ISSN 0326-646X





Sumario Vol. 42 - Nº 1 Enero - Marzo 2013

Prevention of sudden death in children with Kearns-Sayre syndrome.

Jorge Van Grieken [1], Mauricio Arce [1], Francisco Femenía [1], Martín Arrieta [1], Adrián Baranchuk [3]

1. Unidad de Arritmias. Departamento de Cardiología.
Hospital Español de Mendoza
2. Arrhythmia Service, Kingston General Hospital,
Queen’s University Kingston. Ontario, Canadá.
Av. San Martín 965. Godoy Cruz. Mendoza. Argentina.
CP: 5501 Tel/Fax: 54 261 4490341
Correo electrónico

Recibido 10-OCT-2012 – ACEPTADO después de revisión 06-NOVIEMBRE-2012.

The authors declare not having a conflict of interest.

Print version Imprimir sólo la columna central




Kearns-Sayre syndrome is a rare genetic disorder that involves primarily the mitochondrial DNA, with an altered coding of proteins necessary for the energy chain reaction. It is a mitochondrial cytopathy and the onset of the disease usually occurs early in life and it manifests as a chronic progressive external ophthalmoplegia with retinal degeneration. Cardiac involvement is common, especially conduction disturbances being the most common cause of sudden cardiac death. This dramatic manifestation could be avoided by implanting a permanent pacemaker.

Key words: Kearns-Sayre syndrome; complete AV block; pacemaker.
Rev Fed Arg Cardiol. 2013; 42(1): -



The Kearns-Sayre syndrome (KSS) is a mitochondrial cytopathy caused by a deletion in large scale of mitochondrial DNA (mDNA) and characterized by multiorgan dysfunction with early clinical symptoms before the age of 20 [1]. The diagnostic criteria include progressive chronic external ophthalmoplegia, retinitis pigmentosa associated to one or more of the following alterations: cardiac conduction disorders, cerebellar ataxia or spinal fluid protein concentration >1 g/l. Besides these criteria, other less specific symptoms can be found, such as low height, mental retardation, sensorineural deafness, and endocrine disorders (diabetes mellitus, hypoparathyroidism, growth hormone deficiency) [2,3].

Due to the low frequency of this disease, little is known about its natural history, although it is agreed that conduction disorders and particularly atrio-ventricular block (AVB) of a high degree are frequent causes of sudden cardiac death (SCD), affecting crucially the survival of these patients [4].


Male, 7-year-old patient, product of a pregnancy of twins by artificial insemination, with no family history of genetic diseases. Since his 4 years of age, he presented loss of hearing, muscular weakness, deficit in learning and bilateral palpebral ptosis. (Figure 1A) Before the suspicion of the disease, a genetic analysis was made, showing a great mDNA deletion, compatible with KSS. A pharmacological treatment was indicated based on carnitine, thiamine, Q10 enzyme, and neuromotor stimulation evolving in a stable way. Four months previous to his current admittance, a routine cardiological evaluation was made, with no relevant clinical findings, accompanied by transthoracic echo that showed a mild mitral valve prolapse without clinical repercussion and 24 h Holter recording, where paroxysmal events of AVB, of the 2:1 type appeared, unrelated to symptoms, so the attending physician decided to continue with periodical evaluations. (Figure 1B)

Figure 1 A:  Picture of the patient, where the characteristic palpebral ptosis of the Kearns-Sayre syndrome is observed. B: 24 h Holter recording of three channels, months prior to the admittance. Early P waves are observed (arrow) with polarity similar to conducted P waves compatible with AVB of the 2:1 type with ventriculophasic sinus arrhythmia.


Two days before the current admittance, the child presented tiredness and progressive hypoactivity, and suddenly a syncope episode in rest (sitting down) and without prodromes of approximately 1 min, being moved to the emergency room, where complete AVB was verified, with ventricular escape rhythm between 30 to 35 bpm. (Figure 2A).

Immediately he was referred to the electrophysiology service, where we performed the implant of a permanent single-chamber pacemaker, programmed in VVIR mode (RELIATM RESR01, Medtronic, MN, USA), with spiked bipolar electrodes (CAPSURE® Z NOVUS 5054, Medtronic, MN, USA), under low general sedation and management of airways with anesthesiology care. The procedure was made as usual, as previously described by our group[5], with total duration of the procedure of 35 minutes, a minute of radioscopy and without complications. The patient remained in observation in intermediary therapy in good conditions, being discharged a day later. During the period of follow-up, the child presented a good general state and normal operation of the pacemaker. (Figure 2B)

Figure 2. A: Continuous electrocardiographic recording (leads II and aVF), at the time of admittance of the patient due to syncope episode. Complete AVB is observed, as well as ventricular escape rhythm of less than 40 bpm. B: Continuous electrocardiographic recording (leads I, II, III, aVR, aVL and aVF), carried out 7 days after the discharge of the patient. Pacemaker rhythm at 80 bpm with normal operation of the device.


