FLNC Missense Variants in Familial Noncompaction Cardiomyopathy

Jaap Van Waning,Paul Van Der Zwaag,Jan Jongbloed,Kadir Caliskan,Daphne Heijsman,Elke Hoendermis,Yvonne Hoedemaekers,Arthur Van Den Wijngaard,Albert Suurmeijer,Wouter Te Rijdt,Arne Jpma,Danielle Majoor-Krakauer,Marjon Van Slegtenhorst,Tineke Willems

doi:10.4081/cardiogenetics.2019.8181

Jaap Van Waning, Paul Van Der Zwaag + Show 12 more

Open Access

https://doi.org/10.4081/cardiogenetics.2019.8181

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Abstract

The majority of familial noncompaction cardiomyopathy (NCCM) is explained by pathogenic variants in the same sarcomeric genes that are associated with hypertrophic (HCM) and dilated (DCM) cardiomyopathy. Pathogenic variants in the filamin C gene (FLNC) have been linked to HCM and DCM. We expand the spectrum of FLNC related cardiomyopathies by presenting two families with likely pathogenic FLNC variants showing familial segregation of NCCM and concurrent coarctation of the aorta and/or mitral valve abnormalities.

Highlights

Introduction two relativesA niece (III:3), was diagnosed noncompaction from the apex to midvenwith noncompaction cardiomyopathy (NCCM) at age 21 and had surgery at tricular region with an NC/C ratio of 3.0Noncompaction cardiomyopathy age seven for coarctation of the aorta (Figure 2C and D)
Around 80% of these pathogenic variants involve the same sarcomere genes, that are the major causes for hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), in particular MYH7, MYBPC3 and TTN.[5,6]
Filamin C (FLNC) plays a central role in muscle functioning by maintaining the structural integrity of the muscle fibers

Summary

FLNC missense variants in familial noncompaction cardiomyopathy

Jaap I. van Waning,[1] Yvonne M. Hoedemaekers,[2] than 2 according to current echocardiographic criteria, or 2.3 on CMR.[1,2] Approximately 10% of patients diagnosed with NCCM have concurrent congenital heart defects (CHD).[3,4]. Majoor-Krakauer,[1] Paul A. van der Zwaag[2] fied. Around 80% of these pathogenic variants involve the same sarcomere genes, that are the major causes for hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), in particular MYH7, MYBPC3 and TTN.[5,6] Filamin C (FLNC) plays a central role in muscle functioning by maintaining the structural integrity of the muscle fibers. Pathogenic variants in FLNC were found to be associated with a wide spectrum of myopathies ranging from car-

Case Reports

Findings

Diagnostic DNA panel