Launched in November 2020, the NHCS Cardiogenetics Clinic provides care for patients and their families who have been diagnosed, or are suspected to have, an inherited cardiac condition. Since its inception, the clinic has since evolved into a dedicated service that offers precise clinical diagnosis aiding doctors and patients in decision making for early intervention and care management.

Established under the stewardship of the SingHealth Duke-NUS Genomic Medicine Centre (SDGMC), the Cardiovascular Genetics (CVG) service is a dedicated specialty genetic service at NHCS to help patients with genetic disorders or conditions with a suspected genetic basis. Since its inception, the service has grown and is currently led by Dr Iswaree Devi Balakrishnan, Consultant, Department of Cardiology, NHCS and supported by Dr Nikki Fong, Consultant, Genetics Service, KK Women’s and Children’s Hospital (KKH), as well as Ms Yasmin Bylstra, Senior Principal Genetic Counsellor and Ms Nellie Chai, Genetic Counsellor Associate.

The CVG service sees the following types of patients:

Over the last three years, this hub-and-spoke initiative supported by the SDGMC, has seen an increase in patient referrals for genetic testing annually, with the most common reasons for referrals including suspected genetic cardiomyopathies like dilated or hypertrophic cardiomyopathy, as well as familial or syndromic aortopathies such as Marfan and Ehler-Danlos syndromes. 

The CVG service is offered at inpatient and outpatient settings. A patient suspected to have an inherited cardiac condition based on clinical history and/or initial cardiac investigations, will be referred to CVG service for further assessment. Patients will receive pre-test counselling, interpretation of the genetic test and follow-up, including screening of close and extended family, as part of the early diagnosis plan. 

Recognising the emotional burden that patients may face at being a receiving carrier’s diagnosis, the CVG service team, comprising doctors, nurses and genetic counsellors, will also guide patients on communicating the genetic risk information with their at-risk relatives and address their concerns. 

Predictive genetic testing or cascade testing may be offered to the at-risk family members, if necessary.  

“Genetic testing at the clinical setting facilitates the need for cascade testing for at-risk family members - allowing early detection of similar genetic mutation in the asymptomatic family members, and conversely, can offer a sense of relief, in the absence of the mutation,” shared Dr Balakrishnan.

Indeed, the identification of an underlying genetics basis for many cardiovascular conditions has evolved in the past decade and recognised to have significant implications for patient management. Dr Fong shared that genetic testing could help in establishing a definitive, etiologically based diagnosis, with many cardiology practice guidelines incorporating genetic data in the recommendations for diagnosis and clinical management. 

“Genetic testing in cardiovascular disease can potentially effect changes at the community and quaternary care levels. Knowing one’s risk and health condition early allows patients and their family to take preventive actions such as medications and regular follow-ups with his doctor, as well as start adopting a healthier lifestyle and diet at home,” said Prof Yeo Khung Keong, Chief Executive Officer, NHCS.

A previously healthy 32-year-old man, Alex (identified as 3B in the genogram in Figure 1) collapsed while running on a treadmill. Unfortunately, he did not survive despite cardiopulmonary resuscitation (CPR). To understand the cause of his sudden cardiac death (SCD), a post-mortem analysis, including genetic testing was conducted. The results revealed Alex had a rare genetic heart condition called arrhythmogenic left ventricular cardiomyopathy (ALVC), marked by extensive scarring and fibrofatty infiltration of the left ventricle (the heart's pumping chamber). His post-mortem genetic test found a pathogenic variant (mutation) in the FLNC gene, associated with ALVC.

FLNC gene related ALVC is a rare heart condition associated with lethal arrythmias (heart rhythm), sudden cardiac death (SCD) and, less commonly, heart failure. It is passed down through families in an autosomal dominant manner, meaning there's a 50% chance of passing the gene to a first degree relative (i.e., immediate family member).

Alex's family was seen at NHCS’ CVG clinic for a comprehensive assessment to understand their risk of inheriting the genetic mutation. Before the visit, family members had undergone tests several tests including electrocardiogram (ECG) and echocardiogram (ultrasound scan of the heart) that revealed normal results. 

At the CVG clinic, a genogram, a visual representation of a family tree, was constructed (Figure 1). This tool incorporates family health history, aiding in understanding inheritance patterns and facilitates communication about potential genetic risks amongst family members.

Given that ALVC can be present in families without obvious symptoms, and even with normal cardiac testing, we counselled and recommended genetic testing for the specific FLNC mutation (linked to ALVC) in Alex's immediate family, and they were agreeable. 

The genetic testing results revealed that Alex's father (2C) and brother (3C) had the mutation, while his mother (2D) and sisters (3A and 3D) did not. This information guided the family's future healthcare management. A surveillance plan comprising regular monitoring of the heart health and preventive measures of family members having the genetic mutation and who are at risk of developing ALVC and associated complications was developed. Family members without the genetic mutation were released from cardiac surveillance.

Understanding the genetic risk is also crucial for future family planning, especially for Alex’s younger brother (3C), who may consider having more children. The genetic test also unveiled potential risks for Alex’s son (4A), Alex's brother's children (4B and 4C) and the father's siblings (2A and 2B). Given that the children are young and ALVC is less likely to manifest in childhood, a consensus was reached to defer testing until a later age.

Dr Balakrishan shared that this case study demonstrates the utility of genetic testing and how NHCS’ CVG service holistically integrates genetic testing into clinical care for managing inherited cardiac conditions. Through a comprehensive CVG assessment, tailored healthcare plans were devised based on genetic results, ensuring vigilant monitoring for carriers and relieving others from unnecessary heart check-ups.  This underscores the pivotal role of CVG service in the personalised management of inherited cardiac conditions.

REFER A PATIENT

If you have a patient with a suspected inherited cardiovascular disease, you may refer them to the NHCS CVG service by the following contacts:

Tel: 6704 2000

Fax: 6222 9258

Email: central.appt@nhcs.com.sg

The types of conditions that are seen in the clinic include: