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Jervell and Lange-Nielsen syndrome in cochlear implanted patients: Our experience and a review of literature
International Journal of Pediatric Otorhinolaryngology 79 (2015) 1544–1547
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Jervell and Lange-Nielsen syndrome in cochlear implanted patients: Our experience and a review of literature Ali Eftekharian *, Mozhgan Hosseinerezai Mahani Hearing Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
A R T I C L E I N F O
A B S T R A C T
Article history: Received 20 May 2015 Received in revised form 3 July 2015 Accepted 4 July 2015 Available online 14 July 2015
Objectives: To share our experience in cochlear implanted patients with Jervell and Lange-Nielsen syndrome (JLNS), to review the literature results and to disclose precautions which have to be taken dealing with these patients. Materials and methods: Electrocardiograms (ECG) of 503 children with congenital bilateral profound hearing loss which were cochlear implanted in cochlear implant center of a tertiary hospital were evaluated for long QT syndrome. Clinical reports of the patients with JLNS were evaluated and a review of literature performed. Results: The prevalence of disease was 0.79% (four cases) in our center which is in the range of literature reports (0–2.6%). None of our patients had a history of syncopal attack. Two patients (50%) were born from parents with consanguineous marriage. Considering all precautions their cochlear implant surgeries were done uneventfully. A review of the literature has identified sixteen reports on cochlear implantation in a total of 38 children with JLNS. Similar to our cases none of the authors reported cardiac events during device switch-on. Nine available reports about the outcome of cochlear implantation in these patients indicated good auditory outcome. Conclusion: It is recommended that all congenitally deaf patients have an ECG taken as a part of the evaluation. As auditory stimuli is reported to be a specific trigger, it is prudent to activate the processor with continuous heart monitoring even though there is no reported cardiac event during device switchon. Cochlear implantation can be performed relatively safely in these patients if necessary precautions have been taken appropriately and their auditory outcome is good. Triggers of the cardiac events should be avoided throughout their life. ß 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Jervell and Lange-Nielsen syndrome Long QT syndrome Cochlear implantation Congenital hearing loss
1. Introduction Congenital long QT syndrome (LQTS) is a hereditary cardiac disease characterized by a prolongation of the QT interval at basal electrocardiogram (ECG) and by a high risk of life-threatening arrhythmias [1]. Four clinical types of LQTS have been defined [2]. Although all these four types are rare, two more prevalent variants of LQTS are: Jervell and Lange-Nielsen syndrome (JLNS), which is an autosomal recessive form of LQTS associated with congenital deafness and a high incidence of sudden cardiac death in childhood, and RomanoWard syndrome, which is an autosomal dominant form of LQTS
* Corresponding author at: Hearing Disorders Research Center, Loghman Hospital, Kamali Ave. Kargar, 13336-31151 Tehran, Iran. Tel.: +98 21 55405315; fax: +98 21 55416170. E-mail address: [email protected] (A. Eftekharian). http://dx.doi.org/10.1016/j.ijporl.2015.07.012 0165-5876/ß 2015 Elsevier Ireland Ltd. All rights reserved.
that like the other two types of this syndrome is not associated with deafness [2–4]. Mutations in two genes, the KCNQ1 and KCNE1 gene, are known to be causing JLNS. These two genes encode for proteins that take part in the regulation of the potassium flow in the heart and the inner ear [5]. Reported prevalence of JLNS among children with congenital deafness is different in various populations and was found to be between 0 and 2.6% [5–9]. JLNS can occur among deaf children without obvious signs of the disease [5]. But almost 90% of the patients become symptomatic and that sudden death exceeds 25% despite medical therapy. During the first year of life 15% already had an event, by age 3 years 50% have had an event, and by age 18 years a staggering 90% had symptoms [10]. Most JLNS patients experience cardiac events associated with exercise or emotion. Swimming, auditory stimuli, anesthesia, and fever have also been reported as specific triggers in these patients. Many of the JLNS patients have been
A. Eftekharian, M.H. Mahani / International Journal of Pediatric Otorhinolaryngology 79 (2015) 1544–1547
misdiagnosed with epilepsy and treated with antiepileptic drugs before the JLNS diagnosis has been established [5]. Otolaryngologists, audiologist and anyone who works on these patients (especially cochlear implantation teams) must be aware of the hazards and precautions that should be taken when dealing with this disease not only in surgical situations but also during the whole life of their patients. The aim of this study is to share our experience, to compare it with the literature results and to disclose precautions which have to be taken dealing with these patients.
