Keywords
Chromosomal Alterations
Pregnancy
How to Cite
Abstract
Miscarriage can be associated with a variety of genetic factors, hematological disorders, including changes in the anatomy of the uterus. Furthermore, there is a relationship between maternal age and reproductive health.Epidemiological studies reveal high rates of subfertility and spontaneous abortions linked to a range of these factors. Therefore, this study aims to investigate the genetic factors associated with pregnancy loss and promote the dissemination of results in a language accessible to the population, through a podcast channel with the aim of increasing awareness and facilitating access to appropriate health services. The study was performed through a narrative literature review. The development of the podcast channel was performed through recordings in an audiovisual environment with scripts developed based on the research results. Cytogenetic abnormalities representing around 50% of fetal deaths in the first trimester and 6% to 13% of stillbirths. Among the main alterations are trisomies of chromosomes 13, 18, 16, 22 and monosomy of chromosome X. Mutations in genes related to the cell cycle are also related to pregnancy loss due to the fact that they trigger serious congenital and developmental defects in embryos. Furthermore, hematological changes, such as thrombophilia and antiphospholipid syndrome, are related to pregnancy loss. This research unveiled the complexity of genetic interactions in the context of miscarriage, emphasizing the urgent need for interdisciplinary collaborations. The identification of specific genetic markers holds the potential to enhance screening and therapeutic strategies, underscoring the importance and recognition of the interconnection between genetic factors and physiological events during pregnancy.
References
ALY, J.; KRUSZKA, P. Novel insights in Turner syndrome. Current Opinion in Pediatrics, 2022.
AOI, H. et al. Nonsense variants of STAG2 result in distinct congenital anomalies. Human Genome Variation. 2020.
ARAGÃO, R. et al. Revisão sistemática sobre trombofilia na gestação: profilaxia, diagnóstico laboratorial e tratamento. 2018.
ARASKEVI, M. et al. Psychiatrische Komorbidität beim Ullrich-Turner-Syndrom. Fortschritte Der Neurologie Psychiatrie, 2018.
ARMSTRONG, A., GAW, S., PLATT, L. Mosaic Trisomies 8, 9, and 16. Obstetric Imaging: Fetal Diagnosis and Care, 2018.
ARTAL-MITTELMARK, R. Concepção e desenvolvimento pré-natal. Disponível em: <https://www.msdmanuals.com/pt-br/profissional/ginecologia-e-obstetr%C3%ADcia/abordagem-%C3%A0-gestante-e-cuidados-pr%C3%A9-natais/concep%C3%A7%C3%A3o-e-desenvolvimento-pr%C3%A9-natal>. Acesso em: 13 set. 2023.
ASTNER, A., SCHWINGER, E., CALIEBE, A., et al. Sonographically detected fetal and placental abnormalities associated with trisomy 16 confined to the placenta. A case report and review of the literature. Prenat Diag, 1998.
BALASUNDARAM, P., AVULAKUNTA, I. Edwards Syndrome. 2023.
BERGSTRÖM, A. et al. Insights into human genetic variation and population history from 929 diverse genomes. Science, 2020.
BLUE, N.; PAGE, J.; SILVER, R. Genetic abnormalities and pregnancy loss. In: Seminars in perinatology. WB Saunders, 2019.
BREMM, J. et al. Genetic and in silico analysis show a role of SMAD3 on recurrent pregnancy loss. Human Fertility (Cambridge, England), 2022.
CAREY, J. Trisomy 18 And Trisomy 13 Syndromes. Cassidy and Allanson’s Management of Genetic Syndromes, 2020.
COLUCCI, G., TSAKIRIS, D. A. Thrombophilia Screening: Universal, Selected, or Neither. Clinical and Applied Thrombosis/Hemostasis, 2017.
CUI, X. et al. A basic understanding of Turner syndrome: Incidence, complications, diagnosis, and treatment. Intractable Rare Dis Res. 2018
DAI, C., FEI, Y., LI, J., SHI, Y., YANG, X. A Novel Review of Homocysteine and Pregnancy Complications. Biomed Res Int. 2021.
DIMITRIADIS, E. et al., Recurrent pregnancy loss. Nat Rev Dis Primers, 2020.
