What is KSS?

Kearns-Sayre syndrome (KSS) is a mitochondrial DNA deletion syndrome that impacts multiple systems of the body. It is a rare disorder, affecting an estimated 1.6 out of 100,000 individuals[1]. Males and females are affected in equal numbers.

Classical Kearns-Sayre syndrome is defined by three features [1,2]:

  1. weakness of the eye muscles (chronic progressive external ophthalmoplegia (CPEO) and droopy eyelids (ptosis)
  2. degeneration of the pigmented cell layer in the back of the eye (pigmentary retinopathy)
  3. cardiac conduction block

In addition, patients often develop difficulty swallowing, nasal speech, limb muscle weakness, and incoordination (ataxia). KSS gradually worsens over time. Unfortunately, no one has identified a means of stopping KSS, and prognosis depends on disease severity. However, many individuals with the disorder may live well into adulthood[2]. Early diagnosis and interventions that address some of the symptoms of KSS may be particularly helpful in this regard.

What causes KSS?

KSS is caused by large deletions of mitochondrial DNA. The specific size and sequence of DNA deleted varies from individual to individual; however, many have a 5 kilobase deletion (the ‘common deletion’).

In approximately 90% of KSS cases, the deletions have appeared by chance[3]. Inheritance of a KSS-causing mutation is extremely rare; a woman with CPEO or KSS with a single mtDNA deletion may transmit the mutation to about 4% of their children.

What are the symptoms of KSS?

Chronic progressive external ophthalmoplegia (CPEO) is one of the key features of KSS. Its symptoms include:

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

Additional key feature of KSS are: degeneration of the pigmented cell layer in the back of the eye (pigmentary retinopathy) and cardiac conduction block.

KSS also often includes following manifestations[4]:

  • difficulty swallowing and limb muscle weakness often accompany the eye abnormalities
  • elevated cerebrospinal fluid (CSF) protein
  • incoordination (ataxia)
  • depression
  • impaired cognition

Kearns-Sayre patients usually have multi-organ system involvement and may suffer from some of the mitochondrial problems depicted in Figure 1 (image coming soon) (4) .

In particular, individuals with KSS may have[5,6]:

  • short stature
  • failure to thrive
  • hearing loss
  • folate deficiency
  • diminished muscle tone (hypotonia)
  • delayed puberty
  • intellectual disability
  • seizures
  • diabetes and other endocrine problems
  • renal impairment

How do I know if my loved one has KSS?

KSS diagnosis is based on clinical features accompanied by the presence of a mitochondrial DNA deletion.

If you or your loved one shows signs of KSS, their healthcare provider may perform the following to establish a diagnosis:

  • a muscle sample (biopsy) or buccal swab to look for mitochondrial DNA deletion (A muscle biopsy can confirm mitochondrial abnormalities on microscopic study)
  • an echocardiogram
  • ophthalmological examination
  • measurements of the level of lactic acid and pyruvate in the blood
  • an electrocardiogram
  • an electromyogram
  • a brain MRI
  • hearing test
  • blood tests to check for evidence of mitochondrial dysfunction, endocrinopathies (especially diabetes and growth hormone deficiency), and kidney dysfunction.
  • measurements of the level of protein in the cerebrospinal fluid (CSF)

What are the treatments for KSS?

Options for managing KSS symptoms include:

  • surgery or special glasses to correct drooping eyelids
  • physical and occupational therapy to improve muscle strength and balance
  • a pacemaker for heart conduction block
  • a cochlear implant for hearing problems
  • folinic acid for cerebral folate deficiency
  • hormone replacement for short stature
  • insulin for diabetes
  • supplements such as coenzyme Q10, B complex vitamins, alpha lipoic acid, or L-carnitine

Regular checkups with specialists are critical for those with KSS. Monitoring for signs of heart problems is particularly important since sudden cardiac events, in particular cardiac conduction block are a common cause of death in these individuals[6]. Onset of slow heart rate, heart racing, or fainting spells require an urgent emergency room visit.

Are there any clinical trials for KSS?

Currently KSS clinical trials focus on exercise intolerance (generally patients with CPEO+ and not classical KSS).

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 KSS families.

How can my family cope with KSS?

We are here to help. UMDF serves a number of families coping with KSS. 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,  KSS specific support meetings, and more. They’ll also connect you with a UMDF ambassador, likely a fellow KSS patient or family member, who can help support and guide you through your questions.

 

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

  • 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 KSS 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 KSS 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 KSS?

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

  • Research & Funding: UMDF has provided more than $14 million in research funding to find treatments for diseases like KSS. 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 KSS. 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 KSS, 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. Remes AM, Majamaa-Voltti K, Kärppä M, et al. Prevalence of large-scale mitochondrial DNA deletions in an adult Finnish population. Neurology. 2005;64(6):976-981. doi:10.1212/01.WNL.0000154518.31302.ED
  1. https://www.omim.org/entry/530000
  1. Björkman K, Vissing J, Østergaard E, et al. Phenotypic spectrum and clinical course of single large-scale mitochondrial DNA deletion disease in the paediatric population: a multicentre study [published online ahead of print, 2021 Dec 6]. J Med Genet. 2021;jmedgenet-2021-108006. doi:10.1136/jmedgenet-2021-108006
  1. Gorman GS, Chinnery PF, DiMauro S, Hirano M, Koga Y, McFarland R, Suomalainen A, Thorburn DR, Zeviani M, Turnbull DM. 2016 Mitochondrial diseases. Nat Rev Dis Primers. 2016 Oct 20;2:16080
  1. Shemesh A, Margolin E. Kearns Sayre Syndrome. [Updated 2021 Aug 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482341/
  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. Grady JP, Campbell G, Ratnaike T, et al. Disease progression in patients with single, large-scale mitochondrial DNA deletions. Brain. 2014;137(Pt 2):323-334. doi:10.1093/brain/awt321
  1. Khambatta S, Nguyen DL, Beckman TJ, Wittich CM. Kearns-Sayre syndrome: a case series of 35 adults and children. Int J Gen Med. 2014;7:325-332. Published 2014 Jul 3. doi:10.2147/IJGM.S65560