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Table 1 Demographic characteristics of cases. Case
Sex
Age at surgery (months)
Side of surgery
Anomaly of temporal bone
Parents with consanguineous marriage
Implant type
1 2 3 4
Male Female Female Female
22 52 41 209
Right Left Left Right
No No No No
No No Yes Yes
CI24RE HiRes90k1j HiRes90k1j CI24RE
2. Materials and methods Electrocardiograms of 503 Children with congenital bilateral profound hearing loss which were cochlear implanted in cochlear implant center of a tertiary hospital in Iran were evaluated for long QT syndrome. Corrected QT interval (QTc) greater than 480 milliseconds was considered as long QT. Clinical reports of the patients with congenital long QT syndrome were evaluated. A review of the literature in PubMed, Scopus and Google was also performed to identify published English language journal articles of cases of cochlear implanted patients with Jervell and LangeNielsen syndrome.
None of our patients had either a history of syncopal attack or family history of JLNS. Two patients (50%) were born from parents with consanguineous marriage. One of these patients (case number 3) had a history of a sister with sudden death which might be due to an unrecognized long QT syndrome. Computerized tomography scanning of all four children showed normal anatomy of the inner ear and also we had not found any anomaly during their surgery. All precautions were considered during surgery and their operations were done without any difficulties or complications. Fortunately until present none of these patients reported any cardiac events and they continue to use their implants successfully.
3. Results 4. Discussion Among 503 Children with congenital profound hearing loss that were cochlear implanted in our center four children had prolonged QTc. Thus, prevalence of congenital long QT syndrome is 0.79% in our studied population. Demographic characteristics of these patients are shown in Table 1. ECG of one of these children is shown in Fig. 1. All these children were referred for genetic evaluation but, unfortunately due to its costs only one child took the exam (case number one). This child did not have mutation in KCNQ1 gene.
Prevalence of JLNS among children with congenital deafness is different in various populations and was found to be between 0 and 2.6% [5–9]. Ocal et al. [9] pointed that in 10 studies which screened 6557 deaf children, the prevalence was found to average 0.21%, with a range of 0–0.43%. Although consanguineous marriage is more prevalent in our population it seems that prevalence of the disease is still within this range. One of our cases (case number 3)
Fig. 1. Electrocardiogram of one of the cases shows QTc prolongation (531 ms).
