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

Orphanet Journal of Rare Diseases

Bordeaux-cohort collaborators¹  Karelle Benistan²  Laurence Bal³  Tiffany Busa⁴  Patricia Fergelot⁵  Cyril Goizet⁵  Natalia Hernandez Poblete⁵  Michael Frank⁶  Xavier Jeunemaitre⁶  Clarisse Billon⁶  Salma Adham⁶  Anne Legrand⁶  Juliette Albuisson⁶  Tristan Mirault⁶  Laurent Chiche⁷  Anne-Claire Brehin⁸  Denis Wahl⁹  Stephane Zuily⁹  Chloé Quelin^1,10  Mélanie Fradin^1,10  Bertrand Chesneau^1,11  Khaoula Zaafrane-Khachnaoui^1,12  Laurent Savale^1,13 

[1] ;Centre de Référence des Syndromes d’Ehlers-Danlos non Vasculaires, Hôpital Raymond Poincaré, Assistance Publique Hôpitaux de Paris;Centre de référence régional Marfan et apparentés, Centre aortique, Hôpital La Timone, AP-HM;Département de Génétique Médicale, Hôpital La Timone, CHU de Marseille;Département de génétique médicale, Centre national de référence pour les maladies rares Neurogénétiques, Hôpital Pellegrin, CHU Bordeaux;Département de génétique, Centre national de référence pour les maladies vasculaires rares, centre de référence européen VASCERN MSA, Hôpital Européen Georges Pompidou, AP-HP;Faculté de médecine, Université de la Sorbonne;INSERM U1245 , Normandy center for Genomic and Personalized Medicine, Normandie Univ, CHU Rouen;Inserm UMRS 1116 DCAC, Université de Lorraine;Service de Génétique Clinique, Centre de Référence Maladies Rares CLAD-Ouest, ERN ITHACA, CHU Rennes, Hôpital Sud;Service de génétique médicale, Hôpital Purpan, CHU de Toulouse;Unité de génétique médicale 2, Hôpital L’Archet;Université Paris-Saclay;

关键词: FLNA;    Connective tissue disorder;    Aortic aneurysm and dissection;    Cardiovascular anomalies;    Ehlers–Danlos;   

DOI  :  10.1186/s13023-021-02128-1

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown