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

  Over a period of 10 years, progressive ophthalmoplegia led to recurrent conjunctivitis, keratitis, and corneal ulceration. Almost total external ophthalmoplegia including involvement of the orbicularis oculi muscles was observed. [ncbi.nlm.nih.gov]

  He was determined to have pigmentary retinopathy at age 8 years, which was followed by progressive ophthalmoplegia during the next few years. The patient was significantly shorter in stature than his normal twin and had delayed onset of puberty. [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]

  Kearns-Sayre syndrome (KSS) is a related mitochondrial myopathy that demonstrates the following: chronic progressive ophthalmoplegia (CPEO), onset before the age of 20 and pigmentary degeneration of the retina; abnormal accumulation of colored (pigmented [jmedicalcasereports.biomedcentral.com]

  Report of a family. 61 56 Hurwitz LJ...Chopra JS 5364721 1969 41 External ophthalmoplegia and complete heart block. 61 56 Ross A...Smith J 5762373 1969 42 Progressive ophthalmoplegia. [malacards.org]

• Heart Disease

  CONTINUE SCROLLING OR CLICK HERE FOR RELATED SLIDESHOW SLIDESHOW Heart Disease: Causes of a Heart Attack See Slideshow Last Editorial Review: 1/24/2017 [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]

  Signs & Symptoms The three primary findings in KSS are progressive paralysis of certain eye muscles including the eyelid (ptosis) leading to chronic progressive external ophthalmoplegia (CPEO), pigmentary retinopathy, and heart disease such as an arrhythmia [rarediseases.org]

• Hearing Impairment

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

  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]

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

  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

  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]

  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]

  There is diffuse depigmentation of the retinal pigment epithelium in a salt-and-pepper pattern of pigment clumping and involvement of the peripapillary zone. Study funding No targeted funding reported. [n.neurology.org]

  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

  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]

  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]

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

• Lagophthalmos

  Despite advanced ptosis, there was lagophthalmos of 2 mm with near complete extinction of globe motility in both eyes. The left eye showed a peripheral corneal perforation parallel to the lower limbus. [ncbi.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]

  Kearns-Sayre syndrome is characterized by chronic progressive external ophthalmoplegia, tapetoretinal degeneration and severe generalized myopathy. We report on a 82-year-old male patient with Kearns-Sayre syndrome with open angle glaucoma. [ncbi.nlm.nih.gov]

• Muscle Weakness

  Kearns-Sayre syndrome (KSS) is a rare mitochondrial myopathy and often involves cardiac conduction abnormality and muscle weakness. [ncbi.nlm.nih.gov]

• Osteoporosis

  At age 27, insulin-dependent diabetes mellitus and osteoporosis were diagnosed. Insulin treatment was started and associated endocrinopathies were investigated. [ncbi.nlm.nih.gov]

  Lorenz C Hofbauer, Carolin C Brueck, Shiv K Singh and Harald Dobnig, Osteoporosis in Patients With Diabetes Mellitus, Journal of Bone and Mineral Research, 22, 9, (1317-1328), (2007). [doi.org]

• Chronic Progressive External Ophthalmoplegia

  Progressive External Ophthalmoplegia With Myopathy Statements Identifiers Sitelinks Wikipedia (10 entries) edit Wikibooks (0 entries) edit Wikiquote (0 entries) edit Wikisource (0 entries) edit Wikiversity (0 entries) edit Wikivoyage (0 entries) edit [wikidata.org]

  Kearns-Sayre syndrome is characterized by chronic progressive external ophthalmoplegia, tapetoretinal degeneration and severe generalized myopathy. We report on a 82-year-old male patient with Kearns-Sayre syndrome with open angle glaucoma. [ncbi.nlm.nih.gov]

• Cerebellar Ataxia

  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]

  53 ページ - Neurological abnormalities are prominent, including severe hypotonia, areflexia, poor suck rellex and seizures. Neuronal migration defects may be observed on neuroimaging. [books.google.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 Diabetes Seizures (infrequent) Several [blouw.moneomed.com]

  Seizures are infrequent. Several endocrine disorders can be associated with KSS. Treatment There is currently no effective way to treat mitochondria abnormalities in KSS. Treatment is generally symptomatic and supportive. [childneurologyfoundation.org]

  […] findings may include increased levels of protein in the cerebrospinal fluid, dementia, encephalopathy, cerebellar ataxia, bulbar weakness (dysphagia, which may also be related to cricopharyngeal achalasia), electroencephalographic anomalies (including seizures [accessanesthesiology.mhmedical.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]

  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]

  signs, impaired cognitive dysfunction, diabetes mellitus 2, and other endocrine disorders. [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]

• 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]

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 ... [accessanesthesiology.mhmedical.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]

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

Management and treatment Treatment of KSS is supportive. Regular follow-up with a cardiologist is recommended. [orpha.net]

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. [ninds.nih.gov]

Moreover, it is conceivable that a combination of various degrees of swallowing difficulties with different patterns in manometric studies exist, each playing a major role in the prognosis, natural history, and quality of life of KSS patients. [ncbi.nlm.nih.gov]

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

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]

Etiology KSS is caused by deletions of large portions of mitochondrial DNA (mtDNA), resulting in the loss of genes involved in the oxidative phosphorylation pathway. [orpha.net]

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]

Desnuelle Revue Neurologique (2010) Different pathophysiological mechanisms of intramitochondrial iron accumulation in acquired and congenital sideroblastic anemia caused by mitochondrial DNA deletion Thomas Matthes, Pierre Rustin, Hedwige Trachsel, Regis [nature.com]

The pathophysiology of diffusion abnormalities that are associated with degenerative disorders such as mitochondrial diseases remain to be clarified [ 27 ]. [doi.org]

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

Kearns-Sayre Syndrome is a serious medical disorder caused by genetic and non-genetic factors in an individual; it cannot be prevented Avoid medications that adversely affect mitochondria, or its function; and the use of dental anesthetic, such as articaine [dovemed.com]

The goals of this research are to increase understanding of these disorders, and to find ways to prevent, treat, and, ultimately, cure them. [childneurologyfoundation.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.