paralysis of the muscles that control eye movement
  • impaired swallowing
  • weakness of the limbs

CPEO may also be associated with hearing loss, loss of sensation in the limbs, impaired muscle coordination, movement abnormalities, cardiac conduction block, or depression. In these cases, the disorder is referred to as progressive external ophthalmoplegia plus (PEO+)[1].

How do I know if my loved one has CPEO?

If your loved one has symptoms of CPEO, their healthcare provider will look for mitochondrial DNA deletion in a muscle sample (biopsy) or a buccal swab to help establish a diagnosis.

What are the treatments for CPEO?

Treatments for CPEO may consist of:

  • surgery or special glasses to correct drooping eyelids
  • physical and occupational therapy to address limb weakness

Are there any clinical trials for CPEO?

At this time, clinical trials for CPEO are focused on exercise intolerance and muscle weakness.

To see what trials you may qualify for, visit our Clinical Trials page – which also included a Clinical Trials Finder Tool. We also highly encourage you to join our patient registry, mitoSHARE, where we are actively recruiting CPEO families.

How can my family cope with CPEO?

We are here to help. UMDF serves a number of families coping with CPEO. We suggest you reach out to our Support & Education Team – online, via email at support@umdf.org or phone at (888) 900-6486 – who can suggest a host of resources including doctors, CPEO specific support meetings, and more. They’ll also connect you with a UMDF ambassador, likely a fellow CPEO patient or family member, who can help support and guide you through your questions.

 

A Patient Perspective:

I have lived with CPEO for over 20 years. I learned early on how to manage symptoms to give myself the highest quality of life. In CPEO the eyelid does not close all the way and is weak. This results in the eyeball not getting the proper protection and in turn, this can cause visual disturbances (blurry and double vision, severe dry eyes.) The good news is that with a proper daily regimen, a person can improve and help their eyes. Before I knew and started my regiment, I had developed ulcers on my cornea. Since taking proactive measures, I have had none. The following are suggestions to help the environment of the eyes when living with CPEO:

  • Tear duct plugs – help keep the moisture in the eye and an eye doctor can put them in, only takes a minute.
  • Tape eyes shut each night – in the morning no more waking up with dry scratchy eyes. 1 inch 3MM surgical foam tape applied to each eye before going to sleep. Place an eye lubricant in each eye first. Then tear off about 3 inches from the roll of tape and secure the eyelid downwards (like you are pulling it down and into place.) The 3-inch tape should be horizontally placed.
  • Daily use of eye lubricant drops.
  • Restasis RX eye drops daily.
  • Warm compresses on each eye when waking in the morning.
  • Extra thick eye lubricant or gel eye drops when eyes are extra dry.
  • Frontalis Sling surgery consult with an Oculoplastic Surgeon specializing in lid lifts to see if you are a candidate. Lifting the eyelids can be a game-changer enabling a better line of sight.
  • Protective eyewear when outside, to shield from wind and sun.
  • Check for clinical trials through the UMDF for muscle weakness – mitochondrial myopathies.

The above is not medical advice it is what I have learned to help manage my CPEO symptoms over the years. For my muscle weakness, I do physical therapy three times weekly.

*Please note this is one patient’s perspective, not medical advice. We encourage you to consult with your physician or specialist before taking any action.

What are the next steps if my loved one has CPEO?

  • Get Support
    Connect with our Support & Education Team online, via email at support@umdf.org or phone at (888) 900-6486.
  • Join our patient registry, mitoSHARE
    We are actively recruiting CPEO families to participate in our patient registry, mitoSHARE. Patient registries like mitoSHARE are an integral part in charting a course toward treatments and cures for CPEO and other mitochondrial diseases. There are currently over 30 active mitochondrial disease clinical trials. Next generation patient registries like mitoSHARE are an integral part of expanding that number.
  • Become an advocate
    Ask your representatives to prioritize mitochondrial disease research and support via the UMDF Advocacy Center. We’ll send regular action items where you – and your friends and family – can let Congress know we need their support. Click here to sign up.

What is UMDF doing about CPEO?

UMDF is helping chart a path toward treatments and eventual cure of mitochondrial diseases like CPEO through:

  • Research & Funding: UMDF has provided more than $14 million in research funding to find treatments for diseases like CPEO. UMDF advocacy has helped secure an additional $55 million in federal funding via the Department of Defense and National Institutes of Health.
  • Data: Over two decades ago, UMDF pioneered patient registries for the mitochondrial disease community. Today, our next generation patient registry, mitoSHARE, is helping chart a path toward the treatment and eventual cure of mitochondrial diseases.
  • Patient Support: Thousands of families just like you depend upon UMDF for support and education on diseases like CPEO. Attendance at our support meetings annually tops 7,000, including disease specific support meetings for families.
  • Clinician Support: To help educate clinicians on diseases like CPEO, we feature monthly Bench to Bedside clinician seminars, host the annual Mitochondrial Medicine Symposium, support the Mitochondrial Care Network, and educate clinicians on our Mito U platform.

I didn’t find what I’m looking for here. What should I do?

UMDF is here to help. Contact the Support Line at (888) 900-6486 weekdays from 8:00am to 5:00pm EST to connect with our Patient Concierge. Or, via email contact support@umdf.org.

References

  1. Emmanuele V, Ganesh J, Vladutiu G, Haas R, Kerr D, Saneto RP, Cohen BH, Van Hove JLK, Scaglia F, Hoppel C, Rosales XQ, Barca E, Buchsbaum R, Thompson JL, DiMauro S, Hirano M, North American Mitochondrial Disease C. Time to harmonize mitochondrial syndrome nomenclature and classification: A consensus from the North American Mitochondrial Disease Consortium (NAMDC). Mol Genet Metab. 2022;136(2):125-31.
  1. Mancuso M, Orsucci D, Angelini C, Bertini E, Carelli V, Comi GP, Donati MA, Federico A, Minetti C, Moggio M, Mongini T, Santorelli FM, Servidei S, Tonin P, Toscano A, Bruno C, Bello L, Caldarazzo Ienco E, Cardaioli E, Catteruccia M, Da Pozzo P, Filosto M, Lamperti C, Moroni I, Musumeci O, Pegoraro E, Ronchi D, Sauchelli D, Scarpelli M, Sciacco M, Valentino ML, Vercelli L, Zeviani M, Siciliano G.J Redefining phenotypes associated with mitochondrial DNA single deletion. Neurol. 2015 May;262(5):1301-9.
  1. Goldstein A, Falk MJ. Mitochondrial DNA Deletion Syndromes. 2003 Dec 17 [Updated 2019 Jan 31]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1203/
  1. 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. doi:10.1093/brain/awm067
  1. Lopez-Gomez C, Camara Y, Hirano M, Marti R. 232nd ENMC international workshop: Recommendations for treatment of mitochondrial DNA maintenance disorders. 16 – 18 June 2017, Heemskerk, The Netherlands. Neuromuscul Disord. 2022 in press.
  1. Sommerville EW, Chinnery PF, Gorman GS, Taylor RW. Adult-onset Mendelian PEO Associated with Mitochondrial Disease. J Neuromuscul Dis. 2014;1(2):119-133.