The clinical presentation of patients suffering from Kearns Sayre syndrome (KSS), in which spontaneous deletion of mitochondrial DNA occurs during embryogenesis, is quite specific and is comprised of a juvenile onset (before 20 years of age), progressive external ophthalmoplegia (PEO) and pigmentary retinopathy [1] [2]. Several other features are frequently encountered, one of the most common being cardiac conduction abnormalities - left anterior fascicular block (with or without right bundle branch block), various degrees of atrioventricular (AV) block, long QT wave, torsades de pointes type of ventricular tachycardia and dilated cardiomyopathy are diagnosed in 50% of cases [3] [4]. Sudden cardiac death preceded by syncope is seen in up to 20% of patients, stressing the need for an early diagnosis [4]. Additionally, almost 40% of KSS patients have a short stature [5], while hearing loss, dementia, dysphagia, weakness of the limbs and ataxia originating from the cerebellum are additional symptoms [1] [2] [6]. Diabetes mellitus is an important endocrinopathy encountered in a significant proportion of patients, whereas thyroid and parathyroid abnormalities, as well as Addison's disease and growth hormone deficiency, have been observed in KSS [2] [7]. Intolerance to exercise can be reported by many patients, and because of the wide spectrum of signs and symptoms that may be noted, the diagnosis is often delayed for a significant period of time [1] [7].

A detailed diagnostic workup is pivotal in order to make the diagnosis of KSS, especially when the presence of cardiac abnormalities can predispose to sudden cardiac arrest. Firstly, patient history should reveal the onset and course of symptoms, as young age is considered as mandatory criteria for KSS. A thorough physical examination, if conducted properly, can detect ataxia, arrhythmias, ptosis, visual deficits, hearing loss and weakness of the limbs. Ophthalmoscopy must be carried out to confirm retinal changes and ophthalmoplegia, while cardiac assessment must not be forgotten, and electrocardiography (ECG), as well as cardiac ultrasonography, are essential if KSS is suspected [1]. However, a definite diagnosis is achieved through laboratory testing that notes very high levels of lactate and pyruvate in blood, especially after moderate exercise, abnormally high protein content in the cerebrospinal fluid (more than 100mg/dL), and markedly reduced activity of enzymes involved in the respiratory chain complex, such as citrate synthase [1]. Clinical and biochemical suspicion toward KSS is confirmed by performing a muscle biopsy, which will reveal typical "ragged-red fibers" (RRFs) on gömöri trichrome stain, hyperactive fibers when using the succinate dehydrogenase stain and failure to stain both RRF and non-RRF fibers using cytochrome c oxidase (COX) [6] [7].

There is no cure for Kearns-Sayre Syndrome, but treatment focuses on managing symptoms and preventing complications. Regular monitoring by a multidisciplinary team, including cardiologists, neurologists, and ophthalmologists, is essential. Pacemakers may be required for heart block, and cochlear implants can help with hearing loss. Physical therapy and occupational therapy can assist with muscle weakness and coordination issues. Supplements such as coenzyme Q10 and antioxidants may be recommended to support mitochondrial function, although their effectiveness varies.

The prognosis for individuals with Kearns-Sayre Syndrome varies depending on the severity of symptoms and the presence of complications. Early diagnosis and management can improve quality of life and extend life expectancy. However, the progressive nature of the disease means that symptoms may worsen over time, and some patients may develop life-threatening complications, particularly related to cardiac issues.

Kearns-Sayre Syndrome is caused by deletions in mitochondrial DNA. Mitochondria have their own DNA, separate from the nuclear DNA, and mutations in this mitochondrial DNA can disrupt the normal production of energy in cells. These deletions are usually sporadic, meaning they occur randomly and are not inherited from parents. However, in rare cases, KSS can be passed down through maternal inheritance.

Kearns-Sayre Syndrome is a rare condition, with an estimated prevalence of 1 to 3 cases per 100,000 individuals. It affects both males and females equally and typically presents before the age of 20. Due to its rarity, KSS may be underdiagnosed or misdiagnosed, especially in its early stages.

The pathophysiology of Kearns-Sayre Syndrome involves defects in the mitochondria, which are responsible for producing energy in the form of adenosine triphosphate (ATP). The deletions in mitochondrial DNA impair the function of the electron transport chain, a critical component of ATP production. This energy deficit particularly affects tissues with high energy demands, such as muscles, the heart, and the nervous system, leading to the characteristic symptoms of KSS.

Currently, there is no known way to prevent Kearns-Sayre Syndrome, as the genetic mutations occur spontaneously. Genetic counseling may be beneficial for families with a history of mitochondrial disorders to understand the risks and implications of the disease. Ongoing research into mitochondrial diseases may provide insights into potential preventive strategies in the future.

Kearns-Sayre Syndrome is a rare mitochondrial disorder characterized by eye muscle weakness, retinal degeneration, and heart block, among other symptoms. Diagnosis involves clinical evaluation and genetic testing, while treatment focuses on symptom management. Although there is no cure, early intervention can improve outcomes. The disease is caused by deletions in mitochondrial DNA, and its rarity makes it a challenge to diagnose and study.

If you or a loved one has been diagnosed with Kearns-Sayre Syndrome, it is important to work closely with a healthcare team to manage symptoms and monitor for complications. Regular check-ups with specialists, including cardiologists and neurologists, are crucial. While living with KSS can be challenging, support from healthcare providers, family, and patient advocacy groups can help improve quality of life.

1. DiMauro S, Hirano M. Mitochondrial DNA Deletion Syndromes. 2003 Dec 17 [Updated 2011 May 3]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews. Seattle (WA): University of Washington, Seattle; 1993-2016.
2. Laloi-Michelin M, Virally M, Jardel C, et al. Kearns Sayre syndrome: an unusual form of mitochondrial diabetes. Diabetes Metab. 2006;32(2):182-186.
3. Obara-Moszynska M, Maceluch J, Bobkowski W, et al. A novel mitochondrial DNA deletion in a patient with Kearns-Sayre syndrome: a late-onset of the fatal cardiac conduction deficit and cardiomyopathy accompanying long-term rGH treatment. BMC Pediatr. 2013;13:27.
4. Van Beynum I, Morava E, Taher M, et al. Cardiac Arrest in Kearns–Sayre Syndrome. JIMD Rep. 2012;2:7-10.
5. Holloman CM, Wolfe LA, Gahl WA, Boerkoel CF. Kearns-Sayre syndrome presenting as isolated growth failure. BMJ case rep. 2013;2013:10.1136/bcr-2012-007272 bcr2012007272.
6. 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.
7. Leal M, Dhoble C, Lee J, Lopez D, Menéndez LS. A rare case of Kearns–Sayre syndrome in a 17-year-old Venezuelan male with bilateral ptosis as the initial presentation. Oxf Med Case Reports. 2016;2016(3):34-36.