Loeys‑Dietz syndrome associated with a heterozygous mutation in <em>TGFBR2</em> in a female infant: A case report

Zhu,Chun; Tong,Meiling; Chi,Xia

doi:10.3892/etm.2020.9444

Loeys‑Dietz syndrome associated with a heterozygous mutation in TGFBR2 in a female infant: A case report

Authors:
- Chun Zhu
- Meiling Tong
- Xia Chi
View Affiliations

Affiliations: Department of Child Health Care, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
Published online on: November 4, 2020 https://doi.org/10.3892/etm.2020.9444
Article Number: 12

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Loeys‑Dietz syndrome (LDS) is an unusual hereditary connective tissue disease with no clear standard clinical diagnosis. The present report describes a case of an infant diagnosed with LDS at the age of 2 months and 23 days. To the best of our knowledge, this case represents the youngest reported case of LDS in China. Whole exome sequencing revealed a heterozygous variation, c.1441(exon 6)G>A [p.E481k(p.Glu481Lys) (NM_001024847)], located at chr3:30715708 in the transforming growth factor β receptor 2 gene. The patient underwent systematic rehabilitation and standard high‑risk infant follow‑up. Currently, the overall development of the patient continues to improve. The patient can walk with assistance, stand up on her feet unaided, exhibits improved optical line of sight and both eyes can move up and down, side to side (left and right) and track moving objects. The parents have been advised that a further echocardiogram should be performed as soon as possible and regular follow‑up sessions with a cardiovascular specialist are ongoing. LDS diagnosis was confirmed in the patient based on collective findings of skeletal system changes, ocular hypertelorism, ocular exotropia, micrognathia and high‑vaulted palate, in combination with a specific pathogenic gene mutation.

View Figures

View References

1	Van Laer L, Dietz H and Loeys B: Loeys-Dietz syndrome. Adv Exp Med Biol. 802:95–105. 2014.PubMed/NCBI View Article : Google Scholar
2	Loeys BL and Dietz HC: Loeys-Dietz Syndrome. 2008 Feb 28 [Updated 2013 Jul. 11]. In: GeneReviews^™ [Internet]. Pagon RA, Adam MP, Bird TD, et al (eds) University of Washington, Seattle, WA, 1993-2013. Available from: urihttps://www.ncbi.nlm.nih.gov/books/NBK1133/simplehttps://www.ncbi.nlm.nih.gov/books/NBK1133/.
3	Ritelli M, Chiarelli N, Dordoni C, Quinzani S, Venturini M, Maroldi R, Calzavara-Pinton P and Colombi M: Further delineation of Loeys-Dietz syndrome type 4 in a family with mild vascular involvement and a TGFB2 splicing mutation. BMC Med Genet. 15(91)2014.PubMed/NCBI View Article : Google Scholar
4	Maleszewski JJ, Miller DV, Lu J, Dietz HC and Halushka MK: Histopathologic findings in ascending aortas from individuals with Loeys-Dietz syndrome (LDS). Am J Surg Pathol. 33:194–201. 2009.PubMed/NCBI View Article : Google Scholar
5	Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, et al: A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 37:275–281. 2005.PubMed/NCBI View Article : Google Scholar
6	Yang H, Ma Y, Luo M, Zhu G, Zhang Y, Li B, Shu C and Zhou Z: Genetic profiling and cardiovascular phenotypic spectrum in a Chinese cohort of Loeys-Dietz syndrome patients. Orphanet J Rare Dis. 15(6)2020.PubMed/NCBI View Article : Google Scholar
7	Singh KK, Rommel K, Mishra A, Karck M, Haverich A, Schmidtke J and Arslan-Kirchner M: TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome. Hum Mutat. 27:770–777. 2006.PubMed/NCBI View Article : Google Scholar
8	MacCarrick G, Black JH III, Bowdin S, El-Hamamsy I, Frischmeyer-Guerrerio PA, Guerrerio AL, Sponseller PD, Loeys B and Dietz HC III: Loeys-Dietz syndrome: A primer for diagnosis and management. Genet Med. 16:576–587. 2014.PubMed/NCBI View Article : Google Scholar
9	Van Hemelrijk C, Renard M and Loeys B: The Loeys-Dietz syndrome: An update for the clinician. Curr Opin Cardiol. 25:546–551. 2010.PubMed/NCBI View Article : Google Scholar
10	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, et al: Phenotypic spectrum of the SMAD3-related aneurysms-osteoarthritis syndrome. J Med Genet. 49:47–57. 2012.PubMed/NCBI View Article : Google Scholar
11	Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, De Backer JF, Oswald GL, Symoens S, Manouvrier S, et al: Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 355:788–798. 2006.PubMed/NCBI View Article : Google Scholar
12	Van Laer L, Proost D and Loeys BL: Educational paper. Connective tissue disorders with vascular involvement: From gene to therapy. Eur J Pediatr. 172:997–1005. 2013.PubMed/NCBI View Article : Google Scholar
13	Malhotra A and Westesson PL: Loeys-Dietz syndrome. Pediatr Radiol. 39(1015)2009.PubMed/NCBI View Article : Google Scholar
14	Williams JA, Loeys BL, Nwakanma LU, Dietz HC, Spevak PJ, Patel ND, François K, DeBacker J, Gott VL, Vricella LA and Cameron DE: Early surgical experience with Loeys-Dietz: A new syndrome of aggressive thoracic aortic aneurysm disease. Ann Thorac Surg. 83:S757–S763, S785-S790. 2007.PubMed/NCBI View Article : Google Scholar
15	Patel ND, Crawford T, Magruder JT, Alejo DE, Hibino N, Black J, Dietz HC, Vricella LA and Cameron DE: Cardiovascular operations for Loeys-Dietz syndrome: Intermediate-term results. J Thorac Cardiovasc Surg. 153:406–412. 2017.PubMed/NCBI View Article : Google Scholar
16	Krohg-Sørensen K, Lingaas PS, Lundblad R, Seem E, Paus B and Geiran OR: Cardiovascular surgery in Loeys-Dietz syndrome types 1-4. Eur J Cardiothorac Surg. 52:1125–1131. 2017.PubMed/NCBI View Article : Google Scholar