1546
A. Eftekharian, M.H. Mahani / International Journal of Pediatric Otorhinolaryngology 79 (2015) 1544–1547
had a sibling with history of sudden death. It is prudent that all siblings of patients with LQTS be carefully evaluated for this disease. None of our cases reported cardiac events. As Siem et al. [5] have also stated, JLNS can occur among deaf children without obvious signs of the disease. Thus, a negative family history and no clinical findings do not exclude the diagnosis of congenital long QT syndrome. According to Kang et al. [7] although this disease is rare, the ECG is a simple, inexpensive and non-invasive investigation which can be the first indicator of serious underlying pathology. While it had been known that most patients would develop their symptoms under stress, it was also known that in a minority of cases these life-threatening cardiac events could occur at rest [1]. Triggers for intense or sudden emotion; activities that are known to precipitate syncopal events in individuals with long QT syndrome, includes: competitive sports, amusement park rides, frightening movies and jumping into cold water [11]. Auditory stimuli such as an alarm clock or a telephone bell, anesthesia, and fever have also been reported as specific triggers [1,5,12]. Drugs that cause further prolongation of the QT interval should be avoided. Some of these are frequently used by children. Among them antibiotics and drugs used against asthma (i.e., erythromycin, terbutaline), should be avoided by these patients [5]. Because JLNS patients are exposed to ventricular arrhythmias, patients should be equipped with paddles for defibrillation during surgery [5]. Careful attentions should be given at the induction of anesthesia and during wake up, when the patient is presumably experiencing most stress [5]. As arrhythmias are triggered by conditions associated with increased sympathetic activity, medication containing sympathomimetic (i.e., epinephrine) should be avoided [5]. Drugs such as Halothane, which sensitize the myocardium to the effect of catecholamine, should also be avoided. Beta-blocker therapy is the first choice for LQTS. It dramatically decreases event rates, from 0.97 to 0.31 events per patient per year [12]. Cardiac events in LQTS patients are generally well controlled with b-blocker therapy. However, patients with a history of aborted cardiac arrest, symptomatic patients in the first year of life, and patients with JLNS carrying KCNQ1 mutations are at particularly high risk and therefore, special aids, including implantable cardioverter defibrillator and left cardiac sympathetic denervation on top of b-blocker therapy may be deemed necessary because of the high recurrence rate of fatal arrhythmia [12]. Besides medical treatment, life-style advice for patients is important [12] and previously described triggers (e.g. jumping into cold water) should be avoided as much as possible. A review of the literature has identified sixteen reports on cochlear implantation in a total of 38 children with JLNS (Table 2) [5–7,13–25]. None of these authors have reported cardiac events during device switch-on. Also, we did not experience such an event during device switch-on in our cases. But, as auditory stimuli is reported to be as specific trigger [1,5,12], we agree with Siem et al. [5] who recommended that the activation of the processor is done during continuous heart monitoring with a defibrillator at hand, preferably at the pediatric intensive care unit. According to Crotti et al. [1] even though the clinical diagnosis of JLNS is rather straightforward, it is important to genotype all these patients because it has been shown that the smaller group with KCNE1 mutations has a markedly less severe clinical course than that with mutations on KCNQ1 which could influence therapeutic management. All of our cases were referred for genetic evaluation but, unfortunately due to its costs only one child took the exam. A review of the literature on sixteen reports of cochlear implantation in a total of 38 children with JLNS
Table 2 Review of literature (implanted cases). Authors
Number of cases
Cardiac events during device switch-on
Gene evaluation
Outcomes of cochlear implant
Baines et al. (1999) Green et al. (2000) Chorbachi et al. (2002) Neamt¸u et al. (2003) Rajput et al. (2003) Berrettini et al. (2003) Daneshi et al. (2007) Siem et al. (2008) Yanmei et al. (2008) Kang et al. (2011) Raghunandhan et al. (2011) Senthil Vadivu et al. (2013) Broomfield et al. (2013)
1 1 2
No data No No
No No Yes
No data Good Good
1 2 1
No No data No
No No data No
Good No data Good
3
No
No
Good
8 1
No No
Yes No
Good Good
1 1
No No data
No No data
No data No data
4
No
No
Good
5
No
No
5
No data
Yes
Two of them died, the rest were good No data
1 1
No data No data
No No
No data No data
Winbo and Rydberg (2015) Kumar et al. (2015) Yadav and Sikka (2015)
[5–7,13–25] revealed that only in three of them gene evaluation were done for their patients (Table 2). For older reports this may be due to unavailability of these tests but for the recent reports, this could be due to its costs especially in developing countries like ours. Nine available reports about the outcome of cochlear implantation in these patients (Table 2) indicated good auditory outcome. All our patients have also shown good performance with their devices. So, as Yanmei and his colleagues [6] have stated, the auditory and language outcome after cochlear implantation in this syndrome at least is not worse than those in patients with nonsyndromic sensorineural deafness. 5. Conclusions Although JLNS is a rare disease, due to its life treatening feature, all congenitally deaf patients should have an ECG taken as a part of their evaluation. As auditory stimuli is reported to be a specific trigger it is prudent that to activate the processor with continuous heart monitoring even though there is no reported cardiac event during device switch-on. Our data as well as the litreature review confirms that cochlear implantation can be performed relatively safely in patients with Jervell and Lange-Nielsen syndrom if necessary precautions have been taken appropriately and their auditory outcome is good. Triggers of the cardiac events should be avoided throughout the life of these patients. Financial disclosure The authors did not have any financial or material support for this work. Conflicts of interest The authors declare that they have no conflict of interest.
