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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 11  |  Issue : 3  |  Page : 179-181

Long QT syndrome: Presenting as fetal bradycardia


Department of Neonatology, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai, Tamil Nadu, India

Date of Submission28-Dec-2021
Date of Decision28-Mar-2022
Date of Acceptance21-Apr-2022
Date of Web Publication06-Jul-2022

Correspondence Address:
Premkumar Segaran
Department of Neonatology, Institute of Child Health and Hospital for Children, Egmore, Chennai - 600 008, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.jcn_147_21

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  Abstract 


Long QT syndromes (LQTSs) are inherited disorders of abnormal myocardial repolarization. It is characterized by prolonged QT interval, T wave abnormalities, and tachyarrhythmias such as Torsade de Pointes. Previous literature on congenital LQTS in neonates had reported presentations of cardiac arrhythmias leading to sudden death in the postnatal period. We present here a case of a neonate who presented initially with fetal bradycardia; postnatally developed ventricular tachyarrhythmias which after stabilization showed prolonged QT interval in electrocardiography leading to the diagnosis of LQTS due to a rare mutation in the ankyrin B gene. Acute ventricular tachyarrhythmia was managed with lidocaine and magnesium infusion. We used propranolol to sustain the reduction in QT interval to prevent tachyarrhythmias and Torsades de Pointes and thereby sudden death. On follow-up, the infant showed normal growth and neurodevelopment with QT interval maintained below 500 ms on propranolol prophylaxis. Fetal bradycardia can also be one of the initial manifestations of LQTS due to rare genetic mutations involving the ankyrin B gene.

Keywords: Ankyrin B gene, fetal bradycardia, long QT syndrome, neonatal, tachyarrhythmias


How to cite this article:
Segaran P, Kamalarathnam C N, Murugesan A, Mariappan V. Long QT syndrome: Presenting as fetal bradycardia. J Clin Neonatol 2022;11:179-81

How to cite this URL:
Segaran P, Kamalarathnam C N, Murugesan A, Mariappan V. Long QT syndrome: Presenting as fetal bradycardia. J Clin Neonatol [serial online] 2022 [cited 2022 Oct 1];11:179-81. Available from: https://www.jcnonweb.com/text.asp?2022/11/3/179/350030




  Introduction Top


Long QT syndrome (LQTS) was the first cardiac channelopathy to be described and the most extensively investigated arrhythmogenic ion channel disorder to date. The prevalence is approximately 1in 2500.[1] It is an arrhythmogenic disorder characterized by prolonged QT interval and T wave abnormalities on electrocardiography (ECG) that are associated with tachyarrhythmias, typically ventricular Torsade de Pointes (TdP). LQTS Type 4 is a very rare variant accounting for <1% of the cases of congenital LQTS. LQTS 4 due to ANKB gene mutation is the first nonion channel gene mutation causing LQTS. It is caused by an autosomal dominant mutation in the ANKB gene present, i.e., chromosome 4q25–27[2] encoding for the structural protein ankyrin-β. Mutation impairs the function of the ANKB gene. Ankyrin B links the cardiac myocyte membrane proteins to the cytoskeletal proteins. This protein binds to several ion channel proteins such as Na/ATPase, Na/Ca exchanger, and inositol triphosphate receptor. The loss of these ion proteins and the subsequent increase in the intracellular calcium concentration causes early and delayed after depolarization, leading to a wide range of arrhythmias including catecholaminergic polymorphic ventricular tachycardia, atrial fibrillation, sinus node dysfunction, and bradycardia.[3]


  Case Report Top


Baby X born to 24-year-old G2P2 with uneventful 1st and 2nd trimesters presented with fetal bradycardia and 2:1 AV block without hydrops at 34 weeks of gestation during the antenatal scan. Subsequent scans at 36 weeks of gestation revealed normal heart rate and rhythm with no AV dissociation. Fetal growth was normal during the entire period. He was delivered by normal vaginal delivery as a full-term male neonate weighing 3080 g and had a normal transition at birth. The baby had incessant cry and tachycardia at 47 h of life and was diagnosed to have ventricular tachyarrhythmias, which were managed with intravenous magnesium and lidocaine. The baby was referred to our hospital for further management.

