Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome
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...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
BMC
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/d0fc9cf40c2a4de0a8134ace8ab5266e |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:d0fc9cf40c2a4de0a8134ace8ab5266e |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:d0fc9cf40c2a4de0a8134ace8ab5266e2021-12-05T12:17:00ZCardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome10.1186/s13023-021-02128-11750-1172https://doaj.org/article/d0fc9cf40c2a4de0a8134ace8ab5266e2021-12-01T00:00:00Zhttps://doi.org/10.1186/s13023-021-02128-1https://doaj.org/toc/1750-1172Abstract 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.Clarisse BillonSalma AdhamNatalia Hernandez PobleteAnne LegrandMichael FrankLaurent ChicheStephane ZuilyKarelle BenistanLaurent SavaleKhaoula Zaafrane-KhachnaouiAnne-Claire BrehinLaurence BalTiffany BusaMélanie FradinChloé QuelinBertrand ChesneauDenis WahlPatricia FergelotCyril GoizetTristan MiraultXavier JeunemaitreJuliette AlbuissonBordeaux-cohort collaboratorsBMCarticleFLNAConnective tissue disorderAortic aneurysm and dissectionCardiovascular anomaliesEhlers–DanlosMedicineRENOrphanet Journal of Rare Diseases, Vol 16, Iss 1, Pp 1-13 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
FLNA Connective tissue disorder Aortic aneurysm and dissection Cardiovascular anomalies Ehlers–Danlos Medicine R |
| spellingShingle |
FLNA Connective tissue disorder Aortic aneurysm and dissection Cardiovascular anomalies Ehlers–Danlos Medicine R 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 Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Clarisse Billon |
| title |
Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome |
| title_short |
Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome |
| title_full |
Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome |
| title_fullStr |
Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome |
| title_full_unstemmed |
Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome |
| title_sort |
cardiovascular and connective tissue disorder features in flna-related pvnh patients: progress towards a refined delineation of this syndrome |
| publisher |
BMC |
| publishDate |
2021 |
| url |
https://doaj.org/article/d0fc9cf40c2a4de0a8134ace8ab5266e |
| work_keys_str_mv |
AT clarissebillon cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT salmaadham cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT nataliahernandezpoblete cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT annelegrand cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT michaelfrank cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT laurentchiche cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT stephanezuily cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT karellebenistan cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT laurentsavale cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT khaoulazaafranekhachnaoui cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT anneclairebrehin cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT laurencebal cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT tiffanybusa cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT melaniefradin cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT chloequelin cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT bertrandchesneau cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT deniswahl cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT patriciafergelot cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT cyrilgoizet cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT tristanmirault cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT xavierjeunemaitre cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT juliettealbuisson cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome AT bordeauxcohortcollaborators cardiovascularandconnectivetissuedisorderfeaturesinflnarelatedpvnhpatientsprogresstowardsarefineddelineationofthissyndrome |
| _version_ |
1718372104790867968 |