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].

• Short Stature

  Other findings in the syndrome may include muscle weakness, short stature, hearing loss, and the loss of ability to coordinate voluntary movements (ataxia) due to problems in the part of the brain called the cerebellum. [rxlist.com]

  Additionally, almost 40% of KSS patients have a short stature, while hearing loss, dementia, dysphagia, weakness of the limbs and ataxia originating from the cerebellum are additional symptoms. [symptoma.com]

  KSS has also been associated with a variety of endocrine and metabolic disorders, in particular short stature, gonadal failure, diabetes mellitus, thyroid disease, hyperaldosteronism, hypomagnesaemia, and bone, tooth and calcification abnormalities. [ncbi.nlm.nih.gov]

  This report focuses on the diagnosis of Kearns- Sayre syndrome in a Chinese girl who presented initially with short stature, delayed puberty, insidious onset of ptosis and later with typical features of Kearns-Sayre syndrome including complete heart block [hkmj.org]

• Progressive Ophthalmoplegia

  Kearns Sayre syndrome belongs to a group of mitochondrial DNA deletion syndromes, together with pearson syndrome and progressive external ophthalmoplegia (PEO). [symptoma.com]

  The syndrome is characterized by chronic progressive external ophthalmoplegia, tapetoretinal degeneration, and severe generalized myopathy. [ncbi.nlm.nih.gov]

  The Kearns-Sayre syndrome (KSS), consisting of progressive external ophthalmoplegia, ptosis, atypical pigment retinopathy, and cardiac conduction defects, is one of a diverse group of mitochondrial disorders that may be predominantly myopathic or involve [neurology.org]

  Kearns, American ophthalmologist, born 1922; George Pomeroy Sayre, American pathologist, born 1911] see under syndrome … Medical dictionary Kearns-Sayre syndrome — noun Oculocraniosomatic disease … Wiktionary Kearns-Sayre syndrome — progressive ophthalmoplegia [dic.academic.ru]

• Heart Disease

  disease (cardiomyopathy) such as cardiac conduction defects and heart block. [rxlist.com]

  The potential symptoms involved with KSS are wide-ranging and may include: Ataxia Diabetes Deafness Myopathy Heart block Hearing loss Short stature Heart disease Small sex organs Muscle weakness Endocrine disorders Retinal pigmentation Paralysis of eye [disabled-world.com]

  SECTION I-G: PACING IN CHILDREN, ADOLESCENTS, AND PATIENTS WITH CONGENITAL HEART DISEASE Recommendations for Permanent Pacing in Children, Adolescents, and Patients With Congenital Heart Disease Class I Class I Class I 1. [doi.org]

• Hearing Impairment

  Audiological evaluation revealed hearing impairment in 10/17 patients. [ncbi.nlm.nih.gov]

  The disease also can cause hearing impairment and short stature. [mda.org]

  Case presentation We report the case of an 18-year-old Romanian man with short stature, external ophthalmoplegia, palpebral ptosis, myopathy, sensorineural hearing impairment, cerebellar ataxia, cardiac conduction defect, diabetes mellitus, hypoparathyroidism [jmedicalcasereports.biomedcentral.com]

  Maternally inherited hearing impairment. Clin Genet. 2000 Jun;57(6):409-14. Review. Wallace DC. Mitochondrial diseases in man and mouse. Science. 1999 Mar 5;283(5407):1482-8. Review. [ghr.nlm.nih.gov]

• Retinal Pigmentation

  Other features include: cardiac conduction defects 4 retinal pigmentation ptosis The disease is characterized by the ragged-red appearance of muscle fibers, and the presence of mitochondrial DNA (mtDNA) with large deletions in affected tissues. [radiopaedia.org]

  The triad of progressive external ophthalmoplegia, atypical retinal pigmentation and cardiac conduction defects characterizes Kearns-Sayre syndrome (KSS), which is most often caused by a single, large deletion of mitochondrial DNA. [ncbi.nlm.nih.gov]

  Furthermore, in pigmentary retinopathy, there is a diffuse depigmentation of the retinal pigment epithelium with a characteristic mottled “salt-and-pepper” pattern of pigment clumping, in contrast to “Bone spicule” pigment formation in retinitis pigmentosa [statpearls.com]

  pigment epithelium and choriocapillaris. [8] Our patient had unusual retinal lesions in the right eye. [ojoonline.org]

• Blepharoptosis

  A 16-year-old patient suffering from Kearns-Sayre syndrome presented with severe blepharoptosis. A levator advancement procedure was performed. [ncbi.nlm.nih.gov]

