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.
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”.
- 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)
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.
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.
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.
- Join the conversation online
– UMDF Social Media Support Groups: Facebook Support Group
– UMDF News & Updates: Facebook | Twitter | Instagram | YouTube
- Get involved
Join the fight by giving your voice, generosity, time or energy. Click here to see how you can help.
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.
- Patient Support: Thousands of families just like you depend upon UMDF for support and education on diseases like CPEO “plus”. Attendance at our support meetings annually tops 7,000, including disease specific support meetings for MELAS families.
- Clinician Support: To help educate clinicians on diseases like CPEO “plus”, 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.
- 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/
- 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
- Van Goethem G, Martin JJ, Van Broeckhoven C. Progressive external ophthalmoplegia characterized by multiple deletions of mitochondrial DNA: unraveling the pathogenesis of human mitochondrial DNA instability and the initiation of a genetic classification. Neuromolecular Med. 2003;3(3):129-146. doi:10.1385/NMM:3:3:129
