Genital anomalies in patients with trichorhinophalangeal syndrome

DOI

https://dx.doi.org/10.18565/aig.2025.286

Tsabai P.N., Rogacheva M.S., Batyrova Z.K., Lapshina A.M., Uvarova E.V., Shubina J., Trofimov D.Yu.
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia

Background: Congenital malformations of the genital organs represent a range of anatomical variants leading to dysfunction due to complete or partial organ obstruction. Genetic causes of reproductive tract anomalies include chromosomal and monogenic disorders, as well as syndromic ones. Trichorhinophalangeal syndrome (TRFS) is a rare autosomal dominant disease characterized by craniofacial and skeletal anomalies.
Objective: To study the genetic causes of a vaginal malformation in a patient with TRPS and to review cases of genital anomalies in patients with TRPS.
Case report: A 12-year patient was admitted for surgical correction of a genital anomaly, namely distal vaginal atresia. Shortened limbs, brachydactyly, and slow growth were noted from an early age. The patient underwent whole-exome sequencing, and her parents were examined using Sanger sequencing. The patient was found to have a pathogenic heterozygous variant in the TRPS1 gene, resulting in an amino acid substitution at position 932 of the protein (NM_014112.5: c.2795C>T, p.Ala932Val). The variant was not detected in the parents; it arose de novo. This case is the only molecularly confirmed case of TRPS type 3 with vaginal malformations and the second description of the syndrome in the Russian scientific literature. Female reproductive system defects are not among the classic features of TRPS; however, we found isolated reports of genital anomalies in patients of both sexes.
Conclusion: Our observation confirms that genital anomalies are a part of the phenotypic spectrum of TRPS. We highlight the need for gynecological examination of all adolescent girls diagnosed with TRPS to ensure early detection of genital malformations.

Authors’ contributions: Uvarova E.V., Trofimov D.Yu. – developing the concept and design of the study; Tsabai P.N., Batyrova Z.K., Lapshina A.M. – consulting the patients, collecting and processing the material; Rogacheva M.S., Shubina J. – bioinformatics analysis; Tsabai P.N., Rogacheva M.S., Shubina J. – writing the text; Shubina J., Batyrova Z.K. – editing the article.
Conflicts of interest: Authors declare lack of the possible conflicts of interest.
Funding: This work was supported by the Russian Science Foundation, Grant No. 25-65-00040.
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 (Protocol No. 7 of the meeting of the Ethics Commission for Biomedical Research, dated August 21, 2025).
Patient Consent to Publication: The patient and her parents provided an informed consent to the use of all information including photos for scientific purposes.
For citation: Tsabai P.N., Rogacheva M.S., Batyrova Z.K., Lapshina A.M., Uvarova E.V., Shubina J.,
Trofimov D.Yu. Genital anomalies in patients with trichorhinophalangeal syndrome.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (1): 120-129 (in Russian)
https://dx.doi.org/10.18565/aig.2025.286

trichorhinophalangeal syndrome

TRPS1

whole-exome sequencing

genital anomalies

vaginal atresia

short stature

Full text (in Russian)

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Received 09.10.2025

Accepted 29.12.2025

Polina N. Tsabai, geneticist, M.D., Department of Clinical Genetics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, 4, Ac. Oparina str., Moscow, Russia, 117997, +7(916)940-22-06, polinatsabai@gmail.com, https://orcid.org/0000-0001-5110-0827
Margarita S. Rogacheva, Junior Researcher, Genomic Data Analysis Laboratory, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, 4, Ac. Oparina str., Moscow, Russia, 117997, m_rogacheva@oparina4.ru, https://orcid.org/0000-0002-2495-2554
Zalina K. Batyrova, gynecologist, M.D., Department of Children and Adolescent Gynecology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, 4, Ac. Oparina str., Moscow, Russia, 117997, linadoctor@mail.ru,
https://orcid.org/0000-0003-4997-6090
Anna M. Lapshina, geneticist, M.D., Department of Clinical Genetics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, 4, Ac. Oparina str., Moscow, Russia, 117997, a_lapshina@oparina4.ru, https://orcid.org/0009-0002-6408-5747
Elena V. Uvarova, Dr. Med. Sci., Professor, Head of Department of Pediatric and Adolescent Gynecology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, 4, Ac. Oparina str., Moscow, Russia, 117997, elena-uvarova@yandex.ru,
https://orcid.org/0000-0002-3105-5640
Jekaterina Shubina, PhD, Head of 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 the Russian Federation, 4, Ac. Oparina str., Moscow, Russia, 117997, e_shubina@oparina4.ru,
https://orcid.org/0000-0003-4383-7428
Dmitry Yu. Trofimov, Dr. Bio. Sci., Corresponding Member of the RAS, Director of Institute of Reproductive Genetics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, 4, Ac. Oparina str., Moscow, Russia, 117997, molgen@bk.ru,
https://orcid.org/0000-0002-1569-8486.
Corresponding author: Polina N. Tsabai, polinatsabai@gmail.com

Genital anomalies in patients with trichorhinophalangeal syndrome

Tsabai P.N., Rogacheva M.S., Batyrova Z.K., Lapshina A.M., Uvarova E.V., Shubina J., Trofimov D.Yu.

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