Case Reports in Neurological Medicine

Case Reports in Neurological Medicine / 2020 / Article

Case Report | Open Access

Volume 2020 |Article ID 7368527 |

Josef Finsterer, Michael Winklehner, Claudia Stöllberger, Thomas Hummel, "Unusual Phenotype and Disease Trajectory in Kearns–Sayre Syndrome", Case Reports in Neurological Medicine, vol. 2020, Article ID 7368527, 6 pages, 2020.

Unusual Phenotype and Disease Trajectory in Kearns–Sayre Syndrome

Academic Editor: Samuel T. Gontkovsky
Received17 Dec 2019
Accepted10 Feb 2020
Published28 Feb 2020


Objective. To describe unusual course and unusual phenotypic features in an adult patient with Kearns–Sayre syndrome (KSS). Case Report. The patient is a 49-year-old male with KSS, diagnosed clinically upon the core features, namely, onset before the age 20 of years, pigmentary retinopathy, and ophthalmoparesis, and the complementary features, namely, elevated CSF protein, cardiac conduction defects, and cerebellar ataxia. The patient presented also with other previously described features, such as diabetes, short stature, white matter lesions, hypoacusis, migraine, hepatopathy, steatosis hepatis, hypocorticism (hyponatremia), and cataract. Unusual features the patient presented with were congenital anisocoria, severe caries, liver cysts, pituitary enlargement, desquamation of hands and feet, bone chondroma, aortic ectasia, dermoidal cyst, and sinusoidal polyposis. The course was untypical since most of the core phenotypic features developed not earlier than in adulthood. Conclusions. KSS is a multisystem disease, but the number of tissues affected is higher than so far anticipated. KSS should be considered even if core features develop not earlier than in adulthood and if unusual features accompany the presentation.

1. Introduction

Kearns–Sayre syndrome (KSS) is a mitochondrial disorder (MID) most frequently due to a single mtDNA deletion and rarely due to mtDNA point mutations [1, 2]. The diagnosis is established clinically if the three core features onset, <20 years of age, chronic progressive external ophthalmoplegia (CPEO), and pigmentary retinopathy, and at least one of the following features are present: cerebrospinal fluid (CSF) protein >100 mg/dl, cardiac conduction defects, or cerebellar dysfunction [1]. Here, we present an adult male with KSS with unusual phenotypic features and disease trajectory.

2. Case Report

The patient is a 49-year-old male, with height 161 cm, weight 85 kg, and a history of preterm birth at gestational week 34 from nonconsanguineous parents, congenital anisocoria, developmental delay, hypoacusis, and tetra-ataxia (Table 1). During childhood general downslowing, chronic fatigue, and sicca syndrome of the eyes occurred. He repeatedly experienced respiratory infections and oral herpetic infections and once painless desquamation of the hands and foot soles (Table 1). He was successfully trained and worked as a hairdresser until the age of 38 years in his parent’s hair saloon and retired at the age of 40 years.

Onset (age)ManifestationTherapy

IntrauterinePremature birth (7 weeks earlier)None
BirthCongenital anisocoriaNone
InfancyDevelopmental delayNone
InfancyHypoacusisHearing devices since age 39
ChildhoodDownslowing, chronic fatigueNone
ChildhoodSicca syndrome + recurrent conjunctivitisEye drops
ChildhoodRecurrent respiratory infectionsAntibiotics
ChildhoodRecurrent herpetic infections, stomatitisVirostatics
5 yPainless desquamation of hands and feetNone
6 yOphthalmoparesis (first recognised)None
7 yTetra-ataxiaNone
18 ySevere cariesFull prosthesis
27 yRight-sided inguinal herniaBassini surgery
29 ySacral dermoidal cystSurgery
30 yBifascicular blockNone
30 yErythema nodosa of feetSteroids
35 yHyper-CKemiaNone
35 yHyperuricemiaDiet
35 yHyponatremia, hypokalemiaNaCl, KCl
36 ySomnolence, infection, suspected BE, SLEAntibiotics, virostatics, endobolin, steroids
36 ySuspected SLENone
36 yElevated CSF proteinNone
36 yDysarthriaNone
36 yPolyposis of nasal sinusesNone
36 yGait disturbance, fallsNone
36 yNeuropsychological deficitsTraining
37 yArterial hypertensionAntihypertensives
37 yHepatopathyNone
37 yLiver cystsNone
37 yRhabdomyolysis (CK: 2673 U/L)None
38 yChondroma/fibroma of the right femurNone
38 ySteatosis hepatisNone
44 ySuspected SLE, Na↓, K↓, migraineAnalgesics
45 yFall, rib fracture, pneumothoraxDrainage
45 yDiabetesAntidiabetics
47 yCataract bilaterallySurgery
49 yAortic ectasiaNone