EDWARDS, H. et al. A new trisomic syndrome. Lancet, I960.
FAGUNDES, S. et al. Síndrome antifosfolipídica e morbidade gestacional. 2005.
FARLAND, L. et al., Endometriosis and Risk of Adverse Pregnancy Outcomes. Obstet Gynecol, 2019.
FIGUEIRÓ, E. et al. Marcadores séricos de trombofilias hereditárias e anticorpos antifosfolípides em gestantes com antecedentes de pré-eclâmpsia grave. Revista Brasileira de Ginecologia e Obstetrícia, 2012.
FRANCISCO, C. et al. Os fatores genéticos na perda gestacional. Artigo de Revisão, 2013.
GOULART, V. Óbito fetal em gestações únicas com diagnóstico de trissomias dos cromossomos 21, 18, 13 e monossomia do X. 2014.
GRAVHOLT, C. H. et al. The changing face of Turner syndrome. Endocrine Reviews, 2022.
GU, C. et al. Chromosomal Aneuploidy Associated With Clinical Characteristics of Pregnancy Loss. Frontiers in Genetics, 2021.
HEGNER, C. et al. Diagnóstico tardio de síndrome de DiGeorge em criança hipocalcêmica: relato de caso. Rev. méd, 2016.
HEINRICH, T., et al., Live-born trisomy 22: patient report and review. Molecular syndromology, 2013.
HELENO, S. Fatores Genéticos e Cromossomais na Perda Gestacional. Universidade do porto | Instituto de ciências biomédicas Abel Salazar, 2014.
HOOK, E., WARBURTON, D. Turner syndrome revisited: review of new data supports the hypothesis that all viable 45,X cases are cryptic mosaics with a rescue cell line, implying an original by mitotic loss. Hum Genet. 2014.
JASLOW, Carolyn R.et al.Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertility and sterility, v. 93, n. 4, p. 1234-1243, 2010.
KROES, I. JANSSENS, S. DEFOORT, P. Ultrasound features in trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) in a consecutive series of 47 cases. Facts Views Vis Obgyn, 2014.
KONINCK et al. Essential Roles of Cohesin STAG2 in Mouse Embryonic Development and Adult Tissue Homeostasis. Cell Reports, 2020.
LAING, A., LOWELL, S., BRICKMAN, J. Gro/TLE enables embryonic stem cell differentiation by repressing pluripotent gene expression. Developmental Biology, 2015.
LAISK, T. et al. The genetic architecture of sporadic and multiple consecutive miscarriage. Nature Communications, 2020.
LAUS, A. et al. Karyotype/phenotype correlation in partial trisomies of the long arm of chromosome 16: Case report and review of literature. American Journal of Medical Genetics, 2012.
LUIZ, A. et al., TRISSOMIA EM MOSAICO DO CROMOSSOMO 22 E INVERSÃO DO CROMOSSOMO 9: UM RELATO DE CASO. In: II SIBRAGEN - Simpósio Brasileiro de Genética - On-Line , 2021.
MATTAR, R., TRAINÁ, E., DAHER, S. Limites na investigação imunológica e genética em aborto recorrente. Revista Brasileira de Ginecologia e Obstetrícia, 2015.
MCNICOLL, F., STEVENSE, M., JESSBERGER, R. Cohesin in Gametogenesis. Current Topics in Developmental Biology, 2013.
MEINHARDT, G. et al. Wnt-Dependent T-Cell Factor-4 Controls Human Etravillous Trophoblast Motility. Endocrinology, 2014.
MENCHERO, S. et al. Transitions in cell potency during early mouse development are driven by Notch. eLife, 2019.
MORA, A. et al. Anomalías CromosómIicas en Abortos espontáneos. Rev Peru Ginecol Obstet, 2016.
MULLEGAMA, S. et al. De novo loss‐of‐function variants in STAG2 are associated with developmental delay, microcephaly, and congenital anomalies. American Journal of Medical Genetics Part A, 2017.
MULLEGAMA, S. et al. Mutations in STAG2 cause an X-linked cohesinopathy associated with undergrowth, developmental delay, and dysmorphia: Expanding the phenotype in males. Molecular Genetics & Genomic Medicine, 2018.
