Jervell-Lange Nielsen syndrome in a family with the Long QT Syndrome (LQTS)
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《美国医学杂志》
1 Department of Cardiovascular and Thoracic Surgery IPGMER & SSKM hospital, Kolkata, India
2 Department of Pediatrics Medicine, IPGMER & SSKM hospital, Kolkata, India
Abstract
A child with Jervell-Lange Nielsen syndrome is presented from Kolkata. Family study showed that the other family members are suffering from long QT syndrome. The child had frequent syncopal attack and very prolonged QT interval requiring left cardiac sympathetic denervation and beta-blocker therapy as patient could not afford implantable defibrillator and cardiac pacing.
Keywords: LQTS, QTc interval, Jervell and Lange-Nielsen syndrome
The long QT syndrome (LQTS) is characterized by prolonged QT interval, syncopal spells, and sudden death from ventricular arrhythmia.[1] They usually manifest by syncope, seizures or palpitation with emotion or exercise.[1] LQTS may be congenital or acquired.[1] Congenital LQTS again may be of three types; Jervell and Lange-Nielsen syndrome, Romano-Ward syndrome More Details and sporadic variety of LQT syndrome.[2] Only Jervell and Lange-Nielsen syndrome have associated congenital deafness.[1] The patient with frequent syncopal attack and very prolonged QTc usually require beta-blocker along with either demand cardiac pacing or left cardiac sympathetic denervation. Patient with asymptomatic LQTS are usually managed with beta-blocker medication.
Case report
A 10-year-old boy was admitted in our institute with a history of recurrent convulsions and syncopal attacks since infancy. Chest pain and circum oral pallor usually preceded the syncopal attacks. The child was deaf and mute since birth. He also had mild degree of delayed development. He was diagnosed as a case of delayed development with seizure disorder before. This child was born at term at home and did not have birth asphyxia. There was no history of consanguinity. Mother had history of chicken pox at first trimester of pregnancy. There was history of similar illness in elder brother who died at the age of three years from "sudden death". Another elder sister and younger brother remained asymptomatic.
The child had significant failure to thrive with mild pallor. His pulse was regular with normal volume 102/min and equally palpable in all four limbs. The blood pressure was normal (100/72 mm of Hg). His systemic examination was within normal limit except evidence of deafness.
Investigation revealed presence of hypo-chromic microcytic anemia with normal serum electrolytes and blood glucose level. Chest X-ray was normal. Thyroid profile showed normal values. Computed tomography (CT) scan of brain revealed normal study.
He also had an electroencephalogram (EEG) suggestive of dys-arrhythmia and an auditory brainstem responses (ABR) study suggestive of sensorineural deafness. His echocardiography was normal. Electrocardiogram (ECG) tracing Figure1 at admission showed heat rate of 100/min, rhythm regular, axis-+45°, QTc-720ms with biphasic T wave. ECG tracing after putting the child on beta-blocker showed heart rate of 78/min, rhythm regular, axis-+45°, QTc-680ms, with abnormal T Wave Figure2. Family screening for LQTS showed sister Figure3 of patient has heart rate of 110/min, rhythm regular, axis-+60°, QTc-540ms, with normal T Wave. ECG tracing of younger brother Figure4 of patient revealed heart rate of 120/min, rhythm regular, axis-+75°, QTc-480ms, with normal T Wave. ECG tracing of father Figure5 of patient showed heart rate of 82/m, rhythm- regular, axis-+75°, QTc-460ms, T wave-normal. ECG tracing of mother Figure6 of patient showed heart rate of 92/m, rhythm- regular, axis-+30°, QTc-500ms, T wave-normal.
The asymptomatic sister, brother and mother with long QT were put on beta-blocker therapy. The child was put on beta-blocker therapy after left cardiac sympathetic denervation in view of very long QT interval with multiple poor risk factors for sudden death as the patient could not afford implantable defibrillator and cardiac pacing.
