Fetal Agenesis of Corpus Callosum: Chromosomal Copy Number Abnormalities and Postnatal Follow-up

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2024 Jul 30

PMID 39080034

Authors

Meiying Cai

Na Lin

Meimei Fu

Yanting Que

Hailong Huang

Liangpu Xu

Affiliations

Soon will be listed here.

Abstract

Objective: Agenesis of the corpus callosum (ACC) is an anomaly that can occur in fetuses during pregnancy. However, there is currently no treatment for fetal ACC. Therefore, we conducted a retrospective analysis of obstetric outcomes of fetal ACC to explore the relationship between fetal ACC phenotypes and chromosomal copy number abnormalities.

Methods And Results: Amniotic fluid or umbilical cord blood were extracted from pregnant women with fetal ACC for karyotype analysis and chromosomal microarray analysis (CMA). Among the 48 fetuses with ACC, 22 (45.8%, 22/48) had isolated ACC, and 26 (54.2%, 26/48) had non-isolated ACC. Chromosomal abnormalities were detected via karyotype analysis in four cases. In addition to the four cases of pathogenic copy number variations (CNVs) detected using karyotype analysis, CMA revealed two cases of pathogenic CNVs with 17q12 microduplication and 16p12.2 microdeletion. The obstetric outcomes of 26 patients with non-isolated ACC were followed up, and 17 chose to terminate the pregnancy. In addition, seven of the nine cases with non-isolated ACC showed no obvious abnormality during postnatal follow-up, whereas only one case with normal CMA showed an abnormal phenotype at six months. Of the 22 patients with isolated ACC, six chose to terminate the pregnancy. Postnatal follow-up of 16 isolated ACC cases revealed only one with benign CNV, presenting with intellectual disability.

Conclusion: Pregnant women with fetal ACC should be offered prenatal CMA, particularly non-isolated ACC. Patients with ACC should undergo prolonged postnatal follow-up, and appropriate intervention should be provided if necessary.

References

Moradi B, Taherian R, Tahmasebpour A, Taheri M, Kazemi M, Pak N . Fetal corpus callosum abnormalities: Ultrasound and magnetic resonance imaging role. J Clin Ultrasound. 2022; 50(7):989-1003. DOI: 10.1002/jcu.23212. View

Vasudevan C, McKechnie L, Levene M . Long-term outcome of antenatally diagnosed agenesis of corpus callosum and cerebellar malformations. Semin Fetal Neonatal Med. 2012; 17(5):295-300. DOI: 10.1016/j.siny.2012.07.001. View

Miyamoto S, Kato M, Hiraide T, Shiohama T, Goto T, Hojo A . Comprehensive genetic analysis confers high diagnostic yield in 16 Japanese patients with corpus callosum anomalies. J Hum Genet. 2021; 66(11):1061-1068. DOI: 10.1038/s10038-021-00932-y. View

Wright A, Booth R . Neuropsychological profiles of children with agenesis of the corpus callosum: A scoping review. Dev Med Child Neurol. 2023; 65(9):1141-1149. DOI: 10.1111/dmcn.15532. View

Khadija B, Rjiba K, Dimassi S, Dahleb W, Kammoun M, Hannechi H . Clinical and molecular characterization of 1q43q44 deletion and corpus callosum malformations: 2 new cases and literature review. Mol Cytogenet. 2022; 15(1):42. PMC: 9528098. DOI: 10.1186/s13039-022-00620-2. View

de Koning M, Hoffer M, Nibbeling E, Bijlsma E, Toirkens M, Adama-Scheltema P . Prenatal exome sequencing: A useful tool for the fetal neurologist. Clin Genet. 2021; 101(1):65-77. PMC: 9297851. DOI: 10.1111/cge.14070. View

Badaruddin D, Andrews G, Bolte S, Schilmoeller K, Schilmoeller G, Paul L . Social and behavioral problems of children with agenesis of the corpus callosum. Child Psychiatry Hum Dev. 2007; 38(4):287-302. DOI: 10.1007/s10578-007-0065-6. View

Shwe W, Schlatterer S, Williams J, du Plessis A, Mulkey S . Outcome of Agenesis of the Corpus Callosum Diagnosed by Fetal MRI. Pediatr Neurol. 2022; 135:44-51. DOI: 10.1016/j.pediatrneurol.2022.07.007. View

Santo S, DAntonio F, Homfray T, Rich P, Pilu G, Bhide A . Counseling in fetal medicine: agenesis of the corpus callosum. Ultrasound Obstet Gynecol. 2012; 40(5):513-21. DOI: 10.1002/uog.12315. View

10.

Panzaru M, Popa S, Lupu A, Gavrilovici C, Lupu V, Gorduza E . Genetic heterogeneity in corpus callosum agenesis. Front Genet. 2022; 13:958570. PMC: 9562966. DOI: 10.3389/fgene.2022.958570. View

11.

Alamillo C, Powis Z, Farwell K, Shahmirzadi L, Weltmer E, Turocy J . Exome sequencing positively identified relevant alterations in more than half of cases with an indication of prenatal ultrasound anomalies. Prenat Diagn. 2015; 35(11):1073-8. DOI: 10.1002/pd.4648. View

12.

Rai B, Sharif F . Cervicomedullary spinal stenosis and ventriculomegaly in a child with developmental delay due to chromosome 16p12.1 microdeletion syndrome. J Child Neurol. 2014; 30(3):394-6. DOI: 10.1177/0883073814533149. View

13.

Sotiriadis A, Makrydimas G . Neurodevelopment after prenatal diagnosis of isolated agenesis of the corpus callosum: an integrative review. Am J Obstet Gynecol. 2012; 206(4):337.e1-5. DOI: 10.1016/j.ajog.2011.12.024. View

14.

Li X, Wang Q . Magnetic Resonance Imaging (MRI) Diagnosis of Fetal Corpus Callosum Abnormalities and Follow-up Analysis. J Child Neurol. 2021; 36(11):1017-1026. DOI: 10.1177/08830738211016253. View

15.

Sherr E, Owen R, Albertson D, Pinkel D, Cotter P, Slavotinek A . Genomic microarray analysis identifies candidate loci in patients with corpus callosum anomalies. Neurology. 2005; 65(9):1496-8. DOI: 10.1212/01.wnl.0000183066.09239.b6. View

16.

Rooney Riggs E, Andersen E, Cherry A, Kantarci S, Kearney H, Patel A . Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2019; 22(2):245-257. PMC: 7313390. DOI: 10.1038/s41436-019-0686-8. View

17.

Carss K, Hillman S, Parthiban V, McMullan D, Maher E, Kilby M . Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound. Hum Mol Genet. 2014; 23(12):3269-77. PMC: 4030780. DOI: 10.1093/hmg/ddu038. View

18.

de Leon Reyes N, Bragg-Gonzalo L, Nieto M . Development and plasticity of the corpus callosum. Development. 2020; 147(18). DOI: 10.1242/dev.189738. View

19.

Glass H, Shaw G, Ma C, Sherr E . Agenesis of the corpus callosum in California 1983-2003: a population-based study. Am J Med Genet A. 2008; 146A(19):2495-500. PMC: 2574703. DOI: 10.1002/ajmg.a.32418. View

20.

Weissbach T, Massarwa A, Hadi E, Lev S, Haimov A, Katorza E . Early Fetal Corpus Callosum: Demonstrating Normal Growth and Detecting Pathologies in Early Pregnancy. AJNR Am J Neuroradiol. 2023; 44(2):199-204. PMC: 9891336. DOI: 10.3174/ajnr.A7757. View