  In this case, A 21-year-old man diagnosed with KSS, and presented with chronic progressive blepharoptosis (ptosis) and external ophthalmoplegia, diffuse depigmentation of the retinal pigment epithelium, and cerebellar ataxia, with a cerebrospinal fluid [nsj.org.sa]

  Keywords: Kearns-Sayre syndrome, blepharoptosis, fascia lata lid suspension, chronic progressive external ophthalmoplegia This work is published and licensed by Dove Medical Press Limited. [dovepress.com]

  We assume an autosomal-dominant inheritance, the marker sign of which is blepharoptosis in several family members. [karger.com]

  Frontalis suspension sling using a silicone rod in patients affected by myogenic blepharoptosis. Orbit. 2002 Sep;21(3):195-8. Brodsky MC, et al. Pediatric Neuro-Ophthalmology. New York: Springer, 1996. Esmaeli B, Chung H, Pashby RC. [webeye.ophth.uiowa.edu]

• Myopathy

  There are many other names for the Kearns-Sayre syndrome including: CPEO with myopathy; CPEO with ragged-red fibers; KSS; Mitochondrial cytopathy, Kearns-Sayre type; Oculocraniosomatic syndrome; Ophthalmoplegia-plus syndrome; Ophthalmoplegia with myopathy [rxlist.com]

  From Wikidata Jump to navigation Jump to search spontaneous occuring or inherited mitochondrial myopathy with a typical onset before 20 years of age Kearns-Sayre syndrome (disorder) Cpeo With Myopathy KSS Mitochondrial Cytopathy Cpeo With Ragged-Red Fibers [wikidata.org]

  W.L.: Ocular myopathy associated with Retinitis Pigmentosa. A.M.A. Arch. Ophth. 1957, 57:335-338. 4. Saudifer. P.H. : Chr.Progressive Ophthalmoplegia of Myopathic Origin. J. Neurol. Neurosurg and Psychiat. 1946. 9:81-83. 5. [ijo.in]

  Recruiting NCT04641962 Phase 2, Phase 3 Bocidelpar;Placebo 5 A Phase 3 Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Daily Subcutaneous Injections of Elamipretide in Subjects With Primary Mitochondrial Myopathy Followed [malacards.org]

  Çakmak Kearns-Sayre syndrome Schlüsselwörter Kearns Sayre syndrome; ICD 10: H49.8; Chronic progressive external ophthalmoplegia and myopathy, chronic progressive external ophthalmoplegia with ragged red fibers, CPEO with myopathy, CPEO with ragged red [ai-online.info]

• Muscle Weakness

  Other findings in the syndrome may include muscle weakness, short stature, hearing loss, and the loss of ability to coordinate voluntary movements (ataxia) due to problems in the part of the brain called the cerebellum. [rxlist.com]

  Additional symptoms may include mild skeletal muscle weakness, heart block (a cardiac conduction defect), short stature, hearing loss, an inability to coordinate voluntary movements (ataxia), impaired cognitive function, and diabetes. [ninds.nih.gov]

  His manifestations included progressive external ophthalmoplegia, bilateral ptosis, retinitis pigmentosa, and muscle weakness. He was found to harbor an abundant novel deletion in skeletal muscle mitochondrial DNA. [ncbi.nlm.nih.gov]

• Onset at Age <20

  Kearns-Sayre syndrome (KSS) is a neuromuscular disorder defined by the triad of onset before age 20 years, pigmentary retinopathy (a "salt-and-pepper" pigmentation in the retina that can affect vision, but often leaves it intact), and progressive external [rarediseases.info.nih.gov]

  Abstract Kearns-Sayre syndrome (KSS) is a sporadic multisystem mitochondrial disorder characterized by progressive external ophthalmoplegia, pigmentary retinopathy, onset before age 20, and severe cardiac conduction defects that can lead to death. [ncbi.nlm.nih.gov]

  KSS is a slowly progressive mitochondrial disorder with onset before age 20 years. Clinical Presentation: Ataxia, ophthalmoplegia, retinitis pigmentosa, increased cerebrospinal fluid (CSF) protein. [ajnr.org]

  This mitochondrial disorder is characterized by the triad of onset before age 20, chronic progressive external ophthalmoplegia, and pigmentary retinopathy. [n.neurology.org]

• Chronic Progressive External Ophthalmoplegia

  Diplopia can result from asymmetric progression of the chronic external ophthalmoplegia. [eyewiki.aao.org]