Discussion
Jervell and Lange-Nielsen syndrome was first described in 1957 from Norway.[3] It is transmitted by autosomal recessive manner. Here the excessive activity of left stellate ganglion with subnormal activity of right stellate ganglion seems to be responsible for prolongation of QT interval.[1] It usually has positive family history in 60% of cases. Recent study has identified specific gene abnormality that encodes ion channels responsible for LQTS and deafness.[2]
The electrocardiographic tracing showed prolong QT interval (>460 ms) with abnormal T wave morphology (bifid, biphasic, notched etc). It may also reveal bradicardia, AV block, premature ventricular contraction or polymorphic ventricular tachycardia.[4]
The Pediatric Electrophysiology Society in 1993 has defined the following diagnostic criteria for diagnosis;
a) The presence of a prolonged QTc interval of >. 44(440ms) second in the absence of other underlying causes such as prematurity, electrolyte imbalance etc, b) A positive family history of long QT syndrome plus unexplained syncope, seizure, or cardiac arrest associated with typical inciting events such as exercise or emotion.[5]
The absolute risk factors associated with LQTS for sudden death include bradycardia, very prolonged QTc interval (>.55 second [550 ms]), symptomatic at presentation, younger age at presentation (<1 month) and documented ventricular fibrillation.[6] The relative risk factors are T-wave alternation and non-compliance with medication.[7]
Our patient belongs to Jervell and Lange-Nielsen syndrome as he fulfills the criteria for LQTS as per Pediatric Electrophysiological Society and also had congenital deafness.
The other family members had asymptomatic LQTS. The treatment modality in LQTS includes; a) Intracardiac defibrillator, modality of choice for most severe patients with multiple risk factors, b) Beta-blocker; in asymptomatic mild LQTS and c) Left cardiac sympathetic denervation along with beta blocker for symptomatic patients who cannot afford cardiac pacing.[8] Overall LQTS have poor prognosis with mortality rate of about 80% in untreated patients and adjusted annual mortality of 4.5% with treatment.[9]
We have put all the family members on beta-blockers therapy, as they remain asymptomatic with regular follow-up. Since the patient could not afford intracardiac defibrillator which is the best modality of treatment available, he was managed with left cardiac sympathetic denervation along with beta-blocker therapy. Subsequent ECG Figure7 immediate after left cardiac sympathetic denervation showed heart rate of 72/m, rhythm- regular, axis-+45°, QTc-600ms, T wave- abnormal. The child was continued on beta-blocker therapy on follow-up. In short follow-up so far, he has shown improvement, as he become more active, doing routine work comfortably, no recurrence of syncope and parents are also very happy. QT interval have shortened by 120 msec(720-600) from that of pretreatment level, though our aim is to bring it down to near normal at least below 550 msec to minimize the risk of sudden death.[1] There was one report of Jervell-Lange Nielsen syndrome from a Pakistani family in 2004.[10] In the best of our knowledge, there was no report of any family with Jervell-Lange Nielsen syndrome the long QT syndrome (LQTS) from India before.
References
1. Park MK, Troxler RG; Syncope. In Pediatric Cardiology for Practioners Park MK, Troxler RG Eds; 4th edition, Mosby Inc, St. Louis, Missouri: 2002; 449-459.
2. Chiang CE, Roden DM. The long QT syndromes: genetic basis and clinical implications. J Am Coll Cardiol 2000; 36 : 1-12.
3. Garson A Jr, Dick M II, Fournier A et al. The long QT syndrome in children: An international study of 287 patients. Circulation; 1993; 87: 1866-1872.
4. Hiejima K, Suzuki F, Satake S, Ishihara K. Electrophysiologic studies of Jervell, Lange-Nielsen syndrome. Chest 1981; 79: 446-448.
5. Guntheroth WG: Long QT syndrome in children [editorial]. Circulation 1993; 87; 2058-2059.
6. Salen P, Nadkarni V. Congenital long-QT syndrome: a case report illustrating diagnostic pitfalls. J Emerg Med 1999; 17: 859-864.
7. Komsuoglu B, Goldeli O, Kulan K, Budak F, Gedik Y, Tuncer C, Komsuoglu SS. The Jervell and Lange-Nielsen syndrome: Int J Cardiol 1994; 47 : 189-192.
8. Schwartz PJ, Locati EH, Moss AJ et al. Left sympathetic denervation in the therapy of congenital long QT syndrome: a worldwide report. Circulation 1991; 84 : 503-511.
9. Schwartz PJ, Stramba-Badiale M, Segantini A et al. Prolongation of the QT interval and the sudden infant death syndrome. N Eng J Med 1998; 338 : 1709-1714.
