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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2021

Open Access 01-12-2021 | Aortic Aneurysm | Research

Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome

Authors: Clarisse Billon, Salma Adham, Natalia Hernandez Poblete, Anne Legrand, Michael Frank, Laurent Chiche, Stephane Zuily, Karelle Benistan, Laurent Savale, Khaoula Zaafrane-Khachnaoui, Anne-Claire Brehin, Laurence Bal, Tiffany Busa, Mélanie Fradin, Chloé Quelin, Bertrand Chesneau, Denis Wahl, Patricia Fergelot, Cyril Goizet, Tristan Mirault, Xavier Jeunemaitre, Juliette Albuisson, Bordeaux-cohort collaborators

Published in: Orphanet Journal of Rare Diseases | Issue 1/2021

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Abstract

Background

FLNA Loss-of-Function (LoF) causes periventricular nodular heterotopia type 1 (PVNH1), an acknowledged cause of seizures of various types. Neurological symptoms are inconstant, and cardiovascular (CV) defects or connective tissue disorders (CTD) have regularly been associated. We aimed at refining the description of CV and CTD features in patients with FLNA LoF and depicting the multisystemic nature of this condition.

Methods

We retrospectively evaluated FLNA variants and clinical presentations in FLNA LoF patient with at least one CV or CTD feature, from three cohorts: ten patients from the French Reference Center for Rare Vascular Diseases, 23 patients from the national reference diagnostic lab for filaminopathies-A, and 59 patients from literature review.

Results

Half of patients did not present neurological symptoms. Most patients presented a syndromic association combining CV and CTD features. CV anomalies, mostly aortic aneurysm and/or dilation were present in 75% of patients. CTD features were present in 75%. Variants analysis demonstrated an enrichment of coding variants in the CH1 domain of FLNA protein.

Conclusion

In FLNA LoF patients, the absence of seizures should not be overlooked. When considering a diagnosis of PVNH1, the assessment for CV and CTD anomalies is of major interest as they represent interlinked features. We recommend systematic study of FLNA within CTD genes panels, regardless of the presence of neurological symptoms.
Appendix
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Metadata
Title
Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome
Authors
Clarisse Billon
Salma Adham
Natalia Hernandez Poblete
Anne Legrand
Michael Frank
Laurent Chiche
Stephane Zuily
Karelle Benistan
Laurent Savale
Khaoula Zaafrane-Khachnaoui
Anne-Claire Brehin
Laurence Bal
Tiffany Busa
Mélanie Fradin
Chloé Quelin
Bertrand Chesneau
Denis Wahl
Patricia Fergelot
Cyril Goizet
Tristan Mirault
Xavier Jeunemaitre
Juliette Albuisson
Bordeaux-cohort collaborators
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2021
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-021-02128-1

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