Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome
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Published:2021-12
Issue:1
Volume:16
Page:
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ISSN:1750-1172
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Container-title:Orphanet Journal of Rare Diseases
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language:en
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Short-container-title:Orphanet J Rare Dis
Author:
Billon ClarisseORCID, Adham Salma, Hernandez Poblete Natalia, Legrand Anne, Frank Michael, Chiche Laurent, Zuily Stephane, Benistan Karelle, Savale Laurent, Zaafrane-Khachnaoui Khaoula, Brehin Anne-Claire, Bal Laurence, Busa Tiffany, Fradin Mélanie, Quelin Chloé, Chesneau Bertrand, Wahl Denis, Fergelot Patricia, Goizet Cyril, Mirault Tristan, Jeunemaitre Xavier, Albuisson Juliette, Dieux Anne, Labombarda Fabien, Rheims Sylvain, Boute Odile, Vincentelli André, Toutain Annick, Odent Sylvie, Lesca Gaetan, Vincent Marie, Piard Juliette, Favier Maud, Derambure Philippe, Edery Patrick, Thummler Susanne, Gérard Marion, Morice-Picard Fanny, Layet Valérie, Laroche Cécile, Pasquier Laurent, Sarrazin Elisabeth, Billette de Villemeur Thierry, Guyant-Marechal Lucie,
Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Genetics(clinical),General Medicine
Reference38 articles.
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