Jervell and Lange-Nielson Syndrome masquerading as intractable epilepsy

Goyal, Jagdish Prasad; Sethi, Alka; Shah, VB

doi:10.4103/0972-2327.95003

Cited by 12 publications

(10 citation statements)

References 9 publications

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“…Patients with SADS can present with or be (incorrectly) labelled as having epilepsy. [22][23][24][25] Guidelines on post-mortem examination of SUD in the young have been published by the Royal College of Pathologists of Australasia (https://www.rcpa. edu.au/getattachment/89884c69-f066-411d-a3d1-39460444db13/Guidelines-on-Autopsy-Practice.…”

Section: Discussionmentioning

confidence: 99%

Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives

et al. 2019

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Objective: Sudden arrhythmia death syndrome (SADS) accounts for about 30% of causes of sudden cardiac death (SCD) in young people. In Hong Kong, there are scarce data on SADS and a lack of experience in molecular autopsy. We aimed to investigate the value of molecular autopsy techniques for detecting SADS in an East Asian population. Methods:This was a two-part study. First, we conducted a retrospective 5-year review of autopsies performed in public mortuaries on young SCD victims. Second, we conducted a prospective 2-year study combining conventional autopsy investigations, molecular autopsy, and cardiac evaluation of the first-degree relatives of SCD victims. A panel of 35 genes implicated in SADS was analysed by next-generation sequencing.Results: There were 289 SCD victims included in the 5-year review. Coronary artery disease was the major cause of death (35%); 40% were structural heart diseases and 25% were unexplained. These unexplained cases could include SADS-related conditions. In the 2-year prospective study, 21 SCD victims were examined: 10% had arrhythmogenic right ventricular cardiomyopathy, 5% had hypertrophic cardiomyopathy, and 85% had negative autopsy. Genetic analysis showed 29% with positive heterozygous genetic variants; six variants were novel. One third of victims had history of syncope, and 14% had family history of SCD. More than half of the 11 first-degree relatives who underwent genetic testing carried related genetic variants, and 10% had SADS-related clinical features. Conclusion: This pilot feasibility study shows the value of incorporating cardiac evaluation of Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and twoyear prospective molecular autopsy study by nextgeneration sequencing and clinical evaluation of their first-degree relativesNew knowledge added by this study • This study provides important data on the prevalence and types of sudden arrhythmia death syndrome (SADS) among young victims of sudden cardiac death in an East Asian population. • This is the first local feasibility study on the service model incorporating cardiac evaluation of surviving relatives and molecular autopsy by next-generation sequencing into the conventional forensic investigations. Implications for clinical practice or policy • Genomic testing should be conducted on patients with cardiomyopathies and channelopathies.• Clinical assessment should be provided for at-risk family members irrespective of genetic findings.• Molecular autopsy together with conventional autopsy conducted by qualified pathologists should be applied to victims of SADS, sudden unexpected death in epilepsy, or sudden infant death syndrome.

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Section: Discussionmentioning

confidence: 99%

Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives

et al. 2019

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“…Qureshi et al [] reported compound heterozygous mutations in a consanguineous Indian family with JLNS. Reports of other Indian patients with JLNS also note consanguinity in all; though molecular studies were not performed [Sundar et al, ; Sathyamurthy et al, ; Goyal et al, ]. Patients of Indian ethnicity with AR RWS have not been described till date.…”

Section: Discussionmentioning

confidence: 99%

KCNQ1 mutations associated with Jervell and Lange–Nielsen syndrome and autosomal recessive Romano–Ward syndrome in India—expanding the spectrum of long QT syndrome type 1

Vyas

Puri

Namboodiri

et al. 2016

American J of Med Genetics Pt A

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Long QT syndrome type 1 (LQT1) is the most common type of all Long QT syndromes (LQTS) and occurs due to mutations in KCNQ1. Biallelic mutations with deafness is called Jervell and Lange-Nielsen syndrome (JLNS) and without deafness is autosomal recessive Romano-Ward syndrome (AR RWS). In this prospective study, we report biallelic mutations in KCNQ1 in Indian patients with LQT1 syndrome. Forty patients with a clinical diagnosis of LQT1 syndrome were referred for molecular testing. Of these, 18 were excluded from the analysis as they did not fulfill the inclusion criteria of broad T wave ECG pattern of the study. Direct sequencing of KCNQ1 was performed in 22 unrelated probands, parents and at-risk family members. Mutations were identified in 17 patients, of which seven had heterozygous mutations and were excluded in this analysis. Biallelic mutations were identified in 10 patients. Five of 10 patients did not have deafness and were categorized as AR RWS, the rest being JLNS. Eight mutations identified in this study have not been reported in the literature and predicted to be pathogenic by in silico analysis. We hypothesize that the homozygous biallelic mutations identified in 67% of families was due to endogamous marriages in the absence of consanguinity. This study presents biallelic gene mutations in KCNQ1 in Asian Indian patients with AR JLNS and RWS. It adds to the scant worldwide literature of mutation studies in AR RWS. © 2016 Wiley Periodicals, Inc.

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“… 27. , 28. ] A concerted effort across the nation to gather existing data, plug the gaps in clinical evaluation and proceed with genetic counseling and testing is the way forward in this era where research-based as well as commercial genotyping opportunities with sound bioinformatics backing are currently more readily available.…”

Section: Diagnostic Evolutionmentioning

confidence: 99%

Channelopathies - Emerging Trends in The Management of Inherited Arrhythmias

Chockalingam¹,

Mizusawa

Wilde

2015

Indian Pacing and Electrophysiology Journal

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In spite of their relative rarity, inheritable arrhythmias have come to the forefront as a group of potentially fatal but preventable cause of sudden cardiac death in children and (young) adults. Comprehensive management of inherited arrhythmias includes diagnosing and treating the proband and identifying and protecting affected family members. This has been made possible by the vast advances in the field of molecular biology enabling better understanding of the genetic underpinnings of some of these disease groups, namely congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome. The ensuing knowledge of the genotype-phenotype correlations enables us to risk-stratify, prognosticate and treat based on the genetic test results. The various diagnostic modalities currently available to us, including clinical tools and genetic technologies, have to be applied judiciously in order to promptly identify those affected and to spare the emotional burden of a potentially lethal disease in the unaffected individuals. The therapeutic armamentarium of inherited arrhythmias includes pharmacological agents, device therapies and surgical interventions. A treatment strategy keeping in mind the risk profile of the patients, the local availability of drugs and the expertise of the treating personnel is proving effective. While opportunities for research are numerous in this expanding field of medicine, there is also tremendous scope for incorporating the emerging trends in managing patients and families with inherited arrhythmias in the Indian subcontinent.

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Jervell and Lange-Nielson Syndrome masquerading as intractable epilepsy

Cited by 12 publications

References 9 publications

Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives

Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives

KCNQ1 mutations associated with Jervell and Lange–Nielsen syndrome and autosomal recessive Romano–Ward syndrome in India—expanding the spectrum of long QT syndrome type 1

Channelopathies - Emerging Trends in The Management of Inherited Arrhythmias

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