KSS is due to a large deletion or suppression of mDNA, causing an alteration in the oxidative phosphorylation, which leads to an abnormal production of cell energy [6].

The organs with greater energy requirements, such as the central nervous system and the general muscles, are mainly affected. These mDNA alterations are transmitted by maternal DNA and the genotypic diagnosis is made in most cases by a polymerase chain reaction (PCR) [3], just as it was carried out in this patient once he presented unspecific symptoms of central nervous system and proximal skeletal muscle involvement.

The development of severe cardiac complications predominates in the clinical symptoms of this rare syndrome, and is considered the most significant prognostic factor in the evolution of the disease. Berenberg et al [7] reported that 57% of the patients with KSS presented clinical symptoms of cardiac involvement, including syncope (45%), sudden cardiac death (23%) and cardiomyopathy with heart failure (20%). Likewise, an important association has been established, between KSS and mitral valve prolapse with different degrees of valve insufficiency [7-9].

In relation to cardiac conduction disorders, the electric system is frequently affected, with the involvement being variable, but always progressive. These disorders include prolongation of the intraventricular conduction system, branch blocks and high degree AVB.

It has been posed that patients with KSS and bifascicular block, compared with the general population, present a greater risk of progressing into complete AVB. This aspect becomes more significant because as mentioned above, 23% of these patients die suddenly by complete AVB; so some authors pose permanent pacemaker implantation as prophylaxis and a preventive measure to decrease cardiovascular morbi-mortality [7,10].

We consider and emphasize vigorously the need for a preventive evaluation, as a routine and regularly, of the integrity of the AV conduction system, whether in the patients with a confirmed diagnosis of the disease, and in those with ophthalmoplegia and retinitis even without a certain diagnosis and even in asymptomatic direct relatives, since severe AV conduction disorders typically develop after the appearance of ophthalmologic anomalies [4].

From the electrophysiological point of view, the involvement is mainly at the level of the AV node, His bundle and its branches, displaying HV interval prolongation in rest, which prolongs even more with atrial pacing at increasing rates [11,12].

Advancements in the study of mitochondrial cytopathies have suggested that in the subset of mitochondrial encephalomyopathies, mDNA deletions within cardiomyocytes would be the cause of dilated cardiomyopathy in KSS [13].

Although in the case presented there was no family history of mitochondrial cytopathies, the disease may develop, since there would be the so-called “threshold effect” where the cytopathy manifests clinically by the accumulation of a number enough of mutant mDNA, whether by random segregation during cell division or during the development of the mDNA replication process.

Around 25% of the patients with KSS present mDNA suppression at the site of common deletion and this finding would be related to the involvement of the cardiac electrical conduction system [4].

In the case presented, we think there were sound hints, by the findings in the 24 h Holter recording for the preventive implantation of the permanent pacemaker. A study carried out by Haynes et al [14], with a series of 67 patients with KSS, proved that during a period of 10 years of follow-up, there was a 32% probability that severe disorders of cardiac conduction would develop; 12% of requiring permanent pacemaker implantation; and 5% of probability of SCD. The authors concluded that without permanent ventricular pacing, the risk of SCD is high. This study supports the need to implant a PM as prevention in patients with KSS and different degrees of cardiac electrical involvement.

Besides cardiac pacing, pharmacological treatment is used in an attempt to moderate the progression of the neurological disease. This comprises especially dietary supplements, such as the Q10 coenzyme and ubiquinone. The cardiac response to vitamin supplements is not clear. Some studies report an improvement of the AVB, while others do not report changes in ECG, echo, and cardiac function in the cases of dilated cardiomyopathies [4].

Given the low prevalence of these diseases, the real impact of the dietary therapy on the myocardial involvement is hard to be proved without large population studies. Probably, in a near future, genomic studies may allow us to predict what subset of individuals affected may be in danger of presenting severe alterations of rhythm and help us to make an early preventive intervention [15].


The Kearns-Sayre syndrome is an infrequent clinical entity, but with severe clinical implications associated to cardiac involvement. The evolution of these patients is heterogeneous and the time period in which cardiac involvement appears is unpredictable. There are no concrete elements that would allow us to anticipate this complication, so the timely identification of the subset of patients with cardiac conduction disorders is a priority, given that the permanent pacemaker implantation as prevention, decreases cardiovascular morbi-mortality.



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Publication: March 2013

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