DiGeorge Syndrome: Prenatal Diagnosis and Outcome in a Tertiary Care Fetal Medicine Center

Abstract

Introduction DiGeorge syndrome (DGS), caused by defects during embryonic development, is primarily sporadic and detectable via prenatal ultrasound, which reveals features like cardiovascular abnormalities and thymic hypoplasia. Early diagnosis of deletion 22q11.2 aids in effective prenatal, perinatal, and postnatal care management.

Objectives The aim of this series was to delineate the common and unusual sonographic abnormalities as well as outcomes of prenatally diagnosed DiGeorge fetuses from a single tertiary care center.

Methods This is a single center retrospective study of eight fetuses detected in the mid trimester between 2012 and 2020. They were evaluated extensively for anatomic anomalies on ultrasound and diagnosed deletion 22q11.2 using fluorescence in situ hybridization or microarray based comparative genomic hybridization.

Results Congenital heart disease (CHD) was the primary indication for evaluation in six of eight fetuses, while one had a strong family history of DGS. The mean maternal age and gestational age were 33 years 4 months and 19 weeks 3 days, respectively. The majority (5 of 8) had conotruncal heart defects. Three of eight fetuses had extracardiac findings in varying combinations. Hypoplasia of the thymus and small for gestational age were common findings in three of eight fetuses. Lesser known associations like congenital talipes equinovarus (CTEV), choroid plexus (CP) cysts, and clenched fists with pointing index finger were noted in one fetus each, thereby expanding the fetal phenotypic spectrum. Four of eight of the families decided to terminate the pregnancy. Two of eight babies expired and the two surviving infants are doing well with near normal developmental milestones.

Conclusion Though conotruncal CHD is the most consistent finding in DGS prenatally, CTEV, polyhydramnios, clenched fists with pointing index finger, and CP cyst in association with other subtle fetal markers in the absence of CHD should raise a high index of suspicion of DGS prenatally. Early and prompt diagnosis is imperative for counseling families, enabling them in decision making, and to garner knowledge about anticipatory postnatal care.

Keywords

DiGeorge syndrome - deletion 22q11.2 - conotruncal defects - congenital talipes equinovarus - clenched fists - choroid plexuses cysts

Ethical Approval

Ethical approval for this study was granted by the Ethics (Medical Research) Committee Office, Amrita Institute of Medical Sciences & Research Center, Cochin, Kerala, India.

Authors' Contributions

R.M. prepared the manuscript and did detailed literature search. R.E. helped in manuscript preparation. V.K. had conceived the idea of drafting this paper and has done the final drafting and will act as the guarantor of the manuscript.

Publikationsverlauf

Artikel online veröffentlicht:
16. September 2024

• References

• 1 McDonald-McGinn DM, Sullivan KE, Marino B. et al. 22q11.2 deletion syndrome. Nat Rev Dis Primers 2015; 1: 15071
• 2 Levy-Mozziconacci A, Piquet C, Heurtevin PC, Philip N. Prenatal diagnosis of 22q11 microdeletion. Prenat Diagn 1997; 17 (11) 1033-1037
• 3 Moore JW, Binder GA, Berry R. Prenatal diagnosis of aneuploidy and deletion 22q11.2 in fetuses with ultrasound detection of cardiac defects. Am J Obstet Gynecol 2004; 191 (06) 2068-2073
• 4 Tudorache S, Burada F, Florea M, Dragusin R, Patru LC, Iliescu DG. DiGeorge syndrome – importance of the early fetal anatomy assessment and multidisciplinary work-up in prenatal diagnosis. A case report and review of the literature. World J Pharmaceut Med Res 2017; 3 (01) 83-89
• 5 Lackey AE, Muzio MR. DiGeorge Syndrome. In: StatPearls [Internet]; 2022. Accessed august 11, 2024 at: https://www.ncbi.nlm.nih.gov/books/NBK549798/
• 6 Noël AC, Pelluard F, Delezoide AL. et al. Fetal phenotype associated with the 22q11 deletion. Am J Med Genet A 2014; 164A (11) 2724-2731
• 7 Besseau-Ayasse J, Violle-Poirsier C, Bazin A. et al. A French collaborative survey of 272 fetuses with 22q11.2 deletion: ultrasound findings, fetal autopsies and pregnancy outcomes. Prenat Diagn 2014; 34 (05) 424-430
• 8 Schindewolf E, Khalek N, Johnson MP. 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 (08) 1735-1741
• 9 Cascella M, Muzio MR. Early onset intellectual disability in chromosome 22q11.2 deletion syndrome. Rev Chil Pediatr 2015; 86 (04) 283-286
• 10 Zhang Z, Huynh T, Baldini A. Mesodermal expression of Tbx1 is necessary and sufficient for pharyngeal arch and cardiac outflow tract development. Development 2006; 133 (18) 3587-3595
• 11 Guner-Ataman B, González-Rosa JM, Shah HN. et al. Failed progenitor specification underlies the cardiopharyngeal phenotypes in a zebrafish model of 22q11.2 deletion syndrome. Cell Rep 2018; 24 (05) 1342-1354.e5
• 12 Fernandez A, Meechan D, Baker JL, Karpinski BA, LaMantia AS, Maynard TM. 22q11 deletion syndrome: copy number variations and development. Prin Development Genet 2015; 36: 677-696
• 13 Balci S, Altugan FS, Alehan D, Aypar E, Baltaci V. A prenatally sonographically diagnosed conotruncal anomaly with mosaic type trisomy 21 and 22q11.2 microdeletion/DiGeorge syndrome. Genet Couns 2009; 20 (04) 373-377
• 14 Bassett AS, McDonald-McGinn DM, Devriendt K. et al; International 22q11.2 Deletion Syndrome Consortium. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr 2011; 159 (02) 332-9.e1
• 15 Homans JF, Crowley TB, Chen E. et al. Club foot in association with the 22q11.2 deletion syndrome: an observational study. Am J Med Genet A 2018; 176 (10) 2135-2139
• 16 McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore) 2011; 90 (01) 1-18
• 17 Sumitomo A, Horike K, Hirai K. et al. A mouse model of 22q11.2 deletions: molecular and behavioral signatures of Parkinson's disease and schizophrenia. Sci Adv 2018; 4 (08) eaar6637
• 18 Meechan DW, Maynard TM, Tucker ES. et al. Modeling a model: mouse genetics, 22q11.2 deletion syndrome, and disorders of cortical circuit development. Prog Neurobiol 2015; 130: 1-28
• 19 Bakare N, Menschik D, Tiernan R, Hua W, Martin D. Severe combined immunodeficiency (SCID) and rotavirus vaccination: reports to the Vaccine Adverse Events Reporting System (VAERS). Vaccine 2010; 28 (40) 6609-6612
• 20 Davies EG, Cheung M, Gilmour K. et al. Thymus transplantation for complete DiGeorge syndrome: European experience. J Allergy Clin Immunol 2017; 140 (06) 1660-1670.e16
• 21 Bretelle F, Beyer L, Pellissier MC. et al Prenatal and postnatal diagnosis of 22q11.2 deletion syndrome. Eur J Med Genet 2010; 53 (06) 367-370