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Kearns-Sayre Syndrome

Kearns Sayre Syndrome

Kearns Sayre syndrome belongs to a group of mitochondrial DNA deletion syndromes, together with pearson syndrome and progressive external ophthalmoplegia (PEO). An onset of progressive ophthalmoplegia and pigmentary retinopathy before the age of 20, accompanied by cardiac and central nervous system abnormalities, are clinical hallmarks of this disorder. The diagnosis rests on clinical criteria, findings from muscle biopsies and biochemical tests, as well as genetic studies.


Presentation

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]
  • Thereafter, he developed short stature, pigmentary retinopathy, progressive external ophthalmoplegia, and ataxia.[ncbi.nlm.nih.gov]
  • 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]
  • An 11-year-old male with bilateral hearing loss, cerebellar dysfunction, short stature, low weight, ptosis, external ophthalmoplegia, and pigmentary retinopathy of both eyes developed chronic subretinal fluid below the central macula.[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[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]
  • An onset of progressive ophthalmoplegia and pigmentary retinopathy before the age of 20, accompanied by cardiac and central nervous system abnormalities, are clinical hallmarks of this disorder.[symptoma.com]
  • 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]
Pediatric Disorder
  • […] unusual presenting features for over 300 pediatric disorders.[euro-libris.ro]
Heart Disease
  • CONTINUE SCROLLING OR CLICK HERE FOR RELATED ARTICLE Last Editorial Review: 1/24/2017 SLIDESHOW Heart Disease: Causes of a Heart Attack See Slideshow[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]
  • Other problems the disease may bring include degeneration of the retina, paralysis of eye muscles and heart disease. “Things can happen quickly,” Kulhanek said. That’s why she’s planning to take Aniah on the trip of a lifetime very soon.[globalgenes.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]
  • Abstract Kearns-Sayre syndrome (KSS) is characterized by external ophthalmoplegia, retinal pigmentation and cardiac conduction defects due to mitochondrial DNA (mtDNA) deletions.[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 mtDNA with large deletions in affected tissues.[radiopaedia.org]
  • It is characterized by a diffuse depigmentation of the retinal pigment epithelium with the greatest effect at the macula.[ojoonline.org]
  • 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]
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]
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]
  • Kearns-Sayre syndrome (KSS) is a rare mitochondrial myopathy and often involves cardiac conduction abnormality and muscle weakness.[ncbi.nlm.nih.gov]
  • The following manifestations are observed: central bilateral sensorineural deafness, pyramidal signs, ataxia, asymmetrical ptosis, external ophthalmoplegia, and progressive muscular weakness secondary to myopathy associated with a significant increase[ncbi.nlm.nih.gov]
  • We found no detectable deletions in the mtDNA of ten non-KSS patients with other mitochondrial myopathies or encephalomyopathies, or three normal controls.[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]
  • 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]
  • The other systemic manifestations included sensorineural hearing loss, slight generalized muscle weakness, cerebellar ataxia, and elevated levels of cerebrospinal fluid protein.[ncbi.nlm.nih.gov]
  • ., diabetes, growth retardation/short stature, and hypoparathyroidism), bilateral sensorineural deafness, dementia, cataracts, and proximal renal tubular acidosis, skeletal muscle weakness (proximal more than distal) and exercise intolerance are additional[ncbi.nlm.nih.gov]
  • Proximal muscle weakness and fatigue appear frequently in KSS patients during follow up. The syndrome in these patients has been caused by mtDNA deletions.[ncbi.nlm.nih.gov]
Waardenburg Syndrome
  • syndrome ワールデンブルグ症候群 PetrusJohannes Waardenburg (1886-1979) Dutch ophthalmologist and geneticist Waldenstrom ワルデンシュトレーム Waldenstrom's macroglobulinemia ワルデンシュトレーム・マクログロブリン血症 Jan GöstaWaldenström (1906 - 1996) Swedishinternist, Waldeyer ワルダイエル Waldeyer's[jams.med.or.jp]
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]
  • Kearns Sayre syndrome Get Update Overview 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[diseaseinfosearch.org]
  • KSS requires onset before age 20 years, although some investigators have reported individuals with CPEO-plus and a disease onset below age 20 years. For Pearson syndrome, the term "Pearson marrow pancreas syndrome" is a synonym.[ncbi.nlm.nih.gov]
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]
  • Onset occurs before age 20, and is manifest as chronic progressive external ophthalmoplegia and retinal degeneration. Management issues of KSS include prophylactic cardiac pacing for conduction defects, which has been shown to improve survival.[ncbi.nlm.nih.gov]
  • The phenotypes of Kearns-Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) are closely associated with deletions of mitochondrial DNA (mtDNA).[ncbi.nlm.nih.gov]
  • 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[ncbi.nlm.nih.gov]
Cerebellar Ataxia
  • We review the differential diagnosis of cerebellar ataxia with vision loss secondary to retinal pigmentary dystrophy.[ncbi.nlm.nih.gov]
  • 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 suggest that a disconnection of Purkinje cells at the dentate nucleus may play a role in the pathogenesis of cerebellar ataxia in KSS.[ncbi.nlm.nih.gov]
  • 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
  • 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]
  • People with KSS might experience endocrine disorders, although seizure activity is infrequent.[disabled-world.com]
  • There is a possibility of seizure problems. About 38% of cases have a short stature build. Hypogonadism is noted to some patients. This is the underdevelopment of the gonads resulting to low testosterone levels in men.[syndromespedia.com]
  • Elevated csf protein, sensorineural deafness, seizures, and pyramidal signs may also be present. Ragged-red fibers are found on muscle biopsy.[icd10data.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]
  • 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]

Workup

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
  • 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]

Treatment

  • 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]
  • Short stature and growth hormone (GH) deficiency have been reported in KSS, but data on GH treatment is limited.[ncbi.nlm.nih.gov]
  • The elevated lactate contents of lesions decreased after one month of CoQ therapy but were re-elevated 10 months after treatment.[ncbi.nlm.nih.gov]

Prognosis

  • 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]
  • 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]
  • Prognosis The condition is considered as progressive that its prognosis is considered as poor. Since the affected are mostly below age twenty, by the time they reach thirty or forty, death may be anticipated.[syndromespedia.com]

Etiology

  • 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]
  • 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]
  • 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]

Epidemiology

  • 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]
Sex distribution
Age distribution

Pathophysiology

  • 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]
  • The pathophysiologic etiology of this fluid and its localization to the subfoveal retina remains unclear.[ncbi.nlm.nih.gov]
  • These 2 cases are presented to describe the possible pathophysiology of mitochondrial diabetes and to emphasize the need to monitor for the development of diabetes in patients with known mitochondrial disease and also to be aware of possible mitochondrial[ncbi.nlm.nih.gov]
  • The pathophysiology of diffusion abnormalities that are associated with degenerative disorders such as mitochondrial diseases remain to be clarified [ 27 ].[doi.org]

Prevention

  • To prevent immune reactions, cyclosporine therapy was initiated prophylactically.[ncbi.nlm.nih.gov]
  • In this case, the necessity of preventive pacemaker implantation in the early stage of cardiac failure was recognized.[ncbi.nlm.nih.gov]
  • Early recognition of adrenal insufficiency is crucial to prevent mortality from this cause.[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]
  • There is no definitive treatment for this condition, but pacemaker implantation can prevent syncope, and reduce morbidity in patients presenting with advanced atrioventricular (AV) conduction abnormalities.[casereports.bmj.com]

References

Article

  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.

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Last updated: 2019-06-28 10:58