Infanticide vs. inherited cardiac arrhythmias

Area of Science:

• Genetics
• Molecular Biology
• Cardiology

Background:

• A mother was convicted of killing her four children who died suddenly between 19 days and 18 months of age.
• In 2019, a genetic investigation was requested to determine if a natural cause could explain the children's deaths.

Purpose of the Study:

• To investigate a potential genetic cause for the sudden, unexplained deaths of four children.
• To analyze a novel calmodulin variant for its functional impact on cardiac function.

Main Methods:

• Whole genome or exome sequencing of the mother and her four children.
• Functional analysis of a novel CALM2 variant, including calcium-binding affinity and effects on calcium channels (CaV1.2 and RyR2).

Main Results:

• Two children carried a novel maternal calmodulin variant (CALM2 G114R).
• This variant impairs calmodulin's ability to bind calcium and regulate key cardiac calcium channels.
• The functional effects of CALM2 G114R are similar to other known arrhythmogenic variants.

Conclusions:

• A novel calmodulinopathy (CALM2 G114R) is a plausible natural explanation for the deaths of two children.
• This genetic variant may lead to fatal arrhythmic events, potentially triggered by infections.
• The findings suggest a genetic basis for sudden cardiac death in these cases.