Year : 2021  |  Volume : 14  |  Issue : 3  |  Page : 443--448

Initial experience and results of a cardiogenetic clinic in a tertiary cardiac care center in India

Saileela Rajan1, Priya Chockalingam2, Nageswara Rao Koneti3, Thenral S Geetha4, Sanghamitra Mishra4, Calambur Narasimhan5,  
1 Department of Pediatric Cardiology, MIOT Centre for Children's Cardiac Care, MIOT Hospitals, Chennai, Tamil Nadu, India
2 Cardiac Wellness Institute, Chennai, Tamil Nadu, India
3 Department of Pediatric Cardiology, Rainbow Children's Heart Institute, Hyderabad, Telangana, India
4 MedGenome Labs Ltd., Bengaluru, Karnataka, India
5 Department of Cardiology, Division of Cardiac Electrophysiology, AIG Hospital, Hyderabad, Telangana, India

Correspondence Address:
Saileela Rajan
Department of Pediatric Cardiology, MIOT Centre for Children's Cardiac Care, MIOT Hospitals, Chennai, Tamil Nadu

How to cite this article:
Rajan S, Chockalingam P, Koneti NR, Geetha TS, Mishra S, Narasimhan C. Initial experience and results of a cardiogenetic clinic in a tertiary cardiac care center in India.Ann Pediatr Card 2021;14:443-448

How to cite this URL:
Rajan S, Chockalingam P, Koneti NR, Geetha TS, Mishra S, Narasimhan C. Initial experience and results of a cardiogenetic clinic in a tertiary cardiac care center in India. Ann Pediatr Card [serial online] 2021 [cited 2022 Dec 7 ];14:443-448
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Cardiogenetic clinics have gained importance over the past two decades due to their ability to integrate genetic medicine with clinical cardiology and thereby provide comprehensive care to affected patients and their families.[1],[2] A multidisciplinary team approach comprising the cardiologist, electrophysiologist, and clinical geneticist has resulted in significant changes in the management of children with inherited cardiac disorders. However, the concept of cardiogenetic clinic is not yet part of mainstream pediatric cardiology practice in developing countries. This may be attributed to the busy outpatient clinics, lack of personnel, cost constraints, and complexities of genetic testing. We share our early experience on the conduct and yield of the cardiogenetic clinic at our institute.

 Establishment and Conduct of Cardiogenetic Clinic

A cardiogenetic clinic was started in January 2015 at CARE Hospital, a tertiary cardiac care center in Hyderabad, India. Patients were recruited from the Pediatric Cardiology and Electrophysiology Departments. Eligible patients registered in the clinic included patients with (i) cardiomyopathy with one other affected family member (sibling/parent), (ii) history and electrocardiogram suggestive of channelopathy, and (iii) other cardiac disorders suspected to have a genetic basis.

A detailed clinical history, family history, electrocardiogram and echocardiogram of the patient and the family members were obtained. Pretest counseling was done by a multidisciplinary team consisting of pediatric cardiologist, electrophysiologist, and clinical and molecular geneticists. Following written informed consent, blood samples were drawn from the index patient, parents, and family members whenever feasible. DNA extracted from blood was used to perform whole-exome analysis using Agilent SureSelect (Santa Clara, CA) Human All Exome kit v5 (50 Mb). Posttest counseling was offered to the families.

 Genetic Results

From January to December 2015, 26 patients were registered in the cardiogenetic clinic. Of them, 14 consented for genetic evaluation. The age of the cohort ranged from 7 months to 27 years (median 7 years; eight males). The baseline characteristics of the index patients are depicted in [Table 1]. A total of 56 patients, including index patients (n = 14, probands) and their family members (n = 42), were subjected to genetic testing. Significant variants (pathogenic/likely pathogenic) were detected in 7/14 probands and clinically correlating variants in known genes, whose significance is not known (variants of uncertain significance [VUS]), were detected in 4/14 probands and no significant variants in 3/14 cases [Table 2].{Table 1}{Table 2}

The cohort was classified into three groups based on the clinical diagnosis.

