Dilated cardiomyopathy: the role of genetics, highlighted in a family with Filamin C (FLNC) variant

Abstract

Dilated cardiomyopathy (DCM) is a heterogenous group of disorders characterised by left ventricular dilatation and dysfunction, in the absence of factors affecting loading conditions such as hypertension or valvular disease, or significant coronary artery disease. The prevalence of idiopathic DCM is estimated between 1:250 and 1:500 individuals. Determining the aetiology of DCM can be challenging, particularly when evaluating an individual and index case with no classical history or investigations pointing towards an obvious acquired cause, or no clinical clues in the family history to suggest a genetic cause. We present a family affected by DCM associated with Filamin C variant, causing sudden cardiac death at a young age and heart failure due to severe left ventricular impairment and myocardial scarring. We review the diagnosis and treatment of DCM, its genetic associations and potential acquired causes. Thorough assessment is mandatory to risk stratify and identify patients who may benefit from primary prevention implantable cardioverter defibrillator therapy according to international guidelines. Genetic testing has some limitations, and is positive in only 20%–35% of DCM, but should be considered in specific cases to identify families who may benefit from cascade screening after appropriate counselling. The management of often complex familial cardiomyopathy requires specialist input for every case, and the appropriate infrastructure to coordinate investigations.

Biallelic truncating variants in children with titinopathy represent a recognizable condition with distinctive muscular and cardiac characteristics: a report on five patients

“…It is well known that TTNtv are associated with increased arrhythmic events, independent of conventional risk factors. However, our data show a low rate of arrhythmogenic events compared with other forms of DCM probably due to the young age of our patient cohort (26)(27)(28)(29)(30)(31).…”

Genetic characterization of dilated cardiomyopathy patients undergoing heart transplantation in the Chinese population by whole-exome sequencing

“…FLNC variants have been shown to play a vital role in the pathogenesis of cardiomyopathies [ 27 , 28 ]. Nontruncated FLNC tends to result in hypertrophic cardiomyopathy and restrictive cardiomyopathy, and truncated FLNC tends to result in DCM and arrhythmogenic right ventricular cardiomyopathy [ 29 , 30 ]. In our cohort, 8.7% (18/208) of patients carried FLNC truncating variants, and this frequency was much higher than that in European and North American DCM cohorts (1%) [ 7 ].…”

State of the art: multimodality imaging in dilated cardiomyopathy

“…Ring-like patterns of LGE, often in a subepicardial distribution, are most frequently seen in patients with causative variants in desmoplakin ( DSP ) and filamin C ( FLNC) ( figure 6A). 13 14 These genotypes are also more commonly associated with regional differences in LV wall motion. An overlap between arrhythmogenic ventricular cardiomyopathy (AVC) and DCM is increasingly recognised.…”