A. Eftekharian, M.H. Mahani / International Journal of Pediatric Otorhinolaryngology 79 (2015) 1544–1547
References [1] L. Crotti, G. Celano, F. Dagradi, P.J. Schwartz, Congenital long QT syndrome, Orphanet J. Rare Dis. 7 (2008) 18. [2] P.L. Hedley, P. Jørgensen, S. Schlamowitz, R. Wangari, J. Moolman-Smook, P.A. Brink, J.K. Kanters, V.A. Corfield, M. Christiansen, The genetic basis of long QT and short QT syndromes: a mutation update, Hum. Mutat. 30 (2009) 1486–1511. [3] A. Jervell, F. Lange-Nielsen, Congenital deaf-mutism, functional heart disease with prolongation of the QT interval, and sudden death, Am. Heart J. 54 (1957) 59–68. [4] O.C. Ward, A new familial cardiac syndrome in children, J. Ir. Med. Assoc. 54 (1964) 103–106. [5] G. Siem, A. Fru¨h, T.P. Leren, K. Heimdal, E. Teig, S. Harris, Jervell and Lange-Nielsen syndrome in Norwegian children: aspects around cochlear implantation hearing, and balance, Ear Hear. 29 (2008) 261–269. [6] F. Yanmei, W. Yaqin, S. Haibo, Z. Huiqun, C. Zhengnong, Y. Dongzhen, Y. Shankai, Cochlear implantation in patients with Jervell and Lange-Nielsen syndrome, and a review of literature, Int. J. Pediatr. Otorhinolaryngol. 72 (2008) 1723–1729. [7] S.L.S. Kang, C. Jackson, W. Kelsall, Electrocardiogram screening of deaf children for long QT syndrome: are we following UK national guidelines? J. Laryngol. Otol. 125 (2011) 354–356. [8] S. Sopontammarak, A. Khongphatthanayothin, P. Sa-Nguanchua., Prevalence of idiopathic long QT syndrome in congenital sensori-neural hearing loss students of Songkhla School for the Deaf, J. Med. Assoc. Thail. 86 (2003) 1149–1155. [9] B. Ocal, A. Imamoglu, S. Atalay, H. Ercan Tutar, Prevalence of idiopathic long QT syndrome in children with congenital deafness, Pediatr. Cardiol. 18 (1997) 401–405. [10] P.J. Schwartz, C. Spazzolini, L. Crotti, J. Bathen, J.P. Amlie, K. Timothy, M. Shkolnikova, C.I. Berul, M. Bitner-Glindzicz, L. Toivonen, M. Horie, E. Schulze-Bahr, I. Denjoy, The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome, Circulation 113 (2006) 783–790. [11] L. Tranebjærg, R.A. Samson, G.E. Green, Jervell and Lange-Nielsen Syndrome, in: R.A. Pagon, M.P. Adam, H.H. Ardinger, S.E. Wallace, A. Amemiya, L.J.H. Bean, T.D. Bird, C.R. Dolan, C.T. Fong, R.J.H. Smith, K. Stephens (Eds.), GeneReviews1 [Internet]. Seattle (WA), University of Washington, Seattle, 2002 Jul 29, , 1993–2015 (updated 2014 Nov 20).
