Clinical Course and Outcome of Prenatally Detected 22q11.2 Deletion Syndrome—A Retrospective Analysis
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Clinical Course
Case Number | GA at Live Birth/TOP, Weeks | Genetic Test for 22q11.2 DS | Deletion Size, Mega Bases | Inheritance | CHD | Thymus Hypo/Aplasia | Genitourinary Anomalies | Skeletal Dysplasia | Cranifacial Anomalies | Cerebral Anomalies | Abdominal Anomalies |
---|---|---|---|---|---|---|---|---|---|---|---|
TOP without feticide | |||||||||||
17 | 20.3 | FISH, CMA | 2.53 | maternal 22q11.2 DS | RAA | yes | Bilateral hydronephrosis | - | - | - | - |
18 | 20.1 | FISH | - | unknown | TOF | yes | - | - | Hypertelorism | - | - |
19 | 22.1 | FISH | - | unknown | TOF | yes | - | - | Hypertelorism, low-set ears, retrognathia | - | - |
20 | 21.9 | FISH, CMA | 2.2 | de novo | Truncus arteriosus | yes | - | - | - | - | - |
21 | 16.4 | FISH | - | de novo | Truncus arteriosus | yes | Bilateral renal agenesis | Malposition and contractures of upper and lower extremities | - | - | - |
CHD | All Cases (n = 21) | Live Births (n = 7) | TOP (n = 14) |
---|---|---|---|
TOF | 8 (38.1%) | 2 (28.6%) | 6 (42.9%) |
RAA | 4 (19.0%) | 2 (28.6%) | 2 (14.3%) |
IAA | 3 (14.3%) | 1 (14.3%) | 2 (14.3%) |
Truncus arteriosus | 3 (14.3%) | 0 (0%) | 3 (21.4%) |
VSD, aortic arch hypoplasia | 2 (9.5%) | 1 (14.3%) | 1 (7.1%) |
DORV, TGA, PA hypoplasia | 1 (4.8%) | 1 (14.3%) | 0 (0%) |
3.2. Fetal Anomalies Diagnosed via MRI
3.3. Genetic Testing
3.4. Pregnancy Outcome and Postpartum Management
3.5. Fetal Anomalies Diagnosed by Autopsy
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Dar, P.; Jacobsson, B.; Clifton, R.; Egbert, M.; Malone, F.; Wapner, R.J.; Roman, A.S.; Khalil, A.; Faro, R.; Madankumar, R.; et al. Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome. Am. J. Obstet. Gynecol. 2022, 227, 79.e1–79.e11. [Google Scholar] [CrossRef]
- Biggs, S.E.; Gilchrist, B.; May, K.R. Chromosome 22q11.2 Deletion (DiGeorge Syndrome): Immunologic Features, Diagnosis, and Management. Curr. Allergy Asthma Rep. 2023, 23, 213–222. [Google Scholar] [CrossRef] [PubMed]
- Grati, F.R.; Molina Gomes, D.; Ferreira, J.C.; Dupont, C.; Alesi, V.; Gouas, L.; Horelli-Kuitunen, N.; Choy, K.W.; García-Herrero, S.; de la Vega, A.G.; et al. Prevalence of recurrent pathogenic microdeletions and microduplications in over 9500 pregnancies. Prenat. Diagn. 2015, 35, 801–809. [Google Scholar] [CrossRef] [PubMed]
- Cirillo, A.; Lioncino, M.; Maratea, A.; Passariello, A.; Fusco, A.; Fratta, F.; Monda, E.; Caiazza, M.; Signore, G.; Esposito, A.; et al. Clinical Manifestations of 22q11.2 Deletion Syndrome. Heart Fail. Clin. 2022, 18, 155–164. [Google Scholar] [CrossRef] [PubMed]
- Lin, A.; Ching, C.R.K.; Vajdi, A.; Sun, D.; Jonas, R.K.; Jalbrzikowski, M.; Kushan-Wells, L.; Pacheco Hansen, L.; Krikorian, E.; Gutman, B.; et al. Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry. J. Neurosci. 2017, 37, 6183–6199. [Google Scholar] [CrossRef] [Green Version]