Group I (Cardiomyopathies)

Of the eight patients in this group, dilated cardiomyopathy (DCM) was present in six and hypertrophic cardiomyopathy (HCM) and ventricular noncompaction in one patient each. Among those with DCM, five patients had variants in genes that are known to cause cardiomyopathy. Patient 7 with asymptomatic ventricular noncompaction showed no pathogenic gene variant. Patient 8 was diagnosed to have obstructive HCM in her infancy during family screening, as her father was being treated for HCM. Her genetic report showed a heterozygous missense variation in the MYH7 gene, which was also detected in the father. The disease had an autosomal dominant inheritance, but the clinical and echocardiographic presentation was different in the index patient. The father was diagnosed in adulthood and had nonobstructive HCM, whereas the child had obstructive HCM.

Group II (Channelopathies)

Of the five patients in this group, four were suspected to have long QT syndrome (LQTS). Two of them were found to have gene variants confirming LQTS. Patient 9, whose sibling suffered a sudden cardiac death (SCD), was found to have a missense variation in the KCNE1 gene inherited from the mother, suggestive of LQTS 5. Patient 10, who presented with recurrent syncope, was detected to have a heterozygous missense variation in the KCNQ1 gene, suggestive of LQTS type 1. One patient (Patient 13) had catecholaminergic polymorphic ventricular tachycardia (CPVT). He presented with a history of exertional syncope. His brother had SCD at the age of 21 years while sprinting to board a bus. A detailed pedigree chart showed that three of his maternal aunts and two maternal uncles had succumbed in their second or third decade of life, during some form of exercise such as running and dancing. Although his resting electrocardiogram was normal, he developed multiple ventricular ectopics on exercise stress test. Hence, a clinical diagnosis of CPVT was made and he was prophylactically treated with an implantable cardioverter-defibrillator (ICD). Later when he was enrolled in the cardiogenetic clinic, his genetic analysis confirmed the clinical diagnosis by revealing a heterozygous missense variation in the RYR2 gene, also identified in his asymptomatic mother.

Group III (Miscellaneous)

Patient 14 presented with cyanosis due to elevated methemoglobin levels. The genetic test confirmed the diagnosis of autosomal recessive methemoglobinemia Type I and the gene variant was found in heterozygous states in both parents and paternal grandmother.

 Post-Test Counseling

In the DCM group, the patients with pathogenic variants were counseled about the confirmation of etiology, continuation of medications, and screening of other family members. As they planned to have future pregnancies, parents of the patient with autosomal recessive NEXN mutation (Patient 2) were counseled about the risk involved and need for antenatal testing. The families of patients with VUS were counseled about probable etiology and future implications. The family with ventricular noncompaction who did not have any pathogenic variant on genetic testing was advised to remain on follow-up as there was echocardiographic evidence of a familial disorder. It is well known that phenotype-positive genotype-negative cases exist in the inherited cardiac disease spectrum and that treatment decisions should not solely rely on genetic test results but should be based on comprehensive clinical assessment.

In Group II, the families with pathogenic mutations were advised continuation of medications and screening of other family members. The two patients without an underlying mutation were weaned off beta-blockers. The patient with CPVT was reluctant to undergo ICD battery replacement, as there were no documented shocks for 10 years. Confirmation of CPVT on genetic testing re-emphasized the requirement of ICD as there was a risk of SCD.

Thus, genetic testing had diagnostic, prognostic, and therapeutic implications in our cohort.

 Clinical Implications of Cardiogenetic Clinics

The recent advances in the field of genomic medicine have unraveled the heritable nature of several cardiac diseases. In LQTS, genetic testing not only confirms the diagnosis but also guides the pharmacological management. While beta-blockers are the first line of treatment in LQTS, mexiletine is the drug of choice for LQTS 3. Genetic testing helps identify carriers of disease, who could be offered targeted therapy to modify disease onset or progression. For example, MYBPC3 mutation carriers of HCM were found to be more responsive to disease-modifying treatment with diltiazem than MYH7 mutation carriers, in a double-blind trial.[3] The genotype-positive/phenotype-negative carriers with a family history of DCM can be followed up regularly and monitored with echocardiographic global longitudinal strain for early evidence of ventricular function impairment.

Establishment of cardiogenetic clinics in tertiary care centers can help in systematic evaluation of inherited cardiac diseases, paving the way for appropriate diagnosis and management of the index patient as well as cascade screening of asymptomatic family members.

Financial support and sponsorship

This study received funding from MedGenome Labs Ltd, Bengaluru, India.

Conflicts of interest

There are no conflicts of interest.


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