Monozygotic twins discordant for multiple congenital anomalies

DOI

https://dx.doi.org/10.18565/aig.2023.286

Bolshakova A.S., Yarygina T.A., Sakalo V.A., Gladkova K.A., Barkov I.Yu., Sadelov I.O., Khodzhaeva Z.S.
1) Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia; 2) A.N. Bakulev National Medical Research Center for Cardiovascular Surgery, Ministry of Health of Russia, Moscow, Russia; 3) Peoples’ Friendship University of Russia, Moscow, Russia

Relevance: The management of a monochorionic multiple pregnancy with abnormal development of one of the fetuses is a clinical and ethical dilemma, since, there is a risk of preterm birth and perinatal death of the second twin regardless of the chosen tactics. Modern molecular genetic methods assist in optimizing the management of pregnant women and newborns in such cases.
We present a case report on the management of multiple pregnancy: discordant monozygotic twins with multiple developmental anomalies.
Case report: A 40-year-old multigravida presented at 17 weeks gestation to the National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Moscow, to determine the tactics of managing monochorionic twins with large omphalocele and spinal deformity in one of the fetuses.
At the first stage of the examination, the patient underwent a separate amniocentesis; normal female molecular karyotype arr(1-22,X)x2 was detected in both fetuses. Impairments in methylation of IC1 (H19) and IC2 (KCNQ1OT1) sites of the critical region of chromosome 11 associated with Beckwith–Wiedemann syndrome were excluded on the basis of DNA of the amniotic fluid in both fetuses. Monozygosity was confirmed by matching samples of the first and second fetuses for five SNP markers on each of 22 pairs of autosomes. Given the normal result of the genetic examination of both fetuses and the potential risks of perinatal complications during intrauterine intervention, the patient refused selective fetocide.
An operative delivery was performed at 33 weeks and 5 days due to the repeated increase in polyhydramnios and zero diastolic blood flow in the umbilical cord arteries, according to the ultrasound Doppler assessment. The first healthy girl was born with a body weight of 2140 g, an Apgar score of 7-8 points, and was discharged home in satisfactory condition at the age of 12 days of life. The second girl with multiple developmental anomalies was born with a body weight of 1760 g, an Apgar score of 5-6 points, and died at the age of 2 days 2 hours due to multiple organ failure.
Both children had a normal female karyotype (46,XX) which was revealed postnatally, and a whole-exome sequencing of pathogenic and likely pathogenic variants associated with the phenotype was performed. Monozygosity of the twins was confirmed, no accidental findings were detected.
Conclusion: The above case demonstrates the principles of modern ante- and perinatal multidisciplinary tactics for multiple pregnancies discordant for structural fetal malformations.

Authors’ contributions: Khodzhaeva Z.S., Sakalo V.A., Bolshakova A.S., Yarygina T.A. – developing the concept of the study; Sakalo V.A., Gladkova K.A., Bolshakova A.S., Barkov I.Yu. – collecting and processing the material; Bolshakova A.S., Yarygina T.A., Sakalo V.A. – writing the text; Khodzhaeva Z.S., Sadelov I.A. – editing the text.
Conflicts of interest: Authors declare lack of the possible conflicts of interests.
Funding: The investigation has been supported by the Russian Foundation for Basic Research within the framework of Research Project № 121040600434-3.
Ethical Approval: The study was approved by the Ethical Review Board of the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
Patient Consent for Publication: The patient signed an informed consent to have genetic studies during pregnancy, consent to the examination of children and the publication of this clinical observation.
For citation: Bolshakova A.S., Yarygina T.A., Sakalo V.A., Gladkova K.A., Barkov I.Yu., Sadelov I.O., Khodzhaeva Z.S. Monozygotic twins discordant for multiple congenital anomalies.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (12): 205-212 (in Russian)
https://dx.doi.org/10.18565/aig.2023.286

monochorionic pregnancy

monozygotic twins

discordance

malformations

omphalocele

zygosity

selective fetocide

chromosomal microarray analysis (CMA)

whole-exome sequencing

Full text (in Russian)

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Received 08.12.2022

Accepted 11.12.2022

Anna S. Bolshakova, geneticist of the Department of Clinical Genetics, Institute of Reproductive Genetics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, +7(909)982-27-99, a_bolshakova@oparina4.ru, https://orcid.org/0000-0002-7508-0899,
117997, Russia, Moscow, Ac. Oparin str., 4.
Tamara A. Yarygina, MD, PhD, specialist of ultrasound diagnostics, researcher, Perinatal Cardiology Center, A.N. Bakulev National Medical Research Center of Cardiovascular Surgery, 121552, Russia, Moscow, Roublyevskoe Shosse, 135, +7(495)414-78-75; Associate Professor of the Department of Ultrasound Diagnostics of the Faculty of Continuing Medical Education of the Medical Institute, Peoples’ Friendship University of Russia named after Patrice Lumumba, 127015, Russia, Moscow, Pistsovaya str., 10, tamarayarygina@gmail.com, https://orcid.org/0000-0001-6140-1930
Viktoriya A. Sakalo, MD, PhD, junior researcher of the Department of Pregnancy Pathology, Institute of Obstetrics, doctor of the 1st Obstetric Department of Pregnancy Pathology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, +7(929)588-72-08,
v_sakalo@oparina4.ru, https://orcid.org/0000-0002-5870-4655, 117997, Russia, Moscow, 117997, Russia, Moscow, Ac. Oparin str., 4.
Kristina A. Gladkova, MD, PhD, senior researcher of the Fetal Medicine Unit, Institute of Obstetrics, Head of the 1st Obstetric Department of Pregnancy Pathology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, +7(916)321-10-07,
k_gladkova@oparina4.ru, https://orcid.org/0000-0001-8131-4682, 117997, Russia, Moscow, Ac. Oparin str., 4.
Ilya Yu. Barkov, MD, PhD, Head of the Laboratory of Prenatal DNA Screening, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, +7(495)438-24-10, i_barkov@oparina4.ru, 117997, Russia, Moscow, Ac. Oparin str., 4.
Igor O. Sadelov, MD, geneticist, Laboratory of Genomic Data Analysis, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, +7(495)438-24-10, a_sadelov@oparina4.ru, 117997, Russia, Moscow, Ac. Oparin str., 4.
Zulfiya S. Khodzhaeva, Dr. Med. Sci., Professor, Deputy Director of Obstetrics Institute, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, +7(495)438-07-88, z_khodzhaeva@oparina4.ru, https://orcid.org/0000-0001-8159-3714,
117997, Russia, Moscow, Ac. Oparin str., 4.
Corresponding author: Anna S. Bolshakova, a_bolshakova@oparina4.ru

Monozygotic twins discordant for multiple congenital anomalies

Bolshakova A.S., Yarygina T.A., Sakalo V.A., Gladkova K.A., Barkov I.Yu., Sadelov I.O., Khodzhaeva Z.S.

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