  Leigh syndrome chronic progressive external ophthalmoplegia (CPEO): some consider KSS as a syndromic variant of CPEO References Related articles: Inborn errors of metabolism Related articles: Toxic and metabolic encephalopathies Related articles: White [radiopaedia.org]

  Kearns-Sayre syndrome: A neuromuscular disorder characterized by three primary findings: Progressive paralysis of certain eye muscles (chronic progressive external ophthalmoplegia, or CPEO); Abnormal accumulation of colored (pigmented) material on the [rxlist.com]

  Çakmak Kearns-Sayre syndrome Schlüsselwörter Kearns Sayre syndrome; ICD 10: H49.8; Chronic progressive external ophthalmoplegia and myopathy, chronic progressive external ophthalmoplegia with ragged red fibers, CPEO with myopathy, CPEO with ragged red [ai-online.info]

• Cerebellar Ataxia

  The clinical signs of Kearns-Sayre syndrome include chronic progressive external ophthalmoplegia, retinitis pigmentosa, heart block and cerebellar ataxia, as well as other heterogeneous manifestations including neuromuscular problems and endocrine disorders [hkmj.org]

  In addition to the main clinical symptoms, at least one of the following is also often present: heart block, cerebellar ataxia, or cerebrospinal fluid (CSF) protein content above 100 mg/dL. [orpha.net]

  We report a 27-year-old woman with a form of mitochondrial myopathy including chronic progressive external opthalmoplegia, retinal pigmentary dystrophy, cerebellar ataxia, and cardiac conduction block (Kearns-Sayre syndrome). [ncbi.nlm.nih.gov]

• Seizure

  Seizures are infrequent. Several endocrine disorders can be associated with KSS. × Definition Kearns-Sayre syndrome (KSS) is a rare neuromuscular disorder with onset usually before the age of 20 years. [ninds.nih.gov]

  Elevated CSF protein, sensorineural deafness, seizures, and pyramidal signs may also be present. Ragged-red fibers are found on muscle biopsy. [connects.catalyst.harvard.edu]

  “Floppiness,” feeding difficulties and developmental delays are common symptoms; PEO and seizures are less common. [mda.org]

  This progressive disorder is characterized by uncontrolled muscle contractions (myoclonic seizures), dementia, ataxia, and myopathy, which shows ragged-red fibers (indicating mitochondrial proliferation) with specialized stains when biopsied. [merckmanuals.com]

• Cerebellar Sign

  We present a boy of eight years of age with symptoms of Kearns-Sayre syndrome (KSS) characterised by ophthalmoparesis, palpebral ptosis, mitochondrial myopathy, pigmentous retinitis, associated to short stature, cerebellar signs, cardiac blockade, diabetes [ncbi.nlm.nih.gov]

  There were bilateral cerebellar signs. Magnetic resonance imaging (MRI) of the brain showed midbrain and cerebellar atrophy and periaqueductal gliosis [Figure - 1]. MR spectroscopy (MRS) showed lactate peak in the periaqueductal region [Figure - 2]. [annalsofian.org]

  Accompanying the PEO can be cardiac conduction problems (i.e. heart arrythmia), ataxia and cerebellar signs (Vedanarayanan, 2003), deafness (Kokotas et al, 2007), and brainstem disorders. [dizziness-and-balance.com]

  Clinical examination confirmed short stature, global cerebellar signs, muscular weakness, focal, hand and foot dystonia, pigmentous retinitis, ophthalmoparesis with asymmetric palpebral ptosis, and facial diparesis. [scielo.br]

• Facial Muscle Weakness

  PEO6 DNA2 AD PEO w/variable, slowly progressive features; onset: childhood-adulthood Slender build Facial muscle weakness; exertional dyspnea; obstructive sleep apnea; myopathy w/weakness, atrophy, exercise intolerance, myalgia, & cramps; gait disturbance [ncbi.nlm.nih.gov]

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].

• Right Bundle Branch Block

  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 [symptoma.com]

  We are reporting a case of external ophthalmoplegia and retinitis pigmentosa alongwith right bundle branch block. Case report A twenty year old male was seen with the complaint of progresssive drooping of the right upper lid. [ijo.in]

  Laboratory work-up showed subnormal testosterone and growth hormone levels, a subnormal testicular volume, sensorineural deafness, pigmentary retinopathy, complete right bundle branch block and left anterior bundle branch block. [ncbi.nlm.nih.gov]

  On multispecialty consultation, he was found to have right bundle branch block, wasting and weakness of limb muscles, and hearing loss. Sartorius muscle biopsy revealed ragged red fibres on trichrome stain. [mjdrdypu.org]

