Diamynova K. S., Yena M. S., Zhukova D. A., Nikolenko D. Ye, Hryn V. H.

MOLECULAR GENETIC ASPECTS OF THE FORMATION OF CONJOINED TWINS

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Diamynova K. S., Yena M. S., Zhukova D. A., Nikolenko D. Ye, Hryn V. H.

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LITERATURE REVIEWS

Type of article:

Scientific article

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Conjoined (Siamese) twins represent a rare anomaly of human embryonic development that arises during the early development of monozygotic twins and is characterized by varying degrees of anatomical union between the embryos. Despite extensive investigation of this phenomenon, the precise cellular and molecular mechanisms underlying its development remain incompletely understood. Current evidence from embryology, developmental genetics, and molecular biology suggests that disturbances in the spatiotemporal regulation of early embryogenesis, axial patterning, cell migration, and intercellular interactions may represent important components of its pathogenesis. The aim of this study was to summarize and critically analyze current scientific evidence on the embryological, molecular genetic, and epigenetic mechanisms involved in the formation of conjoined twins, with particular emphasis on the Wnt, BMP, and Hedgehog signaling pathways and their roles in body-axis establishment and embryonic morphogenesis. The methodological basis of the study was a systematic analysis of scientific publications in embryology, developmental genetics, molecular biology, and clinical medicine. Findings from embryological, pathomorphological, histological, genetic, molecular, and clinical studies were analyzed. The literature indicates that the formation of conjoined twins is associated with disturbances in the early development of monozygotic twins during the formation and organization of the embryonic disc. Traditionally, this process has been attributed to late and incomplete embryonic separation, although alternative models of morphogenesis remain under scientific discussion. The Wnt, BMP, and Hedgehog signaling pathways are key regulators of gastrulation, body-axis establishment, cell differentiation, and the spatial organization of tissues; therefore, disruption of their spatiotemporal activity is considered a potential molecular mechanism underlying abnormal embryonic patterning. Available molecular genetic evidence has not identified a single recurrent pathogenic mutation specific to conjoined twinning, highlighting the need for further investigation of gene-expression regulation, epigenetic mechanisms, and intercellular signaling interactions during early embryogenesis. The synthesis of current evidence advances our understanding of the biological mechanisms underlying conjoined twinning and highlights the potential of genomic, epigenomic, transcriptomic, and spatial molecular technologies for further investigation of this rare developmental anomaly.

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Bibliography:

