A rare case of Kearns–Sayre syndrome in a 17-year-old Venezuelan male with bilateral ptosis as the initial presentation

Abstract

Kearns–Sayre syndrome (KSS) was first described in 1958 as ‘a rare neuromuscular disorder defined by a characteristic triad of progressive external ophthalmoplegia, pigmentary retinopathy, atrioventricular block and cerebellar ataxia’. The prevalence rate of KSS is ∼1–3 per 100 000 individuals. Here, we report a rare case of a 17-year-old Venezuelan male with KSS.

INTRODUCTION

Kearns–Sayre syndrome (KSS) is a rare mitochondrial myopathy characterized by external ophthalmoplegia, pigmentary retinopathy, cerebellar ataxia and heart block. Around 50% of patients develop conductive abnormalities that can ultimately lead to a complete atrioventricular block or bradycardia-related polymorphic ventricular tachycardia. The disease usually presents before 20 years of age with bilateral ptosis, exercise intolerance and nyctalopia [1]. Other frequently associated clinical features include cerebrospinal fluid (CSF) protein elevation or cerebellar ataxia, dementia, acid–base disorders, deafness, proximal myopathy, short stature and several endocrine disorders such as diabetes mellitus, thyroid dysfunctions, Addison's disease and hyperparathyroidism. Only 226 cases have been registered in the literature until 1994. The spontaneous large-scale single deletions of mitochondrial DNA in the germ-cell level during the embryonic development result in KSS [2].

CASE REPORT

A 17-year-old Venezuelan male with a 5-year past medical history of bilateral ptosis came for his regular ophthalmic and general health checkup (Fig. 1). He had diplopia, decreased visual acuity and nyctalopia. He was diagnosed with diplopia by a general practitioner 5 years ago since then the patient has not seen any physician for any eye examination or general health checkup. His personal and family history was non-significant. On examination, he had a short stature one standard below the mean with a BMI within normal limits. Ophthalmologic examination revealed bilateral and partial external ophthalmoplegia with mild limitations in gaze in all directions; visual acuity was four bilaterally with evidence of hypermetric astigmatism. On funduscopic examination, bilateral atypical pigmentary retinopathy was seen (Fig. 2). The differential diagnosis included KSS, chronic progressive external ophthalmoplegia, MELAS syndrome, myasthenia gravis, Pearson syndrome and retinitis pigmentosa. MRI brain, echo, audiometry, urine analysis, serum creatinine kinase, lactate and pyruvate levels, basic metabolic panel, calcium, magnesium, plasma cortisol levels and thyroid profile were normal except for EKG, which unveiled complete right branch block, and a left anterior hemiblock (Fig. 3). The Holter monitor recorded supraventricular extrasystoles and a defect in ventricular repolarization. His CSF protein and lactate levels were elevated. A biopsy of the anterior right tibial muscle showed a higher concentration of mitochondria with notable abnormalities in size, form and disposition of mitochondrial crests (Fig. 4). The diagnosis of KSS was made from the following findings: onset of disease before 20 years of age with chronic external ophthalmoplegia, cardiac conduction defects, pigmentary retinopathy and muscle biopsy.

Figure 1:

Bilateral ptosis.

Figure 2:

(a and b) Funduscopic examination showing atypical pigmentary retinitis.

Figure 3:

Electrocardiogram revealing a complete right bundle branch block and a left anterior hemiblock.

Figure 4:

Electron microscopy of the skeletal muscle tissue revealing abnormal disposition of mitochondrial crests, higher concentration of mitochondria with notable abnormalities in size and shape.

DISCUSSION

Encephalomyopathies are a large group of diseases with an alteration of the oxidative metabolism, resulting in decreased production of energy [3] which include KSS. It was first described in 1958 by Thomas P. Kearns and George P. Sayre as a classic triad of progressive external ophthalmoplegia (PEO), pigmentary retinopathy and cardiac conduction impairment, which usually occurs before age 20 [1]. Our patient has the classic manifestations described above.

KSS occurs as a result of sporadic mitochondrial DNA deletions, ranging from 1000 to 10 000 DNA nucleotides. The most common deletion is 4.9 kb. A smaller proportion of cases are due to mitochondrial DNA duplications that can be transmitted through maternal inheritance [4]. No significant family background was seen in our patient, suggesting that it was most likely sporadic. Bilateral ptosis is the first manifestation of KSS, which is mostly seen in children above 5 years. External ophthalmoplegia usually occurs later after a few years which is mainly affecting peripheral, horizontal and upward [5, 6]; our patient presented the bilateral ptosis at the age of 12 years and was diagnosed with partial external ophthalmoplegia and retinitis pigmentosa at the age of 21. In KSS, few cardiac disorders are found, such as arrhythmias, syncope, cardiomyopathy and conduction system disorders, of which the most common finding is a left anterior hemiblock, isolated or associated with the right bundle branch block [5, 7] in this patient both of the common EKG changes were seen. Other disorders associated with KSS are cerebellar ataxia, nystagmus, dementia, deafness, protein levels, proximal myopathy, exercise intolerance, thyroid disorders, hypoparathyroidism, Addison's disease, dysphagia due to achalasia and renal tubular acidosis [5]. However, our patient did not have any of these. To confirm the diagnosis is necessary to perform a muscle biopsy studied under light microscopy with Gomori staining, in which ragged red fibers are evident. In this case, Gomori stain in light microscopy was not used; however, under electron microscopy alterations in the size and shape of mitochondria, the abnormal arrangement of mitochondrial cristae and paracrystalline inclusions in the matrix were seen which can be considered as a diagnostic criterion [8]. The main complaint of the KSS patients is ophthalmologic manifestations, such as ptosis and external ophthalmoplegia, so it is essential to differentiate it from other entities that have a similar presentation such as myasthenia gravis, PEO and other mitochondrial myopathies. Myasthenia gravis is an autoimmune disease characterized by fluctuating muscle weakness with fatigability. One of the first symptoms is bilateral ptosis, and as the illness advances generalized muscle weakness can compromise respiratory function. In PEO, there is a progressive inability to move the eyes and eyebrows. Both of the diseases differ clinically from KSS by the absence of retinitis pigmentosa and cardiac conduction alterations [5, 8]. The treatment of this syndrome is supportive. Coenzyme Q10 can provide benefit to some patients. It aids in improving the lactate metabolism, heart and muscle function, but does not improve the ocular manifestations [5]. These patients should have an annual ECG, echocardiography, biochemistry and audiometry to screen for common endocrine disturbances are recommended [9]. A permanent pacemaker/implantable cardioverter-defibrillator device is recommended in high-grade heart blocks. It has been shown to improve the prognosis. Cochlear implants should be used in patients with significant sensorineural deafness [10]. Ophthalmologic manifestations may be treated with surgery, but there is a high risk of recurrence and possible ocular complications. KSS is a challenging diagnosis because of the low prevalence and documentation of cases. There should be a clinical suspicion when a patient presents with the classic triad of PEO, pigmentary retinitis and alterations in cardiac conduction. Early diagnosis, palliative treatment and follow-up can prevent possible complications.

CONFLICT OF INTEREST STATEMENT

None declared.

FUNDING

No funding to report.

ETHICAL APPROVAL

The Hospital Universitario de Maracaibo ethical committee gave the permission.

CONSENT

A consent form was obtained from the patient.

GUARANTOR

M.L. and J.L. are guarantors of this study.