|Year : 2014 | Volume
| Issue : 2 | Page : 252-255
Kavita R Bhatnagar1, Divya Gupta2
1 Department of Ophthalmology, Padmashree Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India
2 Department of Ophthalmology, SBKS Medical Institute and Research Center, Vadodara, Gujarat, India
|Date of Web Publication||4-Feb-2014|
Kavita R Bhatnagar
B 4/21, Brahma Aangan, Off Salunke Road, Kondhwa, Pune-411 048
Source of Support: None, Conflict of Interest: None
Kearns-Sayre syndrome (KSS) is a rare neuromuscular disorder. We report a case of a 14-year-old boy diagnosed and treated as myasthenia gravis for (4) years who was eventually diagnosed with KSS. He reported to us 3 years after initial presentation of mild drooping of eyelids with increased severity of ptosis, bilateral external ophthalmoplegia, and atypical retinitis pigmentosa. 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. All these findings confirmed the diagnosis of Kearns-Sayre Syndrome (KSS). The take home message is to have a high index of suspicion for KSS when encountering cases of musculoskeletal disorders in subjects below 20 years of age in view of high morbidity and mortality associated with this syndrome.
Keywords: Pigmentary retinopathy, External ophthalmoplegia, Heart block, myasthenia gravis.
|How to cite this article:|
Bhatnagar KR, Gupta D. Kearns-Sayre syndrome. Med J DY Patil Univ 2014;7:252-5
| Introduction|| |
Kearns-Sayre syndrome (KSS) is a rare neuromuscular disorder characterized by external ophthalmoplegia and pigmentary retinopathy before the age 20 years. Other frequently associated clinical features include cerebellar ataxia, cardiac conduction block, raised cerebrospinal fluid (CSF) protein content, proximal myopathy, short stature, and often have multiple endocrinopathies. Recent reports implicate deletions in mitochondrial DNA (mt DNA). We report a case of a 14 year old boy who was initially misdiagnosed as myasthenia gravis elsewhere as the child had bilateral ptosis and nerve conduction velocity (NCV) with repeated stimulation was also suggestive of myasthenia gravis. Four years later when the patient reported to us, presence of pigmentary retinopathy with bilateral external ophthalmoplegia and bilateral ptosis in a 14 year old boy raised suspicion of KSS. On further investigations, he was found to have right bundle branch block, wasting of limb muscles, hearing loss and ragged red fibers on Sartorius muscle biopsy. These findings lead to the correct diagnosis. The purpose of presenting this case is that KSS during initial presentation may mimick myasthenia gravis. Pigmentary retinopathy and external ophthalmoplegia may present late in the course of the disease.
| Case Report|| |
A 14-year-old boy reported to the eye department of our hospital with a history of bilateral drooping of eyelids for past 4 years with gradually increasing restriction of eye movements in all gazes bilaterally for past 1 year. The other two siblings were normal. Patient had undergone surgery for right-sided undescended testis at the age of 1.2 years. He was diagnosed and treated for myasthenia gravis elsewhere 4 years back. The child's parents discontinued treatment after 6 months on seeing no improvement. On examination, his best corrected visual acuities were 20/20 in both eyes. He had severe bilateral ptosis and extra ocular movements were severely restricted in all directions of gaze [Figure 1] a,b]. Both direct and consensual pupillary reactions were brisk. Fundus examination had similar picture in both eyes. There were areas of widespread RPE (Retinal pigmentary epithelium) alterans and pigmentary retinopathy. CD ratio was 0.3 in OD and 0.4 in OS with healthy neuro-retinal rim [Figure 2]a,b.
General physical examination showed the wasting of limb muscles associated with weakness [Figure 3]. Patient complained of having difficulty in deglutting which was not associated with difficulty in breathing. He also complained of difficulty in hearing.
Multispecialty consultations with cardiology, neurology, audiology, endocrinology, and neuropsychiatry were made. Cardiac evaluation revealed right bundle branch block. His random blood sugar level was borderline raised but endocrinologist ruled out diabetes mellitus. Audiometry showed moderate conductive hearing loss in the left ear (45 dB). A detailed neurologic evaluation was done to rule out any neurologic conditions like myasthenia gravis for which he was once treated. Although nerve conduction velocity (NCV) with repeated stimulation was suggestive of myasthenia gravis but icepack and tensilon tests were negative, antiacetylcholine antibodies were absent and a Computed Tomography (CT) of the thorax was normal. Neurologist ruled out myasthenia in view of the above tests and no response to earlier treatment with tablet Neostigmine as told by child's parents. Serum creatinine level was borderline raised. CSF protein and lactose levels were found to be normal. Muscle biopsy of sartorius muscle was performed. Modified Gomori trichrome staining revealed the presence of ragged red fibers in the muscle specimen. These findings confirmed the diagnosis of Kearns-Sayre Syndrome (KSS) in this patient.
| Discussion|| |
KSS is a rare neuromuscular disorder which belongs to a group of disorders known as mitochondrial encephalomyopathies. The exact etiology of KSS is not clear but studies suggest deletions and/or duplications of mitochondrial DNA (mtDNA) affecting a number of different respiratory enzymes.  Mitochondria are cytoplasm structures responsible for the production of intracellular adenosine triphosphate, which is necessary to supply energy for various metabolic functions. Tissues with high energy demand such as muscle and nervous system are particularly vulnerable to mitochondrial dysfunction. The inheritance of the mitochondrial genome is maternally, because during fertilization, the sperm tail, which contains the mitochondria, is displaced during the penetration of the ovule. 