At admission, the baby was hemodynamically stable with a heart rate ranging from 90 to 130 beats per min, regular in rhythm, normal in volume, and no features suggestive of cardiac failure. Physical examination was normal without any obvious external congenital malformations or dysmorphism, and nothing abnormal was detected during the examination of cardiovascular, respiratory systems, and abdominal examination. First-line investigations ruled out dyselectrolytemia, sepsis, and hypoglycemia. ECG showed a prolonged QTc interval of 550 ms with 1:1 conduction with isoelectric ST-segment and normal T wave [Figure 1]. Echocardiography revealed a structurally normal heart. Clinical exome sequencing done revealed a heterozygous missense variant in ANK2 gene (c.5152G>A; p. Gly1718Ser), which codes for the structural protein ankyrin-β. Hearing assessed by brainstem evoked response audiometry was normal in the infant. The maternal antinuclear antibody screen was negative. There was no family history of cardiac arrhythmias, sudden death, or deafness. Both parents and the elder sibling had normal ECG patterns during screening for LQTS.
Figure 1: ECG showing prolonged QT interval. QTc = 550 ms. ECG: Electrocardiography

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After the cardiologist consultation, the baby was started on oral propranolol prophylactically at 1 mg/kg/day to decrease the duration of QT interval, which would prevent further occurrence of ventricular tachyarrhythmias and thereby sudden death in the future. Even in infants with a very prolonged QT interval, it is expected to shorten by 1 month of age. In our baby, the Qtc interval was shortened in a dose-dependent manner by gradually increasing the dose of propranolol. The infant required an increased dosage of up to 3 mg/kg/day in three divided doses for achieving a target QTc interval of <500 ms. On this high dose of propranolol, the infant maintained sinus rhythm, QTc interval was reduced to 490 ms to prevent further episodes of ventricular tachyarrhythmias during hospitalization. The baby was discharged on oral propranolol at 3 mg/kg/day in sinus rhythm, QTc interval 490 ms, isoelectric ST-segment, and normal T wave after 25 days of hospitalization. Parents were educated about the drugs which should be avoided, as they may prolong QT intervals and avoid strenuous exercises in the future. Mutation analysis for the parents was planned at a later date due to economic constraints.

Postdischarge on follow-up at 4 months of age, the baby had normal physical growth and neurodevelopment, with QTc interval maintained at <500 ms. There was no history of acute life-threatening events after discharge.


  Discussion Top


Our case represents the fetal presentation of LQTS, with transient intrauterine bradycardia, AV block, and no hydrops. The baby developed ventricular tachyarrhythmia progressing to TdP in the early postnatal period, requiring lidocaine and magnesium sulfate infusion. Prompt diagnosis and early treatment with propranolol prevented further episodes of tachyarrhythmias and gradually reduced the QT interval. Prenatal diagnosis of LQTS should be suspected when there is fetal bradycardia, second-degree heart block, or ventricular arrhythmia, usually associated with hydrops.[4],[5] As per the study by Ishikawa et al., LQTS accounts for 15%–17% of fetal bradycardia <110 BPM and 6%–50% of fetal AV block among the fetuses with a normally structured heart. Antenatally LQTS can be diagnosed by doing fetal ECG or magnetocardiography.[6]

