What is CPEO “plus”?

Chronic progressive external ophthalmoplegia “plus” (CPEO “plus”) is a mitochondrial DNA deletion syndrome that affects the eye plus at least one other organ or system. It is sometimes called “Kearns-Sayre syndrome (KSS)-spectrum” due to the fact that it involves symptoms beyond CPEO but is less severe than classical KSS[1].

The age of onset of the condition is usually 20 or more[1]. The progression of the disease varies greatly among individuals[2]. Prognosis depends on disease severity.

Treatments for CPEO “plus” focus on symptom management and can improve an affected individual’s quality of life.

What causes CPEO “plus”?

CPEO “plus” has the same cause as CPEO: mitochondrial DNA deletions.

These deletions may arise from a mutation in one of the following nuclear genes[1,3]:

  • POLG
  • OPA1
  • RRM2B
  • TWNK
  • SLC25A
  • DNA2

Alternatively, the deletions can arise from a single point mutation in the mitochondrial gene MT-TL1[1].

These mutations can either be inherited or appear by chance in individuals with no family history of CPEO “plus”.

What are the symptoms of CPEO “plus”?

Eye problems caused by CPEO “plus” are[1]:

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

CPEO “plus” also includes at least one of the following[1]:

  • hearing loss
  • loss of sensation in the limbs
  • impaired muscle coordination
  • movement abnormalities including Parkinsonism
  • depression (mood disorders)

How do I know if my loved one has CPEO “plus”?

If your loved one has symptoms of CPEO and other symptoms, their healthcare provider will look for mitochondrial DNA deletion in a muscle sample (biopsy). They will also carefully consider the additional symptoms to diagnose CPEO “plus” vs. KSS.


What are the treatments for CPEO “plus”?

Treatments for CPEO “plus” may consist of[1]:

  • surgery or special glasses to correct drooping eyelids
  • physical and occupational therapy to address limb weakness
  • hearing aids for hearing loss
  • vitamins such as coenzyme Q10 or L-carnitine for general benefit (reference)

Are there any clinical trials for CPEO “plus”?

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

How can my family cope with CPEO “plus”?

We are here to help. UMDF serves many families coping with CPEO “plus”. 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, disease or region specific support meetings, and more. They’ll also connect you with a UMDF ambassador, likely a fellow CPEO “plus” patient or family member, who can help support and guide you through your questions.

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

  • Get Support
    Connect with our Support & Education Team online, via email at support@umdf.org or phone at (888) 900-6486.
  • Check our Clinical Trials Finder
    Use our Clinical Trials Finder to see if you qualify for any clinical trials.
  • Join our patient registry, mitoSHARE
    We are actively recruiting CPEO “plus” 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 “plus” 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 so you – and your friends and family – can let Congress know where we need their support. Click here to sign up.

What is UMDF doing about CPEO “plus”?

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

  • Research & Funding: UMDF has provided more than $15 million in research funding to find treatments for diseases like CPEO “plus”. 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.

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.


  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