• Third Degree Atrioventricular Block

  The major anesthetic complication is sudden third-degree atrioventricular block. The patient should therefore be closely monitored at all times and a transcutaneous cardiac pacemaker should be easily available throughout the perioperative period. [accessanesthesiology.mhmedical.com]

  “Aspect of salt and pepper” Figure 4: third degree atrioventricular block on 12-lead electrocardiogram Figure 5: pacemaker implantation on chest X-ray References Kearns TP, Sayre GP. [panafrican-med-journal.com]

  This often progresses to a Third-degree atrioventricular block, which is a complete blockage of the electrical conduction from the atrium to the ventricle. Symptoms of heart block include syncope, exercise intolerance, and bradycardia. [en.wikipedia.org]

• Incomplete Right Bundle Branch Block

  Figure 1 Twelve-lead ECG showing complete atrioventricular block with an incomplete right bundle branch block type of escape rhythm at a rate of 40/min. [casereports.bmj.com]

  EKG showed bradycardia [heart rate of 48 bpm] with a 1st-degree heart block [PR interval of 352 ms] and incomplete right bundle branch block (Figure 1) while echocardiogram showed no abnormalities and preserved left ventricular function. [clinmedjournals.org]

Were CSF folinic acid levels determined at the end of the treatment period? Third, the ineffectiveness of the treatment may be explained by malabsorption of oral folinic acid. [elsevier.es]

Early treatment with high-dose folinic acid therapy seems to be advisable for the treatment of KSS. Eudrac T2007-00-6748-23. [ncbi.nlm.nih.gov]

Early treatment with high-dose folinic acid therapy seems to be advisable for the treatment of KSS. [doi.org]

There is typically no treatment for limitation in eye movement. Endocrinology abnormalities can be treated with drugs. × Treatment There is currently no effective way to treat mitochondria abnormalities in KSS. [ninds.nih.gov]

Prognosis KSS is a slowly progressive disorder. The prognosis for individuals with KSS varies depending on the severity and the number of organs involved. [ninds.nih.gov]

Prognosis The prognosis essentially depends on the number of organs involved and, in each of them, on the proportion of the abnormal mtDNA. In the majority of cases, life expectancy can be normal with appropriate support. [orpha.net]

Applicable To Progressive external ophthalmoplegia with pigmentary retinopathy Use Additional Use Additional Help Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10data.com]

The pathophysiologic etiology of this fluid and its localization to the subfoveal retina remains unclear. [ncbi.nlm.nih.gov]

There have been various hypotheses regarding the etiology of ophthalmoplegia, [2] [3] [4] [5] [6] including possible nuclear ophthalmoplegia and ocular myopathy (KilohNevin). [7] Kearns & Sayre [8] reported this syndrome associated with heart block in [ijo.in]

Objectives: Review the etiology of Kearns-Sayre syndrome. Describe the presentation of Kearns-Sayre syndrome. Summarize the treatment options for Kearns-Sayre syndrome. [statpearls.com]

MeSH terms, Substance MeSH terms Adult Audiometry, Pure-Tone DNA, Mitochondrial/genetics Evoked Potentials, Auditory Female Gene Deletion Hearing Loss, Sensorineural/epidemiology* Hearing Loss, Sensorineural/etiology* Hearing Loss, Sensorineural/physiopathology [ncbi.nlm.nih.gov]

Summary Epidemiology The exact prevalence is unknown, but has been estimated at 1/125,000. [orpha.net]

In epidemiological reports, the condition is considered rare as it has prevalence rate of 1.6 out of 100,000 people of the Finnish population. However, England has a 1.7 prevalence rate out of 100,000. [syndromespedia.com]

We further discuss the renal tubular damage in KSS emphasizing its pathophysiology and clinical phenotype, and review the possible mechanisms of hypoparathyroidism in KSS. [ncbi.nlm.nih.gov]

Pathophysiology In vitro studies of mitochondrial metabolism have identified defects in the respiratory chain and in the oxidative phosphorylation system. [accessanesthesiology.mhmedical.com]

We further discuss the renal tubular damage in KSS emphasizing its pathophysiology and clinical phenotype, and review the possible mechanisms of hypoparathyroidism in KSS. © 2001 S. [karger.com]

To prevent immune reactions, cyclosporine therapy was initiated prophylactically. [ncbi.nlm.nih.gov]

Judicious use of implantable cardioverter defibrillator in this subset population with cardiomyopathy or prolonged QT interval is required in addition to pacing to prevent risk of sudden cardiac death. [clinmedjournals.org]

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.