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The Expanding Spectrum of FLNC Cardiomyopathy

Emanuele Monda
Martina Caiazza
1 and
Giuseppe Limongelli
Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy
Institute of Cardiovascular Sciences, University College of London and St. Bartholomew’s Hospital, London WC1E 6DD, UK
Author to whom correspondence should be addressed.
Cardiogenetics 2022, 12(4), 276-277;
Submission received: 16 November 2022 / Accepted: 18 November 2022 / Published: 22 November 2022
Mutations in gene encoding filamin C (FLNC) have been historically associated with hypertrophic cardiomyopathy (HCM) and myofibrillar myopathy [1]. Subsequently, several variants have been associated with other cardiomyopathy phenotype, including dilated cardiomyopathy (DCM) and arrhythmogenic left ventricular cardiomyopathy (ALVC) [2]. In particular, FLNC variants have been associated with a peculiar left ventricular phenotype, with diffuse non-ischemic fibrosis, and ventricular arrhythmias potentially leading to sudden cardiac death [3].
Recently, FLNC variants have been found in patients with restrictive cardiomyopathy (RCM) [4].
The contribution of a genetic pathogenesis to RCM has not been completely elucidated. Moreover, the knowledge about relevant mutations and genes implicated in this condition is limited due to the rarity of the disease, in particular in pediatric patients.
Girolami et al. described a case of a 7-year-old girl diagnosed with RCM after a comprehensive clinical evaluation. In particular, the patient showed a negative family history for sudden cardiac death and cardiomyopathies, no extra-cardiac manifestations, electrocardiogram and echocardiography revealing bi-atral enlargement. In addition, due to increased pulmonary vascular resistance at cardiac catheterization, the patient had been evaluated for heart transplantation.
The patient underwent clinical exome, which evidenced a de novo variant c.6527_6547dup (p.Arg2176_2182dup) in the FLNC, classified as likely pathogenic according to the American College of Medical Genetics [5].
Currently, it is not completely understood why different FLNC mutations are responsible for different clinical entities. It has been observed that missense mutation leads to HCM, while truncating mutation to DCM or ALVC [2]. Occasionally, missense mutations in FLNC have recently shown co-segregation with RCM in two Caucasian families [6].
FLNC encodes for the protein filamin C, which is localized at the level of the Z-bands and the intercalated disc. It is known to be involved in the sarcomeric organization and in the intercellular adhesion [7,8]. The identification of FLNC variants has significant implication for management strategies since they have been associated with increased sudden cardiac death risk and poor outcome [2].
This case report highlights the importance of performing exome sequencing to identify rare genetic variants, in order to guide therapy and offer genetic counselling to the family.

Author Contributions

E.M., M.C. and G.L. drafted and critically revised the manuscript. All authors have read and agreed to the published version of the manuscript.


This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.


  1. Geisterfer-Lowrance, A.A.; Kass, S.; Tanigawa, G.; Vosberg, H.P.; McKenna, W.; Seidman, C.E.; Seidman, J.G. A molecular basis for familial hypertrophic cardiomyopathy: A beta cardiac myosin heavy chain gene missense mutation. Cell 1990, 62, 999–1006. [Google Scholar] [CrossRef]
  2. Celeghin, R.; Cipriani, A.; Bariani, R.; Bueno Marinas, M.; Cason, M.; Bevilacqua, M.; De Gaspari, M.; Rizzo, S.; Rigato, I.; Da Pozzo, S.; et al. Filamin-C variant-associated cardiomyopathy: A pooled analysis of individual patient data to evaluate the clinical profile and risk of sudden cardiac death. Heart Rhythm. 2022, 19, 235–243. [Google Scholar] [CrossRef]
  3. Ortiz-Genga, M.F.; Cuenca, S.; Dal Ferro, M.; Zorio, E.; Salgado-Aranda, R.; Climent, V.; Padrón-Barthe, L.; Duro-Aguado, I.; Jiménez-Jáimez, J.; Hidalgo-Olivares, V.M.; et al. Truncating FLNC Mutations Are Associated with High-Risk Dilated and Arrhythmogenic Cardiomyopathies. J. Am. Coll. Cardiol. 2016, 68, 2440–2451. [Google Scholar] [CrossRef] [PubMed]
  4. Ader, F.; De Groote, P.; Réant, P.; Rooryck-Thambo, C.; Dupin-Deguine, D.; Rambaud, C.; Khraiche, D.; Perret, C.; Pruny, J.F.; Mathieu-Dramard, M.; et al. FLNC pathogenic variants in patients with cardiomyopathies: Prevalence and genotype-phenotype correlations. Clin. Genet. 2019, 96, 317–329. [Google Scholar] [CrossRef]
  5. Richards, S.; Aziz, N.; Bale, S.; Bick, D.; Das, S.; Gastier-Foster, J.; Grody, W.W.; Hegde, M.; Lyon, E.; Spector, E.; et al. ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015, 17, 405–424. [Google Scholar] [CrossRef] [Green Version]
  6. Brodehl, A.; Ferrier, R.A.; Hamilton, S.J.; Greenway, S.C.; Brundler, M.A.; Yu, W.; Gibson, W.T.; McKinnon, M.L.; McGillivray, B.; Alvarez, N.; et al. Mutations in FLNC are Associated with Familial Restrictive Cardiomyopathy. Hum Mutat. 2016, 37, 269–279. [Google Scholar] [CrossRef] [PubMed]
  7. Razinia, Z.; Mäkelä, T.; Ylänne, J.; Calderwood, D.A. Filamins in mechanosensing and signaling. Annu. Rev. Biophys. 2012, 41, 227. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  8. González-Morales, N.; Holenka, T.K.; Schöck, F. Filamin actin-binding and titin-binding fulfill distinct functions in Z-disc cohesion. PLoS Genet. 2017, 13, e1006880. [Google Scholar] [CrossRef] [PubMed]
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Monda, E.; Caiazza, M.; Limongelli, G. The Expanding Spectrum of FLNC Cardiomyopathy. Cardiogenetics 2022, 12, 276-277.

AMA Style

Monda E, Caiazza M, Limongelli G. The Expanding Spectrum of FLNC Cardiomyopathy. Cardiogenetics. 2022; 12(4):276-277.

Chicago/Turabian Style

Monda, Emanuele, Martina Caiazza, and Giuseppe Limongelli. 2022. "The Expanding Spectrum of FLNC Cardiomyopathy" Cardiogenetics 12, no. 4: 276-277.

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