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[12] Y. Mizusawa, M. Horie, A.A. Wilde, Genetic and clinical advances in congenital long QT syndrome, Circ. J. 78 (2014) 2827–2833. [13] D.B. Baines, D.D. Murrell, Preoperative hypoglycaemia, propranolol and the Jervell and Lange-Nielsen syndrome, Paediatr. Anaesth. 9 (1999) 156–158. [14] J.D. Green, M.J. Schuh, B.R. Maddern, J. Haymond, R.A. Helffrich, Cochlear implantation in Jervell and Lange-Nielsen syndrome, Ann. Otol. Rhinol. Laryngol. Suppl. 185 (2000) 27–28. [15] R. Chorbachi, J.M. Graham, J. Ford, C.H. Raine, Cochlear implantation in Jervell and Lange-Nielsen syndrome, Int. J. Pediatr. Otorhinolaryngol. 66 (2002) 213–221. [16] D. Neamþu, S. Cotulbea, A.H. Marin, S. Lupescu, H. Stefanescu, V. Draganescu, D. Trales, N. Balica, A. Ruja, A. Mag, Cochlear implant in Jervell and Lange-Nielsen syndrome, J. Exp. Med. Surg. Res. 4 (2010) 275–276. [17] K. Rajput, T. Brown, D.E. Bamiou, Aetiology of hearing loss and other related factors versus language outcome after cochlear implantation in children, Int. J. Pediatr. Otorhinolaryngol. 67 (2003) 497–504. [18] S. Berrettini, F. Forli, F. Ursino, S.S. Franceschini, Cochlear implant in Jervell and Lange-Nielsen syndrome, Audiol. Med. 1 (2003) 224–227. [19] A. Daneshi, M.M. Ghassemi, M. Talee, S. Hassanzadeh, Cochlear implantation in children with Jervell Lange-Nielsen syndrome, J. Laryngol. Otol. 122 (2008) 314–317. [20] S. Raghunandhan, M. Kameswaran, R.S. Anand Kumar, A.K. Agarwal, M.D. Hossain, A study of complications and morbidity profile in cochlear implantation: the MERF experience, Indian J. Otolaryngol. Head Neck Surg. 66 (2014) 161–168. [21] A. Senthil Vadivu, R. Sampath, V.K. Paramasivan, M. Mohan, M. Kameswaran, Cochlear implantation and cardiac associations, Int. J. Pediatr. Otorhinolaryngol. 77 (2013) 1303–1307. [22] S.J. Broomfield, I.A. Bruce, L. Henderson, R.T. Ramsden, K.M. Green, Cochlear implantation in children with syndromic deafness, Int. J. Pediatr. Otorhinolaryngol. 77 (2013) 1312–1316. [23] A. Winbo, A. Rydberg, Vestibular dysfunction is a clinical feature of the Jervell and Lange-Nielsen Syndrome, Scand. Cardiovasc. J. 49 (2015) 7–13. [24] M. Kumar, D.K. Baidya, V.K. Mohan, Mamta, Safe anesthesia management protocol of a child with congenital long QT syndrome and deafness (Jervell and LangeNielsen syndrome) for cochlear implant surgery, Saudi J. Anaesth. 9 (2015) 98–99. [25] V. Yadav, K. Sikka, Cardiac precautions in patient with Jervell and Lange-Nielson syndrome undergoing cochlear implantation, Indian J. Otol. 21 (2015) 78–79.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Jervell and Lange-Nielsen syndrome in cochlear implanted patients: Our experience and a review of literature Ali Eftekharian *, Mozhgan Hosseinerezai Mahani Hearing Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
A R T I C L E I N F O
A B S T R A C T
Article history: Received 20 May 2015 Received in revised form 3 July 2015 Accepted 4 July 2015 Available online 14 July 2015
Objectives: To share our experience in cochlear implanted patients with Jervell and Lange-Nielsen syndrome (JLNS), to review the literature results and to disclose precautions which have to be taken dealing with these patients. Materials and methods: Electrocardiograms (ECG) of 503 children with congenital bilateral profound hearing loss which were cochlear implanted in cochlear implant center of a tertiary hospital were evaluated for long QT syndrome. Clinical reports of the patients with JLNS were evaluated and a review of literature performed. Results: The prevalence of disease was 0.79% (four cases) in our center which is in the range of literature reports (0–2.6%). None of our patients had a history of syncopal attack. Two patients (50%) were born from parents with consanguineous marriage. Considering all precautions their cochlear implant surgeries were done uneventfully. A review of the literature has identified sixteen reports on cochlear implantation in a total of 38 children with JLNS. Similar to our cases none of the authors reported cardiac events during device switch-on. Nine available reports about the outcome of cochlear implantation in these patients indicated good auditory outcome. Conclusion: It is recommended that all congenitally deaf patients have an ECG taken as a part of the evaluation. As auditory stimuli is reported to be a specific trigger, it is prudent to activate the processor with continuous heart monitoring even though there is no reported cardiac event during device switchon. Cochlear implantation can be performed relatively safely in these patients if necessary precautions have been taken appropriately and their auditory outcome is good. Triggers of the cardiac events should be avoided throughout their life. ß 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Jervell and Lange-Nielsen syndrome Long QT syndrome Cochlear implantation Congenital hearing loss
1. Introduction Congenital long QT syndrome (LQTS) is a hereditary cardiac disease characterized by a prolongation of the QT interval at basal electrocardiogram (ECG) and by a high risk of life-threatening arrhythmias [1]. Four clinical types of LQTS have been defined [2]. Although all these four types are rare, two more prevalent variants of LQTS are: Jervell and Lange-Nielsen syndrome (JLNS), which is an autosomal recessive form of LQTS associated with congenital deafness and a high incidence of sudden cardiac death in childhood, and RomanoWard syndrome, which is an autosomal dominant form of LQTS
* Corresponding author at: Hearing Disorders Research Center, Loghman Hospital, Kamali Ave. Kargar, 13336-31151 Tehran, Iran. Tel.: +98 21 55405315; fax: +98 21 55416170. E-mail address: [email protected] (A. Eftekharian). http://dx.doi.org/10.1016/j.ijporl.2015.07.012 0165-5876/ß 2015 Elsevier Ireland Ltd. All rights reserved.
that like the other two types of this syndrome is not associated with deafness [2–4]. Mutations in two genes, the KCNQ1 and KCNE1 gene, are known to be causing JLNS. These two genes encode for proteins that take part in the regulation of the potassium flow in the heart and the inner ear [5]. Reported prevalence of JLNS among children with congenital deafness is different in various populations and was found to be between 0 and 2.6% [5–9]. JLNS can occur among deaf children without obvious signs of the disease [5]. But almost 90% of the patients become symptomatic and that sudden death exceeds 25% despite medical therapy. During the first year of life 15% already had an event, by age 3 years 50% have had an event, and by age 18 years a staggering 90% had symptoms [10]. Most JLNS patients experience cardiac events associated with exercise or emotion. Swimming, auditory stimuli, anesthesia, and fever have also been reported as specific triggers in these patients. Many of the JLNS patients have been
A. Eftekharian, M.H. Mahani / International Journal of Pediatric Otorhinolaryngology 79 (2015) 1544–1547
misdiagnosed with epilepsy and treated with antiepileptic drugs before the JLNS diagnosis has been established [5]. Otolaryngologists, audiologist and anyone who works on these patients (especially cochlear implantation teams) must be aware of the hazards and precautions that should be taken when dealing with this disease not only in surgical situations but also during the whole life of their patients. The aim of this study is to share our experience, to compare it with the literature results and to disclose precautions which have to be taken dealing with these patients.
