Obstet Gynecol Sci.  2020 Apr;63(3):330-336. 10.5468/ogs.2020.63.3.330.

Prenatal screening of DiGeorge (22q11.2 deletion) syndrome by abnormalities of the great arteries among Thai pregnant women

• Traisrisilp K
• Tongprasert F
• Srisupundit K
• Luewan S
• Tongsong T

• KMID: 2500423
• DOI: http://doi.org/10.5468/ogs.2020.63.3.330

Abstract

Objective
22q11.2DS (deletion syndrome) is one of the common serious anomalies resulting in high perinatal morbidity and mortality rate. Nevertheless, prenatal diagnosis of 22q11.2DS in Southeast Asia has never been described and its prevalence in prenatal series has never been explored. The objective of this study was to describe the experience of prenatal diagnosis of 22q11.2DS in the Thai population and to determine its prevalence among fetuses prenatally diagnosed with abnormalities of the great arteries.
Methods
A prospective study was conducted on pregnant Thai women prenatally diagnosed with abnormalities of the great arteries in the second trimester. The recruited cases were investigated for fetal 22q11.2 deletion by in situ hybridization with a probe specific to the DiGeorge/VCFS TUPLE 1 region located on chromosome 22 for the locus D22S75, and 22qter for a telomere specific sequence clone as the control region.
Results
Five out of the 42 (11.9%) fetuses with abnormalities of the great arteries meeting the inclusion criteria were proven to have 22q11.2DS. The most common abnormalities were the tetralogy of Fallot (or variants) and right-sided aortic arch, followed by a thymic hypoplasia.
Conclusion
As observed in the western countries, we have documented that, among pregnant Thai women, 22q11.2DS is highly prevalent in fetuses with abnormalities of the great arteries (approximately 12%). This information is important when counselling couples to undergo prenatal testing for 22q11.2DS, since this information is vital in the patients' decision of termination or continuation of pregnancy and in a well-prepared management of the affected child.

Keyword

22q11.2 deletion syndrome; Congenital heart defect; DiGeorge syndrome; Right aortic arch; Thymus

Figure

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  Fig. 1 Examples of the findings of fetuses with 22q11.2DS: prenatal ultrasound findings of double-outlet right ventricle (A: Case 4), and right-sided aortic arch with relatively small thymus (B: Case 5); and pathological findings of absent pulmonary valve (C: Case 3) and right-sided aortic arch (D: Case 5). Asterisk (*) presented pulmonary annulus.LV, left ventricle; RV, right ventricle; Ao, aorta; PA, pulmonary artery; S, superior vena cava; SCA, subclavian artery; CCA, common carotid.

Reference

1. Bassett AS, McDonald-McGinn DM, Devriendt K, Digilio MC, Goldenberg P, Habel A, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011; 159:332–339.e1. PMID: 21570089.

2. Besseau-Ayasse J, Violle-Poirsier C, Bazin A, Gruchy N, Moncla A, Girard F, et al. A French collaborative survey of 272 fetuses with 22q11.2 deletion: ultrasound findings, fetal autopsies and pregnancy outcomes. Prenat Diagn. 2014; 34:424–430. PMID: 24395195.

3. Noël AC, Pelluard F, Delezoide AL, Devisme L, Loeuillet L, Leroy B, et al. Fetal phenotype associated with the 22q11 deletion. Am J Med Genet A. 2014; 164A:2724–2731. PMID: 25111715.

4. Schindewolf E, Khalek N, Johnson MP, Gebb J, Coleman B, Crowley TB, et al. Expanding the fetal phenotype: Prenatal sonographic findings and perinatal outcomes in a cohort of patients with a confirmed 22q11.2 deletion syndrome. Am J Med Genet A. 2018; 176:1735–1741. PMID: 30055034.

5. Nickel RE, Magenis RE. Neural tube defects and deletions of 22q11. Am J Med Genet. 1996; 66:25–27. PMID: 8957506.

6. Wichajam K, Kampan J. Difference of clinical phenotypes and immunological features of 22q11.2 deletion syndrome in north-eastern Thai children compare to western countries. J Med Assoc Thai. 2014; 97(Suppl 10):S59–S66.

7. Ruangdaraganon N, Tocharoentanaphol C, Khowsathit P, Sombuntham T, Pongpanich B. Chromosome 22q11 deletion syndrome: the first three cases reported in Thailand. J Med Assoc Thai. 1999; 82(Suppl 1):S179–S185. PMID: 10730540.

8. Kruszka P, Addissie YA, McGinn DE, Porras AR, Biggs E, Share M, et al. 22q11.2 deletion syndrome in diverse populations. Am J Med Genet A. 2017; 173:879–888. PMID: 28328118.