Although more than 500 mutations distributed in 10 genes have been described to cause cLQTS, almost 90% are due to KCNQ1 (LQTS 1), KCNH2 (LQTS 2), or SCN5A (LQTS 3). In our case, ANK B gene mutation was identified which accounts for a very rare variant of cLQTS, accounting for <1% of cases.[3] It accounts for a very rare variant of cLQTS, accounting for <1% of cases.[3] It causes a wide range of arrhythmias including TdP, atrial fibrillation, AV block, sinus node dysfunction, and bradycardia. Even when the parents are unaffected or family history is unremarkable, genetic testing may still be of value to support the clinical diagnosis, to confirm de novo onset of disease, and to identify the variant of LQTS which may benefit from the addition of sodium channel blocker.[7]

A high index of suspicion for LQTS should be considered in fetuses with fetal bradycardia, irrespective of the presence or absence of a family history of LQTS along with other common causes of rhythm and conduction abnormalities. Even though literature says early neonatal manifestation of LQTS was strongly associated with major events such as syncope, cardiac arrest, and sudden death, our case responded well to oral propranolol leading to QTc shortening and 1:1 atrioventricular conduction and without any ventricular arrhythmias.

Implantable cardioverter-defibrillator (ICD) is indicated for patients who failed beta-blocker therapy and have a high risk for sudden cardiac death.[8] Considering that the baby did well on medical therapy and had no recurrences while in the hospital or after discharge, the risk of an ICD outweighed the potential benefit in our patient. Left cardiac sympathetic denervation is warranted when β-blockers and ICD fail. Administration of prenatal β-adrenergic blockers can improve the postnatal outcome of LQTS when they are diagnosed antenatally. Thus, early diagnosis and starting on β-blockers irrespective of symptoms or age, even in the prenatal stage, with titrating to the highest tolerated dose may prevent the major cardiac event from 73% to 6%.


  Conclusion Top


The primary aim of this case is to create awareness about congenital LQTS as one of the causes of fetal bradycardia. Even though cLQTS is relatively rare, recognizing this entity is of great importance because early intervention and treatment can avoid the patient's sudden death.

Acknowledgments

I thank Drs Ramya, Anto ferdine vaik, Saravanan, Himanshu Sharma, Bhaskara Reddy,

Anil Kumar Varma, and Niranjan for their support. I am also thankful all PGs and staffs involved in the treatment of babies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Johnson JN, Ackerman MJ. QTc: How long is too long? Br J Sports Med 2009;43:657-62.  Back to cited text no. 1
    
2.
Yong S, Tian X, Wang Q. LQT4 gene: The “missing” ankyrin. Mol Interv 2003;3:131-6.  Back to cited text no. 2
    
3.
Medeiros-Domingo A, Iturralde-Torres P, Ackerman MJ. Clinical and genetic characteristics of long QT syndrome. Rev Esp Cardiol 2007;60:739-52.  Back to cited text no. 3
    
4.
Chang IK, Shyu MK, Lee CN, Kau ML, Ko YH, Chow SN, et al. Prenatal diagnosis and treatment of fetal long QT syndrome: A case report. Prenat Diagn 2002;22:1209-12.  Back to cited text no. 4
    
5.
Hosono T, Kawamata K, Chiba Y, Kandori A, Tsukada K. Prenatal diagnosis of long QT syndrome using magnetocardiography: A case report and review of the literature. Prenat Diagn 2002;22:198-200.  Back to cited text no. 5
    
6.
Ishikawa S, Yamada T, Kuwata T, Morikawa M, Yamada T, Matsubara S, et al. Fetal presentation of long QT syndrome-evaluation of prenatal risk factors: A systematic review. Fetal Diagn Ther 2013;33:1-7.  Back to cited text no. 6
    
7.
Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, et al. Risk stratification in the long-QT syndrome. N Engl J Med 2003;348:1866-74.  Back to cited text no. 7
    
8.
Horner JM, Kinoshita M, Webster TL, Haglund CM, Friedman PA, Ackerman MJ. Implantable cardioverter defibrillator therapy for congenital long QT syndrome: A single-center experience. Heart Rhythm 2010;7:1616-22.  Back to cited text no. 8
    


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