Trichohepatoenteric syndrome in the fetus: first described variants in the SKIC2 gene
Sidorchuk M.A., Karetnikova N.A., Kostyukov K.V., Sadelov I.O., Trofimov D.Yu.
Objective. To present a clinical case of trichohepatoenteric syndrome (THES) in a fetus associated with new variants in the SKIC2 gene; to demonstrate the diagnostic value of whole exome sequencing (WES) in early fetal growth restriction (FGR) and to show the importance of timely medical genetic counseling (MGC).
Materials and methods. A clinical case of pregnancy in a 32-year-old woman with isolated decreased PAPP-A levels based on early prenatal screening (EPS) and FGR is presented. A dynamic examination was performed: non-invasive fetal ultrasound, non-invasive DNA screening (NIPS), and invasive chromosomal microarray analysis and whole exome sequencing (WES) of amniotic fluid.
Results. Two heterozygous undescribed pathogenic variants in the SKIC2 gene were detected during whole-exome sequencing of amniotic fluid in a patient with a low risk of trisomies 21, 18, 13 in the fetus according to EPS in the Astraia program and NIPS, with a normal molecular karyotype according to the results of the amniotic fluid examination of the fetus: (6_31967096-T-G), leading to the appearance of a site of premature translation termination and disruption of the synthesis of the full-length protein (p.Tyr811Ter, NM_006929), and a heterozygous variant of the nucleotide sequence (6-31967103-TG-T), leading to a shift in the reading frame and disruption of the synthesis of the full-length protein (p.Glu816ArgfsTer3, NM_006929, rs 768446878), associated with trichohepatoenteric syndrome (OMIM: 614602). The fetus was found to have a complex of previously undescribed prenatal features of THES, including congenital heart defects, nasal bone hypoplasia, pelvic kidney dystopia, and oligohydramnios.
Conclusion. A fetal phenotype with THES, caused by newly identified variants in the SKIC2 gene, is described. The importance of timely MGC in cases of extremely low PAPP-A and early FGR in the absence of chromosomal abnormalities is emphasized.
Authors' contributions. Trofimov D.Yu. – general supervision; Karetnikova N.A. – study concept and design, manuscript editing; Sidorchuk M.A. – material collection and processing, medical genetic counseling; Kostyukov K.V. – manuscript editing, fetal ultrasound scan; Sadelov I.O. – prenatal molecular genetic tests.
Conflicts of interest. The authors declare no conflicts of interest.
Funding. The study had no sponsorship support.
Patient Consent for Publication. The patient signed informed consent for the publication of her data.
For citation: Sidorchuk M.A., Karetnikova N.A., Kostyukov K.V., Sadelov I.O., Trofimov D.Yu.
Trichohepatoenteric syndrome in the fetus: first described variants in the SKIC2 gene.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (9): 170-174 (in Russian)
https://dx.doi.org/10.18565/aig.2026.54
Keywords
trichohepatoenteric syndrome (THES)
SKIC2
fetal growth restriction
early prenatal screening
PAPP-A
whole exome sequencing
medical genetic counseling
References
- Fabre A., Bourgeois P., Chaix C., Bertaux K., Goulet O., Badens Ch. Trichohepatoenteric syndrome. 2018. In: Adam M.P., Bick S., Mirzaa G.M., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington; 1993-2026.
- Mainas A., Maina A., Ziogas N., Papoulidis I., Athanasiadis A. Mid‑trimester ultrasound findings in tricho‑hepato‑enteric syndrome: a case report. Biomed. Rep. 2025; 23(1): 110. https://dx.doi.org/10.3892/br.2025.1988
- Zhou H., Fu F., Wang Y., Li R., Li Y., Cheng K. et al. Genetic causes of isolated and severe fetal growth restriction in normal chromosomal microarray analysis. Int. J. Gynecol. Obstet. 2023; 161(3): 1004-11. https://dx.doi.org/10.1002/ijgo.14620
- Meler E., Sisterna S., Borrell A. Genetic syndromes associated with isolated fetal growth restriction. Prenat. Diagn. 2020; 40(4): 432-46. https://dx.doi.org/10.1002/pd.5635
- Patil M., Panchanadikar T.M., Wagh G. Variation of PAPP-A level in the first trimester of pregnancy and its clinical outcome. J. Obstet. Gynaecol. India. 2014; 64(2): 116-9. https://dx.doi.org/10.1007/s13224-013-0481-4
- Filges I., Röthlisberger B., Boesch N. et al. Whole-exome sequencing for diagnosis of Peters-plus syndrome with variable severity. Mol. Syndromol. 2020; 11(5-6): 270-6. https://dx.doi.org/10.3233/NPM-1854
- Aoi H., Mizuguchi T., Suzuki T., Makino S., Yamamoto Y., Takeda S. et al. Whole exome sequencing of fetal structural anomalies detected by ultrasonography. J. Hum. Genet. 2021; 66(5): 499-507. https://dx.doi.org/10.1038/s10038-020-00869-8
- Chitty L.S., Mason S., Barrett A.N., McKay F., Lench N., Daley R. et al. Promises, pitfalls and practicalities of prenatal whole exome sequencing. Prenat. Diagn. 2018; 38(1): 10-9. https://dx.doi.org/10.1002/pd.5102
Received 11.02.2026
Accepted 15.05.2026
About the Authors
Mariia A. Sidorchuk, Geneticist at 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, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(977)447-03-73, m_sidorchuk@oparina4.ru,https://orcid.org/0009-0008-1373-7905
Natalia A. Karetnikova, Dr. Med. Sci., Obstetrician-Gynecologist, Geneticist, Chief Researcher at 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, 117997, Russia, Moscow,
Ac. Oparin str., 4, +7(495)438-24-10, n_karetnikova@oparina4.ru, https://orcid.org/0000-0002-5060-8239
Kirill V. Kostyukov, Dr. Med. Sci., Head of the Department of Functional and Ultrasound Diagnostics, Department of Visual Diagnostics, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(495)438-25-29,
k_kostyukov@oparina4.ru, https://orcid.org/0000-0003-3094-4013
Igor O. Sadelov, Geneticist at the Laboratory of Genomic Data Analysis, Institute of Reproductive Genetics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(495)438-24-10, i_sadelov@oparina4.ru,
https://orcid.org/0000-0002-5144-6307
Dmitry Yu. Trofimov, Corresponding Member of the Russian Academy of Sciences, Professor, Dr. Bio. Sci., Director of the Institute of Reproductive Genetics, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(495)438-49-51, d_trofimov@oparina4.ru, https://orcid.org/0000-0002-1569-8486
Сorresponding author: Mariia A. Sidorchuk, m_sidorchuk@oparina4.ru
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