1545
Table 1 Demographic characteristics of cases. Case
Sex
Age at surgery (months)
Side of surgery
Anomaly of temporal bone
Parents with consanguineous marriage
Implant type
1 2 3 4
Male Female Female Female
22 52 41 209
Right Left Left Right
No No No No
No No Yes Yes
CI24RE HiRes90k1j HiRes90k1j CI24RE
2. Materials and methods Electrocardiograms of 503 Children with congenital bilateral profound hearing loss which were cochlear implanted in cochlear implant center of a tertiary hospital in Iran were evaluated for long QT syndrome. Corrected QT interval (QTc) greater than 480 milliseconds was considered as long QT. Clinical reports of the patients with congenital long QT syndrome were evaluated. A review of the literature in PubMed, Scopus and Google was also performed to identify published English language journal articles of cases of cochlear implanted patients with Jervell and LangeNielsen syndrome.
None of our patients had either a history of syncopal attack or family history of JLNS. Two patients (50%) were born from parents with consanguineous marriage. One of these patients (case number 3) had a history of a sister with sudden death which might be due to an unrecognized long QT syndrome. Computerized tomography scanning of all four children showed normal anatomy of the inner ear and also we had not found any anomaly during their surgery. All precautions were considered during surgery and their operations were done without any difficulties or complications. Fortunately until present none of these patients reported any cardiac events and they continue to use their implants successfully.
3. Results 4. Discussion Among 503 Children with congenital profound hearing loss that were cochlear implanted in our center four children had prolonged QTc. Thus, prevalence of congenital long QT syndrome is 0.79% in our studied population. Demographic characteristics of these patients are shown in Table 1. ECG of one of these children is shown in Fig. 1. All these children were referred for genetic evaluation but, unfortunately due to its costs only one child took the exam (case number one). This child did not have mutation in KCNQ1 gene.
Prevalence of JLNS among children with congenital deafness is different in various populations and was found to be between 0 and 2.6% [5–9]. Ocal et al. [9] pointed that in 10 studies which screened 6557 deaf children, the prevalence was found to average 0.21%, with a range of 0–0.43%. Although consanguineous marriage is more prevalent in our population it seems that prevalence of the disease is still within this range. One of our cases (case number 3)
Fig. 1. Electrocardiogram of one of the cases shows QTc prolongation (531 ms).
1546
A. Eftekharian, M.H. Mahani / International Journal of Pediatric Otorhinolaryngology 79 (2015) 1544–1547
had a sibling with history of sudden death. It is prudent that all siblings of patients with LQTS be carefully evaluated for this disease. None of our cases reported cardiac events. As Siem et al. [5] have also stated, JLNS can occur among deaf children without obvious signs of the disease. Thus, a negative family history and no clinical findings do not exclude the diagnosis of congenital long QT syndrome. According to Kang et al. [7] although this disease is rare, the ECG is a simple, inexpensive and non-invasive investigation which can be the first indicator of serious underlying pathology. While it had been known that most patients would develop their symptoms under stress, it was also known that in a minority of cases these life-threatening cardiac events could occur at rest [1]. Triggers for intense or sudden emotion; activities that are known to precipitate syncopal events in individuals with long QT syndrome, includes: competitive sports, amusement park rides, frightening movies and jumping into cold water [11]. Auditory stimuli such as an alarm clock or a telephone bell, anesthesia, and fever have also been reported as specific triggers [1,5,12]. Drugs that cause further prolongation of the QT interval should be avoided. Some of these are frequently used by children. Among them antibiotics and drugs used against asthma (i.e., erythromycin, terbutaline), should be avoided by these patients [5]. Because JLNS patients are exposed to ventricular arrhythmias, patients should be equipped with paddles for defibrillation during surgery [5]. Careful attentions should be given at the induction of anesthesia and during wake up, when the patient is presumably experiencing most stress [5]. As arrhythmias are triggered by conditions associated with increased sympathetic activity, medication containing sympathomimetic (i.e., epinephrine) should