Understanding the Genetic and Molecular Basis of Inherited Cardiac Conditions (ICCs) and SADS

By Poppy’s Mum

Last week, I wrote about Sudden Arrhythmic Death Syndrome (SADS) what it is, how it strikes unexpectedly, and why so many families never see it coming. But what I’ve learned through losing my daughter, Poppy, is that SADS is not a disease itself, but the sudden, tragic outcome of an underlying Inherited Cardiac Condition (ICC).

Poppy passed away in 2024 due to undiagnosed Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), one of these ICCs. ICCs are genetic disorders of the heart’s electrical system that can remain invisible until SADS occurs. Understanding the genetics behind ICCs is crucial, not just for awareness, but for protecting other children and families who may carry the same silent risk.

1. How ICCs Became Part of My Grief

Before losing Poppy, I didn’t know what ICCs were. I didn’t understand that a tiny change in DNA could make a heart vulnerable to arrhythmias, invisible on scans, and yet lethal in certain circumstances.

SADS was the first I knew of the danger. Later, I learned that SADS is the event caused by the invisible ICC hiding in Poppy’s heart. That distinction matters, because while SADS is sudden and heartbreaking, ICCs are what can be identified, studied, and sometimes screened for in living family members.

2. Genes Behind ICCs

Through our journey, I had to learn about the genes most commonly associated with ICCs, the ones that can lead to SADS if left undetected:

SCN5A

Controls sodium channels in heart cells. Variants are linked to several ICCs and can predispose someone to life-threatening arrhythmias.

KCNQ1

Regulates potassium flow. Variants cause Long QT Syndrome, an ICC that can lead to SADS, often triggered by exercise or stress.

RYR2

Central to CPVT, the ICC that took Poppy. RYR2 affects calcium release in heart cells during adrenaline surges, explaining why seemingly normal activity can trigger dangerous rhythms.

Learning about these genes was overwhelming at first, but they became the key to understanding why SADS can occur and how ICCs silently affect healthy-looking hearts.

3. Understanding ICCs and Genetic Conditions

An Inherited Cardiac Condition is a genetic alteration that disrupts the heart’s electrical system. ICCs can:

• Be inherited from a parent or appear de novo

• Remain silent for years

• Present as SADS when triggered by stress, exercise, or other factors

Recognising ICCs as the underlying cause of SADS is empowering, it means families can be screened, monitored, and sometimes protected, even after tragedy.

4. Genetic and Genomic Testing in ICCs

Genetic testing examines known ICC genes, including SCN5A, KCNQ1, and RYR2.

Genomic testing looks more broadly when the ICC is not obvious.

Both help identify living family members who may carry the same genetic risk and prevent future SADS events. For us, this knowledge was the only way to protect Poppy’s siblings and extended family.

5. Post-Mortem DNA and Molecular Autopsy

After Poppy’s death, specialists collected post-mortem DNA to perform a molecular autopsy taking a small sample of spleen. This testing searches for ICCs that can cause SADS when the heart appears normal.

Spleen Sampling as part of the molecular autopsy:

• Identified CPVT as the cause of SADS

• Enabled family screening

• Provided clarity in the darkest moments

It didn’t bring Poppy back, but it allowed her story to protect others.

6. Familial CPVT: The Invisible Risk

CPVT, like many ICCs, is difficult to detect:

• ECGs often appear normal

• The heart looks normal on scans

• Symptoms appear only during adrenaline surges

• Fainting may be misinterpreted

For families, this means that SADS may be the first visible warning sign of an underlying ICC. Understanding ICCs can save lives through screening and early intervention.

7. Why I Share This

Writing about ICCs and SADS is painful, but I do it because knowledge can protect other families.

If our experience encourages even one family to:

• Ask about ICCs

• Pursue genetic or genomic testing

• Request spleen sampling after unexplained death

• Take fainting or collapse seriously

…then Poppy’s story continues to save lives.

Poppy didn’t get the lifetime she deserved, but awareness of ICCs and SADS can protect other children and young adults, and that is her legacy.

If you would like to support Poppy’s Light Foundation, please get in touch via email at info@poppyslightfoundation.com. Alternatively, donations mean the world to us too.