- Cortés-Martín, J.; Peñuela, N.L.; Sánchez-García, J.C.; Montiel-Troya, M.; Díaz-Rodríguez, L.; Rodríguez-Blanque, R. Deletion Syndrome 22q11.2: A Systematic Review. Children 2022, 9, 1168. [Google Scholar] [CrossRef]
- Kowalczyk, K.; Bartnik-Głaska, M.; Smyk, M.; Plaskota, I.; Bernaciak, J.; Kędzior, M.; Wiśniowiecka-Kowalnik, B.; Jakubów-Durska, K.; Braun-Walicka, N.; Barczyk, A.; et al. Prenatal Diagnosis by Array Comparative Genomic Hybridization in Fetuses with Cardiac Abnormalities. Genes 2021, 12, 2021. [Google Scholar] [CrossRef]
- Blagowidow, N.; Nowakowska, B.; Schindewolf, E.; Grati, F.R.; Putotto, C.; Breckpot, J.; Swillen, A.; Crowley, T.B.; Loo, J.C.Y.; Lairson, L.A.; et al. Prenatal Screening and Diagnostic Considerations for 22q11.2 Microdeletions. Genes 2023, 14, 160. [Google Scholar] [CrossRef]
- McDonald-McGinn, D.M.; Sullivan, K.E.; Marino, B.; Philip, N.; Swillen, A.; Vorstman, J.A.; Zackai, E.H.; Emanuel, B.S.; Vermeesch, J.R.; Morrow, B.E.; et al. 22q11.2 deletion syndrome. Nat. Rev. Dis. Prim. 2015, 1, 15071. [Google Scholar] [CrossRef] [Green Version]
- Goldmuntz, E. 22q11.2 deletion syndrome and congenital heart disease. Am. J. Med. Genet. C Semin. Med. Genet. 2020, 184, 64–72. [Google Scholar] [CrossRef]
- Monteiro, M.; Aires, T.; Pimentel, K.; Pedrosa, K.; Lima, S.; Aquino, M.; Leiróz, R.; Araujo Júnior, E.; Sarno, M. Ultrasonographic evaluation of the fetal thymic-thoracic ratio and its association with conotruncal heart defects. J. Gynecol. Obstet. Hum. Reprod. 2022, 51, 102281. [Google Scholar] [CrossRef]
- Bataeva, R.; Bellsham-Revell, H.; Zidere, V.; Allan, L.D. Reliability of fetal thymus measurement in prediction of 22q11.2 deletion: A retrospective study using four-dimensional spatiotemporal image correlation volumes. Ultrasound Obstet. Gynecol. 2013, 41, 172–176. [Google Scholar] [CrossRef]
- Chaoui, R.; Heling, K.S.; Lopez, A.S.; 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. [Google Scholar] [CrossRef] [PubMed]
- Besseau-Ayasse, J.; Violle-Poirsier, C.; Bazin, A.; Gruchy, N.; Moncla, A.; Girard, F.; Till, M.; Mugneret, F.; Coussement, A.; Pelluard, 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. [Google Scholar] [CrossRef] [PubMed]
- Hillman, S.C.; Pretlove, S.; Coomarasamy, A.; McMullan, D.J.; Davison, E.V.; Maher, E.R.; Kilby, M.D. Additional information from array comparative genomic hybridization technology over conventional karyotyping in prenatal diagnosis: A systematic review and meta-analysis. Ultrasound Obstet. Gynecol. 2011, 37, 6–14. [Google Scholar] [CrossRef] [PubMed]
- Gonçalves, L.F.; Lee, W.; Mody, S.; Shetty, A.; Sangi-Haghpeykar, H.; Romero, R. Diagnostic accuracy of ultrasonography and magnetic resonance imaging for the detection of fetal anomalies: A blinded case-control study. Ultrasound Obstet. Gynecol. 2016, 48, 185–192. [Google Scholar] [CrossRef] [Green Version]
- Griffiths, P.D.; Bradburn, M.; Campbell, M.J.; Cooper, C.L.; Embleton, N.; Graham, R.; Hart, A.R.; Jarvis, D.; Kilby, M.D.; Lie, M.; et al. MRI in the diagnosis of fetal developmental brain abnormalities: The MERIDIAN diagnostic accuracy study. Health Technol. Assess. 2019, 23, 1–144. [Google Scholar] [CrossRef]
- Pylypjuk, C.L.; Memon, S.F.; Chodirker, B.N. Utility of Measuring Fetal Cavum Septum Pellucidum (CSP) Width During Routine Obstetrical Ultrasound for Improving Diagnosis of 22q11.2 Deletion Syndrome: A Case-Control Study. Appl. Clin. Genet. 2022, 15, 87–95. [Google Scholar] [CrossRef]
- Sarac Sivrikoz, T.; Basaran, S.; Has, R.; Karaman, B.; Kalelioglu, I.H.; Kirgiz, M.; Altunoglu, U.; Yuksel, A. Prenatal sonographic and cytogenetic/molecular findings of 22q11.2 microdeletion syndrome in 48 confirmed cases in a single tertiary center. Arch. Gynecol. Obstet. 2022, 305, 323–342. [Google Scholar] [CrossRef]
- Unolt, M.; Versacci, P.; Anaclerio, S.; Lambiase, C.; Calcagni, G.; Trezzi, M.; Carotti, A.; Crowley, T.B.; Zackai, E.H.; Goldmuntz, E.; 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. [Google Scholar] [CrossRef]
- Schindewolf, E.; Khalek, N.; Johnson, M.P.; Gebb, J.; Coleman, B.; Crowley, T.B.; Zackai, E.H.; McDonald-McGinn, D.M.; Moldenhauer, J.S. 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. [Google Scholar] [CrossRef]
- Alberry, M.S.; Aziz, E.; Ahmed, S.R.; Abdel-Fattah, S. Non invasive prenatal testing (NIPT) for common aneuploidies and beyond. Eur. J. Obstet. Gynecol. Reprod. Biol. 2021, 258, 424–429. [Google Scholar] [CrossRef] [PubMed]
- Soster, E.; Dyr, B.; Rafalko, J.; Almasri, E.; Cacheris, P. Positive cfDNA screening results for 22q11.2 deletion syndrome-Clinical and laboratory considerations. Front. Genet. 2023, 14, 1146669. [Google Scholar] [CrossRef] [PubMed]
- Noël, A.C.; Pelluard, F.; Delezoide, A.L.; Devisme, L.; Loeuillet, L.; Leroy, B.; Martin, A.; Bouvier, R.; Laquerriere, A.; Jeanne-Pasquier, C.; et al. Fetal phenotype associated with the 22q11 deletion. Am. J. Med. Genet. A 2014, 164a, 2724–2731. [Google Scholar] [CrossRef] [PubMed]
- Goncalves, L.F.; Lindblade, C.L.; Cornejo, P.; Patel, M.C.; McLaughlin, E.S.; Bardo, D.M.E. Contribution of fetal magnetic resonance imaging in fetuses with congenital heart disease. Pediatr. Radiol. 2022, 52, 513–526. [Google Scholar] [CrossRef]
- Rossi, A.C.; Prefumo, F. Additional value of fetal magnetic resonance imaging in the prenatal diagnosis of central nervous system anomalies: A systematic review of the literature. Ultrasound Obstet. Gynecol. 2014, 44, 388–393. [Google Scholar] [CrossRef]
- Szczawińska-Popłonyk, A.; Schwartzmann, E.; Chmara, Z.; Głukowska, A.; Krysa, T.; Majchrzycki, M.; Olejnicki, M.; Ostrowska, P.; Babik, J. Chromosome 22q11.2 Deletion Syndrome: A Comprehensive Review of Molecular Genetics in the Context of Multidisciplinary Clinical Approach. Int. J. Mol. Sci. 2023, 24, 8317. [Google Scholar] [CrossRef]