be avoided [5]. Drugs such as Halothane, which sensitize the myocardium to the effect of catecholamine, should also be avoided. Beta-blocker therapy is the first choice for LQTS. It dramatically decreases event rates, from 0.97 to 0.31 events per patient per year [12]. Cardiac events in LQTS patients are generally well controlled with b-blocker therapy. However, patients with a history of aborted cardiac arrest, symptomatic patients in the first year of life, and patients with JLNS carrying KCNQ1 mutations are at particularly high risk and therefore, special aids, including implantable cardioverter defibrillator and left cardiac sympathetic denervation on top of b-blocker therapy may be deemed necessary because of the high recurrence rate of fatal arrhythmia [12]. Besides medical treatment, life-style advice for patients is important [12] and previously described triggers (e.g. jumping into cold water) should be avoided as much as possible. A review of the literature has identified sixteen reports on cochlear implantation in a total of 38 children with JLNS (Table 2) [5–7,13–25]. None of these authors have reported cardiac events during device switch-on. Also, we did not experience such an event during device switch-on in our cases. But, as auditory stimuli is reported to be as specific trigger [1,5,12], we agree with Siem et al. [5] who recommended that the activation of the processor is done during continuous heart monitoring with a defibrillator at hand, preferably at the pediatric intensive care unit. According to Crotti et al. [1] even though the clinical diagnosis of JLNS is rather straightforward, it is important to genotype all these patients because it has been shown that the smaller group with KCNE1 mutations has a markedly less severe clinical course than that with mutations on KCNQ1 which could influence therapeutic management. All of our cases were referred for genetic evaluation but, unfortunately due to its costs only one child took the exam. A review of the literature on sixteen reports of cochlear implantation in a total of 38 children with JLNS
Table 2 Review of literature (implanted cases). Authors
Number of cases
Cardiac events during device switch-on
Gene evaluation
Outcomes of cochlear implant
Baines et al. (1999) Green et al. (2000) Chorbachi et al. (2002) Neamt¸u et al. (2003) Rajput et al. (2003) Berrettini et al. (2003) Daneshi et al. (2007) Siem et al. (2008) Yanmei et al. (2008) Kang et al. (2011) Raghunandhan et al. (2011) Senthil Vadivu et al. (2013) Broomfield et al. (2013)
1 1 2
No data No No
No No Yes
No data Good Good
1 2 1
No No data No
No No data No
Good No data Good
3
No
No
Good
8 1
No No
Yes No
Good Good
1 1
No No data
No No data
No data No data
4
No
No
Good
5
No
No
5
No data
Yes
Two of them died, the rest were good No data
1 1
No data No data
No No
No data No data
Winbo and Rydberg (2015) Kumar et al. (2015) Yadav and Sikka (2015)
[5–7,13–25] revealed that only in three of them gene evaluation were done for their patients (Table 2). For older reports this may be due to unavailability of these tests but for the recent reports, this could be due to its costs especially in developing countries like ours. Nine available reports about the outcome of cochlear implantation in these patients (Table 2) indicated good auditory outcome. All our patients have also shown good performance with their devices. So, as Yanmei and his colleagues [6] have stated, the auditory and language outcome after cochlear implantation in this syndrome at least is not worse than those in patients with nonsyndromic sensorineural deafness. 5. Conclusions Although JLNS is a rare disease, due to its life treatening feature, all congenitally deaf patients should have an ECG taken as a part of their evaluation. As auditory stimuli is reported to be a specific trigger it is prudent that to activate the processor with continuous heart monitoring even though there is no reported cardiac event during device switch-on. Our data as well as the litreature review confirms that cochlear implantation can be performed relatively safely in patients with Jervell and Lange-Nielsen syndrom if necessary precautions have been taken appropriately and their auditory outcome is good. Triggers of the cardiac events should be avoided throughout the life of these patients. Financial disclosure The authors did not have any financial or material support for this work. Conflicts of interest The authors declare that they have no conflict of interest.
A. Eftekharian, M.H. Mahani / International Journal of Pediatric Otorhinolaryngology 79 (2015) 1544–1547
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