Variable clinical expression of a novel FLNC truncating variant in a large family.
Int J Cardiol
; 401: 131849, 2024 Apr 15.
Article
in En
| MEDLINE
| ID: mdl-38360096
ABSTRACT
BACKGROUND:
Variants in Filamin-C (FLNC) have been associated with various hereditary cardiomyopathies. Recent literature reports a prevalence of sudden cardiac death (SCD) of 13-25% among carriers of truncating-variants, with mean age of 42±15 years for first SCD event. This study reports two familial cases of SCD and the results of cascade screening of their large family.METHODS:
Molecular-autopsy of the SCD victims revealed a novel truncating-variant in the FLNC gene (chr 7128496880 [hg19]; NM_001458.5; c.7467_7474del; p.(Ser2490fs)). We screened thirty-two family members following genetic counseling, and variant carriers underwent a comprehensive workup followed by consultation with a cardiologist with expertise in the genetics of cardiac diseases.RESULTS:
Seventeen variant carriers were identified ages between 9 and 85 (mean 47±26). Fifteen underwent clinical evaluation. To date, none of the identified carriers has had major adverse events. In evaluated patients, ECG showed right-axis deviation in 60% (n = 9). Holter recorded frequent premature ventricular contractions (PVCs) (991±2030 per 24 h) in 33% (n = 5) with 4 patients having polymorphic PVC morphology. Three carriers had echocardiographic evidence of mild left-ventricular (LV) systolic dysfunction and another with mild LV dilatation. Cardiac magnetic-resonance (CMR) exhibited lategadolinium-enhancement in 10 out of 11 exams, mainly in the mid-myocardium and sub-epicardium, frequently involving the septum and the inferior-lateral wall.CONCLUSION:
This large FLNC truncating variant carrier family exhibits high cardiomyopathy penetrance, best diagnosed by CMR, with variable clinical expressions. These findings present a challenge in SCD prevention management and underscoring the imperative for better risk stratification measures.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ventricular Premature Complexes
/
Cardiomyopathies
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Child
/
Humans
/
Middle aged
Language:
En
Journal:
Int J Cardiol
Year:
2024
Document type:
Article
Country of publication: