European Journal of Pediatrics

, Volume 173, Issue 3, pp 387–391 | Cite as

Loeys–Dietz syndrome in a Southeast Asian Hospital: a case series

  • Teck Wah Ting
  • Angeline Hwei Meeng Lai
  • Jonathan Tze Liang Choo
  • Teng Hong Tan
Original Article

Abstract

Loeys–Dietz syndrome (LDS) is a heritable connective tissue disease in which the activity of the transforming growth factor (TGF) beta signalling pathway is disrupted. The clinical features of LDS represent a clinical continuum that includes LDS type 1, with cutaneous, vascular, skeletal and craniofacial findings, and LDS type 2, with cutaneous, vascular and skeletal findings. We describe five Asian patients with genetically confirmed LDS with mutations in either the TGFBR1 or TGFBR2 gene. Their clinical features were similar to those reported in Caucasian patients. Two patients have novel mutations in TGFBR2. Transcatheter occlusion of patent ductus arteriosus (PDA) was safe and successful in three patients. Treatment with Losartan for aortic root dilatation was well tolerated in our patients, but the outcome is mixed. Among the three patients with follow-up data, aortic root dilatation has improved in two patients but continues to progress in the third patient despite treatment. Conclusion: We describe two novel mutations in TGFBR2 leading to LDS; PDA is common in our patients and can be safely occluded via transcatheter procedure.

Keywords

Loeys–Dietz syndrome Aortic root aneurysm Transforming growth factor beta Connective tissue disease 

Abbreviations

LDS

Loeys–Dietz syndrome

MFS

Marfan syndrome

PDA

Patent ductus arteriosus

TGF

Transforming growth factor

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Adès LC (2008) Evolution of the face in Loeys–Dietz syndrome type II: longitudinal observations from infancy in seven cases. Clin Dysmorphol 17(4):243–248PubMedCrossRefGoogle Scholar
  2. 2.
    Akutsu K, Morisaki H, Takeshita S, Sakamoto S, Tamori Y, Yoshimuta T, Yokoyama N, Nonoqi H, Ogino H, Morisaki T (2007) Phenotypic heterogeneity of Marfan-like connective tissue disorder with mutations in the transforming growth factor receptor genes. Circ J 71:1305–1309PubMedCrossRefGoogle Scholar
  3. 3.
    Kilic E, Alanay Y, Ütine E, Özgen-Mocan B, Robinson PN, Boduroğlu K (2012) Arterial tortuosity and aneurysm in a case of Loeys–Dietz syndrome type 1B with a mutation p.R537P in the TGFBR2 gene. Turk J Pediatr 54:198–202PubMedGoogle Scholar
  4. 4.
    Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak PJ, Cameron DE, De Backer J, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De Paepe AM, Dietz HC (2005) A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet 37:275–281PubMedCrossRefGoogle Scholar
  5. 5.
    Loeys BL, Dietz HC. ( 2008, revised 2013) Loeys-Dietz Syndrome. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2013.Google Scholar
  6. 6.
    Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, De Backer JF, Oswald GL, Symoens S, Manouvrier S, Roberts AE, Faravelli F, Greco MA, Pyeritz RE, Milewicz DM, Coucke PJ, Cameron DE, Braverman AC, Byers PH, De Paepe AM, Dietz HC (2006) Aneurysm syndromes caused by mutations in the TGF-β receptor. N Engl J Med 355:788–798PubMedCrossRefGoogle Scholar
  7. 7.
    Mátyás G, Arnold E, Carrel T, Baumgartner D, Boileau C, Berger W, Steinmann B (2006) Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders. Hum Mutat 27(8):760–769PubMedCrossRefGoogle Scholar
  8. 8.
    Togashi Y, Sakota H, Nishimura A, Matsumoto N, Hiraoka H, Matsuzawa Y (2007) A Japanese family of typical Loeys–Dietz syndrome with a TGFBR2 mutation. Intern Med 46:1995–2000PubMedCrossRefGoogle Scholar
  9. 9.
    Van de Laar IM, van der Linde D, Oei EH, Bos PK, Bessems JH, Bierma-Zeinstra SM, van Meer BL, Pals G, Oldenburg RA, Bekkers JA, Moelker A, de Graaf BM, Matyas G, Frohn-Mulder IM, Timmermans J, Hilhorst-Hofstee Y, Cobben JM, Bruggenwirth HT, van Laer L, Loeys B, De Backer J, Coucke PJ, Dietz HC, Willems PJ, Oostra BA, De Paepe A, Roos-Hesselink JW, Bertoli-Avella AM, Wessels MW (2012) Phenotypic spectrum of the SMAD3-related aneurysms–osteoarthritis syndrome. J Med Genet 49(1):47–57PubMedCrossRefGoogle Scholar
  10. 10.
    Van Laer L, Proost D, Loeys BL (2013) Educational paper: connective tissue disorders with vascular involvement: from gene to therapy. Eur J Pediatr 172(8):997–1005PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Williams JA, Loeys BL, Nwakanma LU, Dietz HC, Spevak PJ, Patel ND, François K, DeBacker J, Gott VL, Vricella LA, Cameron DE (2007) Early surgical experience with Loeys Dietz: a new syndrome of aggressive thoracic aortic aneurysm disease. Ann Thorac Surg 83:S757–S763PubMedCrossRefGoogle Scholar
  12. 12.
    Yang JH, Ki C, Han H, Song BG, Jang SY, Chung T, Sung K, Lee HJ, Kim DK (2012) Clinical features and genetic analysis of Korean patients with Loeys–Dietz syndrome. J Hum Genet 57:52–56PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Teck Wah Ting
    • 1
  • Angeline Hwei Meeng Lai
    • 1
  • Jonathan Tze Liang Choo
    • 2
  • Teng Hong Tan
    • 2
  1. 1.Genetics Service, Department of Paediatric MedicineKK Women’s and Children’s HospitalSingaporeSingapore
  2. 2.Cardiology Service, Department of Paediatric SubspecialtiesKK Women’s and Children’s HospitalSingaporeSingapore

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