1. Spencer R. Theoretical and analytical embryology of conjoined twins: Part I: Embryogenesis. Clin Anat. 2000;13(1):36-53. DOI: https://doi.org/10.1002/(sici)1098-2353(2000)13:1%3C36::aid-ca5%3E3.0.co;2-3
2. Sadler TW. Langman’s Medical Embryology. 14th ed. Philadelphia: Wolters Kluwer; 2019. 432 p.
3. Barresi MJF, Gilbert SF. Developmental Biology. 12th ed. New York: Oxford University Press; 2020. 758 p.
4. Spencer R. Conjoined Twins: Developmental Malformations and Clinical Implications. Baltimore: Johns Hopkins University Press; 2003. 476 p.
5. Mutchinick OM, Luna-Muñoz L, Amar E, Bakker MK, Clementi M, Cocchi G, et al. Conjoined twins: a worldwide collaborative epidemiological study of the International Clearinghouse for Birth Defects Surveillance and Research. Am J Med Genet C Semin Med Genet. 2011;157C(4):274-287. DOI: https://doi.org/10.1002/ajmg.c.30321
6. O’Neill JA Jr, Holcomb GW 3rd, Schnaufer L, Templeton JM Jr, Bishop HC, Ross AJ 3rd, et al. Surgical experience with thirteen conjoined twins. Ann Surg. 1988;208(3):299-312. DOI: https://doi.org/10.1097/00000658-198809000-00007
7. O’Connell JEA. Craniopagus twins: surgical anatomy and embryology and their implications. J Neurol Neurosurg Psychiatry. 1976;39(1):1-22. DOI: https://doi.org/10.1136/jnnp.39.1.1
8. Chen Y, Chen W, Wang Y, Wei Y, Huang J. Integrated multiomics reveal the molecular characteristics of conjoined twin fetuses. Reprod Biomed Online. 2023;47(1):26-34. DOI: https://doi.org/10.1016/j.rbmo.2023.03.001
9. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005;102(30):10604-10609. DOI: https://doi.org/10.1073/pnas.0500398102
10. Oostra RJ, Schepens-Franke AN, Magno G, Zanatta A, Boer LL. Conjoined twins and conjoined triplets: at the heart of the matter. Birth Defects Res. 2022;114(12):596-610. DOI: https://doi.org/10.1002/bdr2.2066
11. Boer LL, Schepens-Franke AN, Winter E, Oostra RJ. Characterizing the coalescence area of conjoined twins to elucidate congenital disorders in singletons. Clin Anat. 2021;34(6):845-858. DOI: https://doi.org/10.1002/ca.23725
12. Stone JL, Goodrich JT. The craniopagus malformation: classification and implications for surgical separation. Brain. 2006;129(Pt 5):1084-1095. DOI: https://doi.org/10.1093/brain/awl065
13. Arnold SJ, Robertson EJ. Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo. Nat Rev Mol Cell Biol. 2009;10(2):91-103. DOI: https://doi.org/10.1038/nrm2618
14. Zinski J, Tajer B, Mullins MC. TGF-β family signaling in early vertebrate development. Cold Spring Harb Perspect Biol. 2018;10(6):a033274. DOI: https://doi.org/10.1101/cshperspect.a033274
15. Shi DL. Canonical and non-canonical Wnt signaling generates molecular and cellular asymmetries to establish embryonic axes. J Dev Biol. 2024;12(3):20. DOI: https://doi.org/10.3390/jdb12030020
16. Hill CS. Establishment and interpretation of NODAL and BMP signaling gradients in early vertebrate development. Curr Top Dev Biol. 2022;149:311-340. DOI: https://doi.org/10.1016/bs.ctdb.2021.12.002
17. Jiang J, Hui CC. Hedgehog signaling in development and cancer. Dev Cell. 2008;15(6):801-812. DOI: https://doi.org/10.1016/j.devcel.2008.11.010
18. Abas R, Othman I, Naidu R. Gastrulation and body axes formation: a molecular concept and its clinical correlates. Malays J Med Sci. 2022;29(6):4-17. DOI: https://doi.org/10.21315/mjms2022.29.6.2
19. Castro P, Werner H, Matos AP, Ribeiro G, Lopes J, Araujo Júnior E. Antenatal diagnosis of parapagus conjoined twins: 3D virtual and 3D physical models. Rev Bras Ginecol Obstet. 2021;43(12):985-987. DOI: https://doi.org/10.1055/s-0041-1739297
20. Karn M, Mahato B, Sah P, Basnet A, Yonghang S, Pandit C. Dicephalus parapagus conjoined twins. Clin Case Rep. 2021;9:e04663. DOI: https://doi.org/10.1002/ccr3.4663
21. Kusmayadi DD, Emiliana L, Trifosa SC. Characteristics and management of conjoined twins: a single-centre retrospective descriptive study. Med J Malaysia. 2024;79(Suppl 4):17–22.
22. Xiao J, Liao K, Tan Z, Xie J, Lai H, Zhang S, et al. The application value of prenatal ultrasound in conjoined twins. J Clin Ultrasound. 2025;53(1):122–128. DOI: https://doi.org/10.1002/jcu.23851
23. Shafarenko MS, Zuker RM. Conjoined twins. Clin Plast Surg. 2025;52(2):301-310. DOI: https://doi.org/10.1016/j.cps.2024.08.007
24. Collins RT II, O’Connor MJ. The outcomes of surgical separation in thoracopagus twins with conjoined hearts: an analysis of the literature. Pediatr Cardiol. 2021;42(4):875-882. DOI: https://doi.org/10.1007/s00246-021-02555-8
25. Spencer R. Anatomic description of conjoined twins: a plea for standardized terminology. J Pediatr Surg. 1996;31(7):941-944. DOI: https://doi.org/10.1016/S0022-3468(96)90417-0

Publication of the article:

«Bulletin of problems biology and medicine», 2026 Issue 3, 182, 46-53 pages, index UDC 611.013:575.1:618.39-007.26

DOI:

10.29254/2077-4214-2026-3-182-46-53