- Michaelovsky, E.; Frisch, A.; Carmel, M.; Patya, M.; Zarchi, O.; Green, T.; Basel-Vanagaite, L.; Weizman, A.; Gothelf, D. Genotype-phenotype correlation in 22q11.2 deletion syndrome. BMC Med. Genet. 2012, 13, 122. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jing, X.Y.; Zhang, Y.L.; Zhen, L.; Li, Y.L.; Li, D.Z. Prenatal sonographic findings in a cohort of foetuses with a confirmed 22q11.2 microdeletion at a single Chinese Tertiary Centre. J. Obstet. Gynaecol. 2022, 42, 2935–2940. [Google Scholar] [CrossRef]
- Rossi, A.C.; Prefumo, F. Correlation between fetal autopsy and prenatal diagnosis by ultrasound: A systematic review. Eur. J. Obstet. Gynecol. Reprod. Biol. 2017, 210, 201–206. [Google Scholar] [CrossRef]
- Ozdemir, O.; Aksoy, F.; Sen, C. Fetal autopsy for the diagnosis of skeletal dysplasia and comparison with prenatal ultrasound findings over a 16-year period. J. Perinat. Med. 2022, 50, 1239–1247. [Google Scholar] [CrossRef]
- Ozdemir, O.; Aksoy, F.; Sen, C. Dilemma after termination of pregnancy due to urogenital fetal anomalies: Discrepancy between prenatal ultrasonographic diagnosis and autopsy. Int. J. Gynaecol. Obstet. 2022, 159, 223–228. [Google Scholar] [CrossRef]
- Akgun, H.; Basbug, M.; Ozgun, M.T.; Canoz, O.; Tokat, F.; Murat, N.; Ozturk, F. Correlation between prenatal ultrasound and fetal autopsy findings in fetal anomalies terminated in the second trimester. Prenat. Diagn. 2007, 27, 457–462. [Google Scholar] [CrossRef]
n = 21 | |
---|---|
Maternal age, years a | 33 (31–35) |
Maternal BMI a | 23 (21–26) |
Primiparous b | 14 (66.7%) |
Prenatal MRI b | 10 (47.6%) |
CVS/PB b | 6 (28.6%) |
AC b | 15 (71.4%) |
ART b | 2 (9.5%) |
All Cases (n = 21) | Live Births (n = 7) | TOP (n = 14) | |
---|---|---|---|
GA at invasive testing, weeks a | 22.0 (19.7–22.9) | 23.3 (22.0–25.0) | 21.4 (16.6–22.1) |
GA at diagnosis, weeks a | 23.0 (21.4–24.8) | 25.3 (23.1–26.9) | 21.8 (19.8–23.3) |
CHD b | 21 (100%) | 7 (100%) | 14 (100%) |
thymus hypo/aplasia b | 19 (90.4%) | 7 (100%) | 12 (85.7%) |
genitourinary anomaly b | 5 (23.8%) | 3 (42.9%) | 2 (14.3%) |
cerebral anomaly b | 2 (9.5%) | 1 (14.3%) | 1 (7.1%) |
skeletal dysplasia b | 1 (4.8%) | 0 (0%) | 1 (7.1%) |
craniofacial anomaly b | 1 (4.8%) | 0 (0%) | 1 (7.1%) |
abdominal anomaly b | 1 (4.8%) | 1 (14.3%) | 0 (0%) |
polyhydramnios b | 8 (38.1%) | 5 (71.4%) | 3 (21.4%) |
Case Number | GA at Live Birth/TOP, Weeks | Genetic Test for 22q11.2 DS | Deletion Size, Mega Bases | Inheritance | CHD | Thymuys Hypo/Aplasia | Genitourinary Anomalies | Skeletal Dysplasia | Cranifacial Anomalies | Cerebral Anomalies | Abdominal Anomalies |
---|---|---|---|---|---|---|---|---|---|---|---|
Live birth | |||||||||||
1 | 39.6 | FISH, CMA | 2.16 | de novo | TOF | yes | Unilateral polycystic kidney | - | - | - | - |
