FLNC Associated Restrictive Cardiomyopathy and Hypertrabeculation, a Rare Association

Area of Science:

• Cardiology
• Genetics
• Molecular Biology

Background:

• Restrictive cardiomyopathy and hypertrabeculation are severe cardiac conditions.
• Early-onset genetic factors are increasingly recognized in pediatric cardiomyopathies.
• Whole exome sequencing is a powerful tool for identifying novel genetic variants.

Observation:

• A six-year-old girl presented with early-onset restrictive cardiomyopathy and hypertrabeculation.
• Whole exome sequencing identified a novel heterozygous missense variant in the FLNC gene.
• The same FLNC variant was present in her father, who was asymptomatic with normal cardiac imaging.

Findings:

• The identified FLNC gene variant is novel and has not been previously reported.
• The variant is classified as likely pathogenic based on its novelty and clinical presentation.
• The father's asymptomatic status despite carrying the variant suggests incomplete penetrance or variable expressivity.

Implications:

• This discovery expands the known genetic landscape of FLNC-associated cardiomyopathies.
• Understanding variable expressivity is crucial for genetic counseling and predicting disease course.
• Further research into FLNC variants can improve diagnosis and therapeutic strategies for inherited heart diseases.