NGUYEN, Hoang H. et al. Mosaic Trisomy 16 Associated with Left Lung Agenesis, Abnormal Left Arm, and Right Pulmonary Artery Stenosis: Expanding the Phenotype and Review of the Literature. Journal of Pediatric Genetics, v. 11, n. 04, p. 324-332, 2020.
OMIM. OMIM - Online Mendelian Inheritance in Man. Disponível em: https://www.omim.org/, 2023.
PAGE, J.; SILVER, R. Genetic causes of recurrent pregnancy loss. Clinical obstetrics and gynecology, 2016.
PATAU, K, et al., Multiple congenital anomaly caused by an extra chromosome. Lancet 1960.
PEROOS, S. et al. Longevity and Patau syndrome: what determines survival? Case Reports, 2012.
PETRY, P. et al. Clinical features and prognosis of a sample of patients with trisomy 13 (Patau syndrome) from Brazil. American Journal of Medical Genetics Part A, 2013.
RAGUEMA, N et al. FAS A-670G and Fas ligand IVS2nt A 124G polymorphisms are significantly increased in women with pre-eclampsia and may contribute to HELLP syndrome: a case-controlled study. Bjog: An International Journal Of Obstetrics And Gynaecology, 2018.
ROBERTS, A., et al. Noonan syndrome. Lancet, 2013.
ROSA, R. et al. Trissomia 18: revisão dos aspectos clínicos, etiológicos, prognósticos e éticos. Revista Paulista de Pediatria, 2013.
ROSA, R. et al. Características clínicas de uma amostra de pacientes com a síndrome do olho do gato. Revista da Associação Médica Brasileira, 2010a.
ROSA, R. et al. Variabilidade fenotípica na síndrome do cromossomo supernumerário der(22)t(11;22) (síndrome de Emanuel). Revista Paulista de Pediatria. 2010b.
SÁNCHEZ, J. et al. Severe fetal malformations associated with trisomy 16 confined to the placenta. Prenat Diagn, 1997.
SANTOS, F., JESUS, N. Acompanhamento da síndrome antifosfolipídeo (SAF) obstétrica. Revista Hospital Universitário Pedro Ernesto, 2015.
SCHWARTZ, S. Molecular Cytogenetics and Prenatal Diagnosis, 2015.
SHANKAR, N., NAGALLI, S. Turner Syndrome, 2023.
SPARKS, T., THAO, K., NORTON, M. Mosaic trisomy 16: what are the obstetric and long-term childhood outcomes?, 2017.
SPRINGETT, A. et al. Congenital anomalies associated with trisomy 18 or trisomy 13: A registry-based study in 16 european countries, 2000-2011. American Journal of Medical Genetics Part A, 2015.
STRACHAN, T., READ, A. Human molecular genetics. Boca Raton, Fl Crc Press, Taylor & Francis Group, 2019.
SUGAYAMA, S., KIM, C. Anomalias autossômicas. In: CARAKUSHANSKY, G. Doenças genéticas em pediatria. Rio de Janeiro: Ed Guanabara Koogan, 2001.
TOLMACHEVA, E. N. et al. Identification of differentially methylated genes in first-trimester placentas with trisomy 16. Scientific Reports, v. 12, n. 1, p. 1166, 2022.
UEHARA, S., ROSA, G. Associação da deficiência de ácido fólico com alterações patológicas e estratégias para sua prevenção: uma visão crítica. Revista de Nutrição, 2010.
WATSON, W. et al. Sonographic Detection of Trisomy 13 in the First and Second Trimesters of Pregnancy, 2007.
WINK, D. et al., Síndrome de Edwards. Porto Alegre, 2001.
WOLFF, D, et al. Laboratory guideline for Turner syndrome. Genetics in Med. 2010.
ZHONG, Q. LAYMAN, L. Genetic considerations in the patient with Turner syndrome- 45,X with or without mosaicism. Fertil Steril, 2012.
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Copyright (c) 2023 Sarah Vitarelli Percegoni Vidal, Thais Tinum Santos, Patrícia Andrade Diniz, Larissa Castro Silva, Ayla Mel Gomes dos Santos, Aline de Jesus Souza, Simone de Souza Ventura, Lívia das Graças Amaral Avelar, Aline Aparecida Silva Martins