Left anterior hemiblock plus right bundle branch block, SLE: stroke-like episode, nr: not relevant, CSF: cerebrospinal fluid, BE: Bickerstaff encephalitis.

At age of 30 years, left anterior hemiblock and right bundle-branch-block were recorded. Since age 35, recurrent mild elevation of creatine-kinase (CK) was noted. Aldolase and myoglobin were also elevated. Since age 35, recurrent electrolyte disturbances (hypokalemia and hyponatremia) and hyperuricemia developed. At age 36, he experienced a first episode of disorientation, impaired cognition, bradyphrenia, and secessus urinae. Clinical exam revealed bilateral ophthalmoparesis and dysarthria. Magnetic resonance imaging (MRI) showed subcortical hyperintensities in a nonvascular distribution, which were hyperintens on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) (Figure 1). Neuropsychological testing revealed attention deficits, disability of encoding visual contents, adjustment disorder, and depression. The patient was diagnosed with suspected Bickerstaff encephalitis and questionable seizures. Following these episodes, his gait became disturbed with occasional falls due to increased ataxia. At age 37, he experienced an untriggered rhabdomyolysis. Muscle biopsy from the deltoid muscle suggested muscular dystrophy as only fat but no muscle tissue was detected (Table 2). At age 38, he underwent a second muscle biopsy from the left lateral vastus muscle which showed cytochrome-C-oxidase (COX)-negative fibers (Figure 2(a)), glycogen depositions (Figure 2(b)), fiber splitting, and ragged-red fibers (Figure 2(c)). Electron microscopy showed abnormally shaped and structured mitochondria, megaconia, abnormal glycogen and lipid depositions, and dark bodies (Figures 2(d) and 2(e)). At age 44, migraine developed. At age 47, he underwent cataract surgery bilaterally (Table 1). At age 49, diabetes was diagnosed. Transthoracic echocardiography was normal except for mild enlargement of the ascending aorta (Figure 3).


2000, 30 yearsEchocardiography“Pulmonary insufficiency”
1.1.06Lumbar punctureProtein 167 mg/dl, otherwise normal
3.1.06Lumbar punctureProtein 107 mg/dl, otherwise normal
5.1.06, 35 yearsNerve conduction studiesNormal
4.1.06, 36 yearsCerebral MRIT2-hyperintensities, subcortical, mesencephalon, DWI, ADC hyperintense enlarged pituitary gland, sinusoidal polyposis
12.1.06Neuropsychological testingAttention deficit, disability of encoding visual contents, adjustment disorder, and depression
13.1.06Cerebral MRIUnchanged to previously
17.1.06Lumbar punctureProtein 152 mg/dl, otherwise normal
1/2006Ophthalmologic investigationStrabism, fundus tabulates, AM atrophy, papillary excavation
24.2.06Cerebral MRIBand-like T2-, DWI-, ADC-hyperintensities in the ML and mesencephalon bilaterally
2.1.06Abdominal ultrasoundNormal
1/06Lumbar punctureProtein 167 mg/dl
16.12.06Ophthalmologic investigationPigmentary epithelium shifts, retinal dystrophy, rod/cone degeneration (RP suspected)
8/07Muscle biopsy (deltoid)Fat, no muscle
12.9.07CK2673 U/L (rhabdomyolysis)
10.8.07Myoglobin152 ng/ml (n, 19–92 ng/ml)
2.8.07X-ray of the lungsNormal width of aorta
8.8.07Liver enzymesElevated
9.8.07Abdominal CTMultiple liver cysts
13.8.07Muscle biopsyNo muscle tissue, only fat
13.2.08Muscle MRIChondroma right femur
19.2.08, 38 yearsMuscle biopsy (left lateral vastus)Indicates mitochondrial myopathy
15.12.08Cerebral MRICerebellar atrophy
19.12.08Needle electromyographyIncreased polyphasia exclusively

WMLs: white matter lesions, RP: retinitis pigmentosa.