10. Yuen LK, Fong NC, Tang PM, Shek CC, Chow CB. Jervell-Lange Nielsen syndrome in a Pakistani family. Hong Kong Med J 2004; 10 : 351-354.(Mondal RK, Karmakar B, Ch)
2 Department of Pediatrics Medicine, IPGMER & SSKM hospital, Kolkata, India
Abstract
A child with Jervell-Lange Nielsen syndrome is presented from Kolkata. Family study showed that the other family members are suffering from long QT syndrome. The child had frequent syncopal attack and very prolonged QT interval requiring left cardiac sympathetic denervation and beta-blocker therapy as patient could not afford implantable defibrillator and cardiac pacing.
Keywords: LQTS, QTc interval, Jervell and Lange-Nielsen syndrome
The long QT syndrome (LQTS) is characterized by prolonged QT interval, syncopal spells, and sudden death from ventricular arrhythmia.[1] They usually manifest by syncope, seizures or palpitation with emotion or exercise.[1] LQTS may be congenital or acquired.[1] Congenital LQTS again may be of three types; Jervell and Lange-Nielsen syndrome, Romano-Ward syndrome More Details and sporadic variety of LQT syndrome.[2] Only Jervell and Lange-Nielsen syndrome have associated congenital deafness.[1] The patient with frequent syncopal attack and very prolonged QTc usually require beta-blocker along with either demand cardiac pacing or left cardiac sympathetic denervation. Patient with asymptomatic LQTS are usually managed with beta-blocker medication.
Case report
A 10-year-old boy was admitted in our institute with a history of recurrent convulsions and syncopal attacks since infancy. Chest pain and circum oral pallor usually preceded the syncopal attacks. The child was deaf and mute since birth. He also had mild degree of delayed development. He was diagnosed as a case of delayed development with seizure disorder before. This child was born at term at home and did not have birth asphyxia. There was no history of consanguinity. Mother had history of chicken pox at first trimester of pregnancy. There was history of similar illness in elder brother who died at the age of three years from "sudden death". Another elder sister and younger brother remained asymptomatic.
The child had significant failure to thrive with mild pallor. His pulse was regular with normal volume 102/min and equally palpable in all four limbs. The blood pressure was normal (100/72 mm of Hg). His systemic examination was within normal limit except evidence of deafness.
Investigation revealed presence of hypo-chromic microcytic anemia with normal serum electrolytes and blood glucose level. Chest X-ray was normal. Thyroid profile showed normal values. Computed tomography (CT) scan of brain revealed normal study.
He also had an electroencephalogram (EEG) suggestive of dys-arrhythmia and an auditory brainstem responses (ABR) study suggestive of sensorineural deafness. His echocardiography was normal. Electrocardiogram (ECG) tracing Figure1 at admission showed heat rate of 100/min, rhythm regular, axis-+45°, QTc-720ms with biphasic T wave. ECG tracing after putting the child on beta-blocker showed heart rate of 78/min, rhythm regular, axis-+45°, QTc-680ms, with abnormal T Wave Figure2. Family screening for LQTS showed sister Figure3 of patient has heart rate of 110/min, rhythm regular, axis-+60°, QTc-540ms, with normal T Wave. ECG tracing of younger brother Figure4 of patient revealed heart rate of 120/min, rhythm regular, axis-+75°, QTc-480ms, with normal T Wave. ECG tracing of father Figure5 of patient showed heart rate of 82/m, rhythm- regular, axis-+75°, QTc-460ms, T wave-normal. ECG tracing of mother Figure6 of patient showed heart rate of 92/m, rhythm- regular, axis-+30°, QTc-500ms, T wave-normal.
The asymptomatic sister, brother and mother with long QT were put on beta-blocker therapy. The child was put on beta-blocker therapy after left cardiac sympathetic denervation in view of very long QT interval with multiple poor risk factors for sudden death as the patient could not afford implantable defibrillator and cardiac pacing.
