You are here

Article Text

Article menu
Download PDFPDF
Phenotypes
Original research
Arterial aneurysm and dissection: toward the evolving phenotype of Tatton-Brown-Rahman syndrome
  1. Vicken Totten1,2,
  2. Gisela Teixido-Tura3,4,
  3. Fermina Lopez-Grondona5,
  4. Paula Fernandez-Alvarez6,7,
  5. Amaia Lasa-Aranzasti6,7,
  6. Patricia Muñoz-Cabello6,7,
  7. Rika Kosaki8,
  8. Eduardo F Tizzano6,7,
  9. Wendy Dewals9,
  10. Emma Borràs10,
  11. Elena Gonzalez Cañas11,
  12. Berta Almoguera5,12,
  13. Bart Loeys13,
  14. Irene Valenzuena6,7
  1. 1 Kaweah Health System, Visalia, California, USA
  2. 2 Kayenta Health Center of the Indian Health Service, Kayenta, Arizona, USA
  3. 3 Department of Cardiology, Hospital Universitari Vall d'Hebron, CIBER-CV, Vall d'Hebron institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain
  4. 4 Department of Genetics and Genomics, Hospital Universitario Fundacion Jimenez Diaz (IIS-FJD), Madrid, Spain
  5. 5 European Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD Rare Disease Working Group, Barcelona, Spain
  6. 6 Department of Clinical and Molecular Genetics, Vall d'Hebron University Hospital. Medicine Genetics Group, Vall d'Hebron Research Institute, Barcelona, Spain
  7. 7 European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA), Barcelona, Spain
  8. 8 Division of Medical Genetics, National Center for Child Health and Development, Tokyo, Japan
  9. 9 Pediatric Cardiology Department, Antwerp University Hospital, Edegem, Belgium
  10. 10 Molecular Genetics Unit, Consorci Sanitari de Terrassa, Terrassa, Spain
  11. 11 Angiology and Vascular Surgery, Hospital Universitari Parc Tauli, Sabadell, Spain
  12. 12 Centro de Investigacion Biomedica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain
  13. 13 Center for Medical Genetics, Antwerp University Hospital/University of Antwerp, Antwerp, Belgium
  1. Correspondence to Dr Irene Valenzuena, Department of Clinical and Molecular Genetics, Hospital Vall d'Hebron, Barcelona, 08035, Spain; irene.valenzuela{at}vallhebron.cat

Abstract

Background Tatton-Brown-Rahman syndrome (TBRS) is a rare disorder, caused by DNMT3A heterozygous pathogenic variants, and first described in 2014. TBRS is characterised by overgrowth, intellectual disability, facial dysmorphism, hypotonia and musculoskeletal features, as well as neurological and psychiatric features. Cardiac manifestations have also been reported, mainly congenital malformations such as atrial septal defect, ventricular septal defect and cardiac valvular disease. Aortic dilatation has rarely been described.

Methods Here we have undertaken a detailed clinical and molecular description of eight previously unreported individuals, who had TBRS and arterial dilatation and/or dissection, mainly thoracic aortic aneurysm (TAA). We have also reviewed the seven previously published cases of TAA in individuals with TBRS to try to better delineate the vascular phenotype and to determine specific follow-up for this condition.

Results We include eight new patients with TBRS who presented with arterial aneurysms mainly involving aorta. Three of these patients presented with dissection that required critical surgery.

Conclusions Arterial aneurysms and dissections are a potentially lethal, age-dependent manifestation. The prevalence of aortic disease in individuals with TBRS is far in excess of that expected in the general population. This cohort, together with individuals previously published, illustrates the importance to consider dilatation/dissection, mainly in aorta but also in other arteries. Arterial vascular weakness may therefore also be a cardinal feature of TBRS and vascular surveillance is recommended.

  • Aneurysm
  • Cardiovascular Diseases
  • Exome Sequencing

Data availability statement

Data are available upon reasonable request.

https://doi.org/10.1136/jmg-2024-109861

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Data availability statement

    Data are available upon reasonable request.

    View Full Text

    Footnotes

    • Contributors Conceptualisation—VYT, EFT and IV. Data curation—VYT, GT-T, FL-G, PF-A, AL-A, PM-C, RK, WD, EB, EGC, BA, BL, EFT and IV. Formal analysis—VYT, EFT and IV. Writing (original draft)—VYT, EFT and IV. Writing (review and editing)—all authors. Guarantor—IV.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.