The family history was positive for hypotonia (mother), diabetes (father, brother of father, grandmother from the father’s side, grand-grandfather from the father’s side), carcinoma (father), and stroke (father). Neurological exam at age 49, revealed short stature, microcephaly, facial dysmorphism, myopathic face, ophthalmoparesis, pupils nonreactive to light, anisocoria (left: 5 mm, right: 3 mm, unrounded), divergence of bulbs, ophthalmoparesis (abduction right bulb 60° abduction left bulb: 15° vertical movements impossible), bilateral ptosis (right > left), reduced corneal reflexes, hypoacusis requiring bilateral hearing devices, dysarthria, dropped head, weakness for right elbow extension and flexion, reduced tendon reflexes on the upper limbs, ataxia and brady-dysdiadochokinesia on the upper limbs, marked wasting of the thighs, ataxia on the lower limbs, truncal ataxia, and ataxic stance, and gait. Gnome calves bilaterally, which were described at age 38 were no longer present. The last medication included indapamide, furosemide/spironolactone, simvastatin, NaCl, KCl, coenzyme-Q (60 mg/d), and vitamin-D.

3. Discussion

The presented patient is interesting in several aspects. Though clinical manifestations of KSS developed already in early infancy and childhood, the majority of the typical phenotypic features (CPEO, pigmentary retinopathy, elevated CSF protein, and cardiac conduction defects) and hepatopathy were recognised not earlier than in adulthood. Possibly, the typical features of KSS required for establishing the diagnosis [1, 2] were present already earlier; however, they were not recognied before age 30. KSS was suspected for the first time at age 39. An argument in favor of the diagnosis of KSS is that the mother was not affected suggesting that there was no transmission of a pathogenic mtDNA variant but rather spontaneous occurrence of a single mtDNA deletion, which is the cause in 96% of cases [3].

Another interesting point is the phenotype. 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. In addition to the features required for diagnosing KSS, the patient presented with the known features of diabetes [4], hypocorticism (hyponatremia) [5], short stature [6], white matter lesions [7], hypoacusis [1], migraine [8], hepatopathy [9], steatosis [10], and cataract [11]. Features so far unreported in KSS include congenital anisocoria, severe caries, liver cysts, pituitary enlargement, desquamation of hands and feet, bone chondroma, aortic ectasia, dermoidal cyst, and polyposis of nasal sinuses. Whether all these features are truly attributable to the underlying metabolic defect remains speculative and requires further investigations, but from other MIDs it is well known that such features can be part of the phenotype [12]. The reason for the high number of novel phenotypic features could be that previous cases were not thoroughly investigated or that the genetic cause of the present patient was different from that of the previous cases.

Concerning the recurrent deteriorations of the phenotype during infections or spontaneously, it cannot be excluded that these conditions were in fact seizures or stroke-like episodes (SLEs), which remained unrecognized and recovered spontaneously. At least 4 of these episodes were documented. An argument for SLEs is that MRI at the first episode at age 36 showed subcortical T2-hyperintensities, which were also hyperintense on DWI and ADC and not confined to a vascular territory, suggesting a vasogenic edema. Whether arterial hypertension should be regarded as a manifestation of the MID is questionable but there are indications from Chinese studies that arterial hypertension can be in fact a phenotypic feature of an MID [4].

Limitations of the study were that the diagnosis was not confirmed by genetic investigations, that the mother was not investigated for the presence of a MID, and that no biochemical investigations of the muscle homogenate were carried out.