Discussion
Jervell and Lange-Nielsen syndrome was first described in 1957 from Norway.[3] It is transmitted by autosomal recessive manner. Here the excessive activity of left stellate ganglion with subnormal activity of right stellate ganglion seems to be responsible for prolongation of QT interval.[1] It usually has positive family history in 60% of cases. Recent study has identified specific gene abnormality that encodes ion channels responsible for LQTS and deafness.[2]
The electrocardiographic tracing showed prolong QT interval (>460 ms) with abnormal T wave morphology (bifid, biphasic, notched etc). It may also reveal bradicardia, AV block, premature ventricular contraction or polymorphic ventricular tachycardia.[4]
The Pediatric Electrophysiology Society in 1993 has defined the following diagnostic criteria for diagnosis;
a) The presence of a prolonged QTc interval of >. 44(440ms) second in the absence of other underlying causes such as prematurity, electrolyte imbalance etc, b) A positive family history of long QT syndrome plus unexplained syncope, seizure, or cardiac arrest associated with typical inciting events such as exercise or emotion.[5]
The absolute risk factors associated with LQTS for sudden death include bradycardia, very prolonged QTc interval (>.55 second [550 ms]), symptomatic at presentation, younger age at presentation (<1 month) and documented ventricular fibrillation.[6] The relative risk factors are T-wave alternation and non-compliance with medication.[7]
Our patient belongs to Jervell and Lange-Nielsen syndrome as he fulfills the criteria for LQTS as per Pediatric Electrophysiological Society and also had congenital deafness.
The other family members had asymptomatic LQTS. The treatment modality in LQTS includes; a) Intracardiac defibrillator, modality of choice for most severe patients with multiple risk factors, b) Beta-blocker; in asymptomatic mild LQTS and c) Left cardiac sympathetic denervation along with beta blocker for symptomatic patients who cannot afford cardiac pacing.[8] Overall LQTS have poor prognosis with mortality rate of about 80% in untreated patients and adjusted annual mortality of 4.5% with treatment.[9]
We have put all the family members on beta-blockers therapy, as they remain asymptomatic with regular follow-up. Since the patient could not afford intracardiac defibrillator which is the best modality of treatment available, he was managed with left cardiac sympathetic denervation along with beta-blocker therapy. Subsequent ECG Figure7 immediate after left cardiac sympathetic denervation showed heart rate of 72/m, rhythm- regular, axis-+45°, QTc-600ms, T wave- abnormal. The child was continued on beta-blocker therapy on follow-up. In short follow-up so far, he has shown improvement, as he become more active, doing routine work comfortably, no recurrence of syncope and parents are also very happy. QT interval have shortened by 120 msec(720-600) from that of pretreatment level, though our aim is to bring it down to near normal at least below 550 msec to minimize the risk of sudden death.[1] There was one report of Jervell-Lange Nielsen syndrome from a Pakistani family in 2004.[10] In the best of our knowledge, there was no report of any family with Jervell-Lange Nielsen syndrome the long QT syndrome (LQTS) from India before.
References
1. Park MK, Troxler RG; Syncope. In Pediatric Cardiology for Practioners Park MK, Troxler RG Eds; 4th edition, Mosby Inc, St. Louis, Missouri: 2002; 449-459.
2. Chiang CE, Roden DM. The long QT syndromes: genetic basis and clinical implications. J Am Coll Cardiol 2000; 36 : 1-12.
3. Garson A Jr, Dick M II, Fournier A et al. The long QT syndrome in children: An international study of 287 patients. Circulation; 1993; 87: 1866-1872.
4. Hiejima K, Suzuki F, Satake S, Ishihara K. Electrophysiologic studies of Jervell, Lange-Nielsen syndrome. Chest 1981; 79: 446-448.
5. Guntheroth WG: Long QT syndrome in children [editorial]. Circulation 1993; 87; 2058-2059.
6. Salen P, Nadkarni V. Congenital long-QT syndrome: a case report illustrating diagnostic pitfalls. J Emerg Med 1999; 17: 859-864.
7. Komsuoglu B, Goldeli O, Kulan K, Budak F, Gedik Y, Tuncer C, Komsuoglu SS. The Jervell and Lange-Nielsen syndrome: Int J Cardiol 1994; 47 : 189-192.
8. Schwartz PJ, Locati EH, Moss AJ et al. Left sympathetic denervation in the therapy of congenital long QT syndrome: a worldwide report. Circulation 1991; 84 : 503-511.
9. Schwartz PJ, Stramba-Badiale M, Segantini A et al. Prolongation of the QT interval and the sudden infant death syndrome. N Eng J Med 1998; 338 : 1709-1714.
10. Yuen LK, Fong NC, Tang PM, Shek CC, Chow CB. Jervell-Lange Nielsen syndrome in a Pakistani family. Hong Kong Med J 2004; 10 : 351-354.(Mondal RK, Karmakar B, Ch)