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

  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]

• Progressive Ophthalmoplegia

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

  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 [fr-academic.com]

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

  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]

• Plethora

  Though the patient fulfilled the diagnostic criteria for KSS, he additionally presented with a plethora of manifestations, of which some have been reported earlier in KSS. [hindawi.com]

• Hypoxemia

  Arterial blood gas analysis showed no obvious hypoxemia, pH, bicarbonate, and PCO2 were within normal limits. Cardiac assessment presented no obvious ECG changes compared with the previous results. [frontiersin.org]

• Heart Disease

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

  […] the eyes (atypical retinitis pigmentosa), or pigmentary retinopathy, leading to poor night vision and progressive vision loss; and heart disease such as cardiomyopathy and/or progressive arrhythmia leading to complete heart block. [rarediseases.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]

• Myopathy

  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]

  Other mitochondrial myopathies, especially the following: MELAS Syndrome: Progressive neurodegenerative disorder with lactic acidosis, stroke-like episodes. Deafness and diabetes mellitus are frequent. [accessanesthesiology.mhmedical.com]

  "Mitochondrial myopathies". Ann Neuro. 1985; 17: 521–38. 2. Morgan-Hughes JA. The mitochondrial myopathies. In: Engel AG, Banker BQ, ed. Myology: Basic and clinical Vol. 2, New York, McGraw Hill; 1986;1709–43. 3. [annsaudimed.net]

  […] englanti Chronic Progressive External Ophthalmoplegia with Myopathy CPEO with Myopathies CPEO with Myopathy CPEO with Ragged Red Fibers Cpeo With Ragged-Red Fibers Cytopathies, Kearns-Sayre Mitochondrial Cytopathy, Kearn-Sayre Mitochondrial Cytopathy, [finto.fi]

  Yes, these include: Chronic Progressive External Ophthalmoplegia and Myopathy CPEO with Myopathy CPEO with Ragged-Red Fibers KSS Mitochondrial Cytopathy, Kearn-Sayre Type Oculocraniosomatic Syndrome (obsolete) Ophthalmoplegia, Pigmentary Degeneration [mda.org.au]

• Muscle Weakness

  MERRF Syndrome: Mitochondrial encephalopathy characterized by myoclonic epilepsy, muscle weakness, and progressive external ophthalmoplegia. [accessanesthesiology.mhmedical.com]

  weakness and cerebellar ataxia increasing in severity. [elsevier.es]

  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]

  Other clinical features, such as endocrine disorders, dysphagia, ptosis, muscle weakness, fatigue, and hearing loss, can also contribute to the diagnosis. [frontiersin.org]

  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]

• Retinal Pigmentation

  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]

  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]

  Clinical aspects KSS is a multiorgan disease characterized by the clinical triad of a chronic, progressive, external ophthalmoplegia, retinal pigment degeneration (with progressive loss of vision), and onset before the age of 20 years. [accessanesthesiology.mhmedical.com]

• Blepharoptosis

  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]

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

  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]

• 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]

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

  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]

• Chronic Progressive External Ophthalmoplegia

  Yes, these include: Chronic Progressive External Ophthalmoplegia and Myopathy CPEO with Myopathy CPEO with Ragged-Red Fibers KSS Mitochondrial Cytopathy, Kearn-Sayre Type Oculocraniosomatic Syndrome (obsolete) Ophthalmoplegia, Pigmentary Degeneration [mda.org.au]

  Disease name: Kearns-Sayre syndrome ICD 10: H49.8 Synonyms: chronic progressive external ophthalmoplegia and myopathy, chronic progressive external ophthalmoplegia with ragged red fibers, CPEO with myopathy, CPEOwith ragged red fibers, KSSS (Kearns Sayre [orphananesthesia.eu]

  Synonyms Chronic Progressive External Ophthalmoplegia (CPEO) with Myopathy; CPEO with Ragged-Red Fibers; Progressive External Ophthalmoplegia with Ragged-Red Fibers; Kearns Syndrome; Kearns-Sayre Mitochondrial Cytopathy; Kearns-Sayre-Shy-Daroff Syndrome [accessanesthesiology.mhmedical.com]

  external, with ragged red fibers CPEO with ragged red fibers Ophthalmoplegia-Plus Syndrome Chronic Progressive External Ophthalmoplegia With Myopathy edit English Kearns-Sayre syndrome spontaneous occuring or inherited mitochondrial myopathy with a typical [wikidata.org]

  These include: Isolated chronic progressive external ophthalmoplegia (CPEO) Oculopharyngeal muscular dystrophy Myotonic dystrophy Isolated oculopharyngeal myopathy Mendelian chronic progressive external ophthalmoplegia (CPEO) associated with multiple [statpearls.com]

• Cerebellar Ataxia

  ataxia increasing in severity. [elsevier.es]

  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]

  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

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

  Since initiation of the diet, the patient did not have any drop attacks or myoclonic astatic seizures and continued to have the occasional brief nocturnal seizure. Her cognitive function significantly improved. [edm.bioscientifica.com]

  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]

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

• 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]

  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]

  CT-scan carried out at 16 years of evolution revealed signs of generalized cerebral and cerebellar atrophy and areas of hypointensity in basal ganglia (figure 5) and on CT-scan of the chest signs of dilated cardiomyopathy were observed (Figure 6) and [ispub.com]

• 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].

• 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]

Read More Read Less Treatment Treatment There is currently no effective way to treat mitochondria abnormalities in KSS. Treatment is generally symptomatic and supportive. [ninds.nih.gov]

Treatment There is currently no effective way to treat mitochondria abnormalities in KSS. Treatment is generally symptomatic and supportive. Management of KSS involves multiple specialties depending on the organs involved. [brainfacts.org]

Treatment It is important to receive treatment from a medical specialist with a background in treating mitochondrial disorders. [verywellhealth.com]

What is the treatment? There no way of correcting the mitochondrial abnormalities, so treatment is symptomatic and supportive. [gponline.com]

Read More Read Less Prognosis 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]

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

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]

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 Kearns-Sayre syndrome (KSS) exact prevalence is unknown, but has been estimated at 1/125,000. [orpha.net]

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]

Pathophysiology In KSS muscle fibers stains demonstrate ragged red fibers like in other mitochondrial myopathies. [statpearls.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.