2 | 38.4 | FISH, CMA | 2.25 | de novo | TOF | yes | Unilateral hydronephrosis | - | - | Polymicrogyria | - |
3 | 37.9 | MLPA, CMA | 3.2 | de novo | VSD, aortic arch hypoplasia | yes | - | - | - | - | - |
4 | 36.4 | MLPA, CMA | 9.6 | maternal translocation 8/22 | DORV, TGA, PA hypoplasia | yes | - | - | - | - | - |
5 | 38.0 | FISH, MLPA, CMA | - | de novo | IAA | yes | - | - | - | - | - |
6 | 40.9 | FISH | - | unknown | IAA | yes | Unilateral hydronephrosis | - | - | - | - |
7 | 37.2 | MLPA | - | de novo | RAA | yes | - | - | - | - | - |
Case Number | GA at Live Birth/TOP, Weeks | Genetic Test for 22q11.2 DS | Deletion Size, Mega Bases | Inheritance | CHD | Thymuys Hypo/Aplasia | Genitourinary Anomalies | Skeletal Dysplasia | Cranifacial Anomalies | Cerebral Anomalies | Abdominal Anomalies |
---|---|---|---|---|---|---|---|---|---|---|---|
TOP with feticide | |||||||||||
8 | 24.9 | FISH, CMA | 2.18 | de novo | TOF | yes | - | - | - | - | - |
9 | 24.6 | FISH, CMA | 2.2 | de novo | RAA | yes | - | - | Hypertelorism | - | - |
10 | 26.0 | FISH, CMA | 1.4 | de novo | TOF | yes | - | - | Hypertelorism, low-set ears | - | - |
11 | 23.6 | FISH | - | de novo | VSD, aortic arch hypoplasia | yes | - | Malposition of upper extremities | Low-set ears, micrognathia | Mega cisterna magna | - |
12 | 26.0 | FISH | - | unknown | IAA | yes | - | - | Hypertelorism, low-set ears, micrognathia | - | Liver cyst, hepatosplenomegaly |
13 | 26.4 | FISH | - | de novo | Truncus arteriosus | yes | - | - | Hypertelorism, low-set ears, micrognathia, mild cleft palate | - | - |
14 | 22.3 | FISH | - | unknown | RAA | yes | - | Talipes | - | - | - |
15 | 23.6 | FISH | - | unknown | TOF | yes | - | - | Hypertelorism, low-set ears, micrognathia | - | - |
16 | 24.0 | FISH | de novo | TOF | yes | Cryptorchidism | - | - |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Paternostro, C.; Springer, S.; Kasprian, G.; Yerlikaya-Schatten, G.; Reischer, T. Clinical Course and Outcome of Prenatally Detected 22q11.2 Deletion Syndrome—A Retrospective Analysis. Diagnostics 2023, 13, 2244. https://doi.org/10.3390/diagnostics13132244
Paternostro C, Springer S, Kasprian G, Yerlikaya-Schatten G, Reischer T. Clinical Course and Outcome of Prenatally Detected 22q11.2 Deletion Syndrome—A Retrospective Analysis. Diagnostics. 2023; 13(13):2244. https://doi.org/10.3390/diagnostics13132244
Chicago/Turabian StylePaternostro, Chiara, Stephanie Springer, Gregor Kasprian, Gülen Yerlikaya-Schatten, and Theresa Reischer. 2023. "Clinical Course and Outcome of Prenatally Detected 22q11.2 Deletion Syndrome—A Retrospective Analysis" Diagnostics 13, no. 13: 2244. https://doi.org/10.3390/diagnostics13132244
APA StylePaternostro, C., Springer, S., Kasprian, G., Yerlikaya-Schatten, G., & Reischer, T. (2023). Clinical Course and Outcome of Prenatally Detected 22q11.2 Deletion Syndrome—A Retrospective Analysis. Diagnostics, 13(13), 2244. https://doi.org/10.3390/diagnostics13132244