The classical triad of KSS is onset before 20 years of age, progressive external ophthalmoplegia, and pigmentary retinopathy. This may be associated with heart block, cerebellar syndrome, or CSF protein content of 100 mg/dl or more. The other associations of KSS may be mental retardation, delayed puberty, limb weakness, high-frequency sensorineural hearing loss, seizures, short stature, and cerebral spongiform degeneration.  Endocrine disorders found to be associated with KSS are diabetes mellitus, growth hormone deficiency and hypoparathyroidism. ,
External ophthalmoplegia is one of the uncommon abnormalities found associated with pigmentary degeneration of retina according to Bernard and Scholz who reported four such cases and mentioned that it is not a mere coincidence.  In 1958, Kearns and Sayre were the first to report two cases having the triad of retinitis pigmentosa, external ophthalmoplegia, and complete heart block. ,[ 7] Our patient had all these findings. There have been various hypotheses regarding the etiology of ophthalmoplegia,  including possible nuclear ophthalmoplegia and ocular myopathy (KilohNevin). 
Retinal pathology has been consistently described in all reports of KSS. The retinopathy is usually termed atypical to distinguish it from the more characteristic pigmentary retinopathy of retinitis pigmentosa group of diseases.  The retinal degeneration often occurs centrally and the fundus picture is described as ''salt and pepper'' or ''moth-eaten appearance'.'' Histopathological studies have revealed atrophy of retinal pigmentary epithelium (RPE) and it has been suggested that a breakdown in the energy-dependent interrelationships between the RPE and the photoreceptor layer is responsible for outer retinal degeneration. 
There is currently no effective treatment available for mitochondria abnormalities in KSS and it is generally symptomatic and supportive. A regular and long-term follow-up with cardiologists is most essential and heart blocks may be treated with a pacemaker.
Ophthalmology, audiology, endocrinology, neurology, and neuropsychiatry consultations must also be made.
The ocular course of KSS is relatively benign. The majority of patients has normal or near normal vision. Visual function tests are well preserved which suggests that retinopathy minimally affects photoreceptor function.
Our patient presented with features of myasthenia gravis 4 years back and developed all classical signs (viz. ptosis, bilateral external ophthalmoplegia, atypical retinitis pigmentosa, right bundle branch block, wasting and weakness of limb muscles, hearing loss, and presence of ragged red fibers with trichrome stain in muscle biopsy specimen) of a rare syndrome, that is KSS in due course of time. Take home message: We should have a high index of suspicion for KSS when encountering cases of musculoskeletal disorders below 20 years of age. This is in the interest of the patient in view of high morbidity and mortality associated with KSS. Initial presentation of this syndrome may mimic other musculoskeletal disorders like myasthenia gravis with totally different line of management. Role of ophthalmologist is important because he may be the physician of first contact in majority of these patients.
| References|| |
|1.||Rajakannan, Gayathri, Prasad W, Ramakrishnan R, Prajna NV. Kearns-Sayre syndrome: An atypical presentation. Indian J Ophthalmol 2000;48:54-5. |
|2.||Helico DCJ, Felipe MP, Mario LR, Wolney DAM. Kearns Sayre syndrome: Case Report. Insuf Card 2011; 2: 100-3. |
|3.||Ahmad SS, Ghani SA. Kearns-Sayre syndrome: An unusual ophthalmic presentation. Oman J Ophthalmol. 2012; 5: 115-7. |
|4.||DiMauro S, Schon EA, Rowland LP. Mitochondrial Encephalomyopathies. In: Rowland LP, editor. Merritt's textbook of neurology. 9th ed. Section X: Williams and Wilkins; 2005 p. 615-22. |
|5.||Harvey JN, Barnett D. Endocrine dysfunction in Kearns-Sayre syndrome. Clin Endocrinol (Oxf) 1992;37:97-104. |
|6.||Bernard RI, Scholz RO. Ophthalmolplegia and retinal degeneration. Am J Ophthalmol 1944;27:621. |
|7.||Kearns TP, Sayre GP. Retinitis pigmentosa, external ophthalmoplegia and complete heart block. Arch Ophthalmol 1958;60:280-9. |
|8.||Kearns TP. External Ophthalmoplegia, Pigmentary Degeneration of the Retina, and Cardiomyopathy: A Newly Recognized Syndrome. Trans Am ophthalmol soc. 1965; 63: 559-625. |
|9.||Alfano JE, Berger JP. Retinitis pigmentosa, ophthalmoplegia and spastic quadriplegia. Am J Ophthalmol 1957;43:231-40. |
|10.||Kiloh LG, Nevin S. Progressive dystrophy of the external ocular muscles (Ocular myopathy). Brain 1951;74:115-43. |
|11.||McKechnie NM, King M, Lee WR. Retinal pathology in the Kearns Sayre syndrome. Br J Ophthalmol 1985;69:63-75. |
[Figure 1], [Figure 2], [Figure 3]