In conclusion, this case shows that KSS is indeed a multisystem disease affecting all types of tissues and that the phenotypic presentation may be broader than so far anticipated.

Conflicts of Interest

There are no conflicts of interest.

Authors’ Contributions

Josef Finsterer, Michael Winklehner, Claudia Stöllberger, and Thomas Hummel contributed equally.


  1. J. Finsterer, “Kearns-Sayre syndrome,” Handbook of Mitochondrial Dysfunction, Taylor and Francis Group, Boca Raton, FL, USA, 2019. View at: Google Scholar
  2. L. Welzing, J. C. von Kleist-Retzow, A. Kribs, F. Eifinger, C. Huenseler, and N. Sreeram, “Rapid development of life-threatening complete atrioventricular block in Kearns-Sayre syndrome,” European Journal of Pediatrics, vol. 168, no. 6, pp. 757–759, 2009. View at: Publisher Site | Google Scholar
  3. J. Poulton, J. Finsterer, and P. Yu-Wai-Man, “Genetic counselling for maternally inherited mitochondrial disorders,” Molecular Diagnosis & Therapy, vol. 21, no. 4, pp. 419–429, 2017. View at: Publisher Site | Google Scholar
  4. L. Lin, P. Cui, Z. Qiu et al., “The mitochondrial tRNA(Ala) 5587T>C and tRNA(Leu(CUN)) 12280A>G mutations may be associated with hypertension in a Chinese family,” Experimental and Therapeutic Medicine, vol. 17, pp. 1855–1862, 2019. View at: Publisher Site | Google Scholar
  5. H. J. Southgate and M. D. Penney, “Severe recurrent renal salt wasting in a boy with a mitochondrial oxidative phosphorylation defect,” Annals of Clinical Biochemistry, vol. 37, no. 6, pp. 805–808, 2000. View at: Publisher Site | Google Scholar
  6. A. Berio and A. Piazzi, “Multiple endocrinopathies (growth hormone deficiency, autoimmune hypothyroidism and diabetes mellitus) in Kearns-Sayre syndrome,” La Pediatria Medica e Chirurgica, vol. 35, no. 3, pp. 137–140, 2013. View at: Publisher Site | Google Scholar
  7. M. Sacher, G. M. Fatterpekar, S. Edelstein, C. Sansaricq, and T. P. Naidich, “MRI findings in an atypical case of Kearns-Sayre syndrome: a case report,” Neuroradiology, vol. 47, no. 4, pp. 241–244, 2005. View at: Publisher Site | Google Scholar
  8. M. Magner, H. Kolářová, T. Honzik, I. Švandová, and J. Zeman, “Clinical manifestation of mitochondrial diseases,” Developmental Period Medicine, vol. 19, pp. 441–449, 2015. View at: Google Scholar
  9. C. Ponzetto, N. Bresolin, A. Bordoni et al., “Kearns-Sayre syndrome: different amounts of deleted mitochondrial DNA are present in several autoptic tissues,” Journal of the Neurological Sciences, vol. 96, no. 2-3, pp. 207–210, 1990. View at: Publisher Site | Google Scholar
  10. N. Bresolin, M. Moggio, L. Bet et al., “Progressive cytochromec oxidase deficiency in a case of earns-sayre syndrome: morphological, immunological, and biochemical studies in muscle biopsies and autopsy tissues,” Annals of Neurology, vol. 21, no. 6, pp. 564–572, 1987. View at: Publisher Site | Google Scholar
  11. T. Fritz, K. Wessel, E. Weidle, G. Lenz, and J. Peiffer, “Anästhesie für augenoperationen bei mitochondrialer enzephalomyopathie,” Klinische Monatsblätter für Augenheilkunde, vol. 193, no. 8, pp. 174–178, 1988. View at: Publisher Site | Google Scholar
  12. C. Nesti, A. Rubegni, D. Tolomeo et al., “Complex multisystem phenotype associated with the mitochondrial DNA m.5522G>A mutation,” Neurological Sciences, vol. 40, no. 8, pp. 1705–1708, 2019. View at: Publisher Site | Google Scholar

Copyright © 2020 Josef Finsterer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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