9. Korpaisarn S, Trachoo O, Sriphrapradang C. Chromosome 22q11.2 deletion syndrome presenting as adult onset hypoparathyroidism: clues to diagnosis from dysmorphic facial features. Case Rep Endocrinol. 2013; 2013:802793. PMID: 23738156.

10. Lee MY, Won HS, Baek JW, Cho JH, Shim JY, Lee PR, et al. Variety of prenatally diagnosed congenital heart disease in 22q11.2 deletion syndrome. Obstet Gynecol Sci. 2014; 57:11–16. PMID: 24596813.

11. Kong CW, Cheng YK, To WW, Leung TY. Prevalence of chromosomal abnormalities and 22q11.2 deletion in conotruncal and non-conotruncal antenatally diagnosed congenital heart diseases in a Chinese population. Hong Kong Med J. 2019; 25:6–12.

12. Momma K. Cardiovascular anomalies associated with chromosome 22q11.2 deletion syndrome. Am J Cardiol. 2010; 105:1617–1624. PMID: 20494672.

13. Unolt M, Versacci P, Anaclerio S, Lambiase C, Calcagni G, Trezzi M, et al. Congenital heart diseases and cardiovascular abnormalities in 22q11.2 deletion syndrome: From well-established knowledge to new frontiers. Am J Med Genet A. 2018; 176:2087–2098. PMID: 29663641.

14. Bassett AS, Chow EW, Husted J, Hodgkinson KA, Oechslin E, Harris L, et al. Premature death in adults with 22q11.2 deletion syndrome. J Med Genet. 2009; 46:324–330. PMID: 19246480.

15. McElhinney DB, Clark BJ 3rd, Weinberg PM, Kenton ML, McDonald-McGinn D, Driscoll DA, et al. Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and branching. J Am Coll Cardiol. 2001; 37:2114–2119. PMID: 11419896.

16. Fung WL, Butcher NJ, Costain G, Andrade DM, Boot E, Chow EW, et al. Practical guidelines for managing adults with 22q11.2 deletion syndrome. Genet Med. 2015; 17:599–609. PMID: 25569435.

17. Fokstuen S, Bottani A, Medeiros PF, Antonarakis SE, Stoll C, Schinzel A. Laryngeal atresia type III (glottic web) with 22q11.2 microdeletion: report of three patients. Am J Med Genet. 1997; 70:130–133. PMID: 9128930.

18. Leopold C, De Barros A, Cellier C, Drouin-Garraud V, Dehesdin D, Marie JP. Laryngeal abnormalities are frequent in the 22q11 deletion syndrome. Int J Pediatr Otorhinolaryngol. 2012; 76:36–40. PMID: 22019154.

19. Sacca R, Zur KB, Crowley TB, Zackai EH, Valverde KD, McDonald-McGinn DM. Association of airway abnormalities with 22q11.2 deletion syndrome. Int J Pediatr Otorhinolaryngol. 2017; 96:11–14. PMID: 28390597.

20. Chaoui R, Heling KS, Lopez AS, Thiel G, Karl K. The thymic-thoracic ratio in fetal heart defects: a simple way to identify fetuses at high risk for microdeletion 22q11. Ultrasound Obstet Gynecol. 2011; 37:397–403. PMID: 21308838.

21. Pittyanont S, Luewan S, Tongsong T. Cardio-STIC based reference ranges of fetal thymus size in singleton pregnancies. J Ultrasound Med. 2017; 36:1181–1188. PMID: 28224652.

22. Burtey S. 22q11.2 microdeletion syndrome is a common cause of renal tract malformations. Nat Clin Pract Nephrol. 2008; 4:E1.

23. Digilio MC, Marino B, Grazioli S, Agostino D, Giannotti A, Dallapiccola B. Comparison of occurrence of genetic syndromes in ventricular septal defect with pulmonic stenosis (classic tetralogy of Fallot) versus ventricular septal defect with pulmonic atresia. Am J Cardiol. 1996; 77:1375–1376. PMID: 8677886.

24. Goldmuntz E, Clark BJ, Mitchell LE, Jawad AF, Cuneo BF, Reed L, et al. Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol. 1998; 32:492–498. PMID: 9708481.

25. Marino B, Digilio MC, Toscano A, Anaclerio S, Giannotti A, Feltri C, et al. Anatomic patterns of conotruncal defects associated with deletion 22q11. Genet Med. 2001; 3:45–48. PMID: 11339377.

26. Peyvandi S, Lupo PJ, Garbarini J, Woyciechowski S, Edman S, Emanuel BS, et al. 22q11.2 deletions in patients with conotruncal defects: data from 1,610 consecutive cases. Pediatr Cardiol. 2013; 34:1687–1694. PMID: 23604262.