Two cases of 16p11.2 deletion syndrome in adolescent girls with genital malformations

DOI

https://dx.doi.org/10.18565/aig.2025.315

Tsabai P.N., Mukosey I.S., Batyrova Z.K., Pavlova N.S., Kumykova Z.Kh., Sadelov I.O., Kirillova I.I., Voskoboinikov A.A., Shubina J., Uvarova E.V.
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia

Background: Chromosome 16p11.2 deletion syndrome is a clinically heterogeneous condition characterized by impaired psychomotor development, obesity, and mental disorders. The disorder has an autosomal dominant inheritance pattern; however, due to incomplete penetrance and variable manifestations, microdeletion carriage often goes unnoticed. The frequency of 16p11.2 deletions among patients with developmental delays, autism spectrum disorders, schizophrenia, obesity, and genitourinary malformations is several times higher than in the general population. In Mayer–Rokitansky–Küster–Hauser syndrome, 16p11.2 microdeletions involving the TBX6 gene are a common genetic finding. Point variants in TBX6 gene have been described in Herlyn–Werner–Wunderlich syndrome.
Objective: To study the genetic causes of uterine and vaginal anomalies in two patients with the 16p11.2 microdeletion.
Materials and methods: Whole-exome sequencing with copy number variation analysis was performed in the patients. Patient G. also underwent chromosomal microarray analysis. Low-coverage genome sequencing was performed in the patients and their parents to determine the origin of the 16p11.2 deletion.
Results: A proximal 16p11.2 deletion was detected in patient E. with uterine and vaginal aplasia and in patient G. with Herlyn–Werner–Wunderlich syndrome. The patients had the following extragenital symptoms of the genetic disorder: thrombocytopenia, obesity, and skeletal anomalies were noted in patient E.; a delay in psychomotor development, renal aplasia, and skeletal anomalies were revealed in patient G.
Conclusion: These cases confirm the pleiotropic effects of the 16p11.2 deletion and the need for a multidisciplinary approach to patients with this genetic variant. Given the absence of pathognomonic features, differential diagnosis with this disease should be considered among patients with genitourinary anomalies, delayed psychomotor development, obesity, and hematological anomalies. Since these patients are reproductively capable, identifying the 16p11.2 microdeletion significantly impacts the risk assessment for congenital pathologies in their children and pregnancy planning strategies.

Authors’ contributions: Tsabai P.N., Mukosey I.S., Shubina J. – developing the concept and design of the study; Tsabai P.N., Batyrova Z.K., Kumykova Z.Kh. – consulting the patients, collecting and processing the material; Mukosey I.S., Sadelov I.O., Kirillova I.I., Voskoboinikov A.A. – bioinformatics analysis; Tsabai P.N., Mukosey I.S., Pavlova N.S., Batyrova Z.K. – writing the text; Shubina J., Uvarova E.V. – 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: This study was approved by the Ethics Committee (Minutes No. 07 of the meeting of the Biomedical Research Ethics Committee at the V.I. Kulakov National Medical Research Center of the Ministry of Health of Russia dated 21.08.2025).
Patient Consent for Publication: The patients and their parents provided an informed consent to the use of all information for scientific purposes.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Tsabai P.N., Mukosey I.S., Batyrova Z.K., Pavlova N.S., Kumykova Z.Kh., Sadelov I.O.,
Kirillova I.I., Voskoboinikov A.A., Shubina J., Uvarova E.V. Two cases of 16p11.2 deletion syndrome in
adolescent girls with genital malformations.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (12): 112-119 (in Russian)
https://dx.doi.org/10.18565/aig.2025.315

16p11.2 microdeletion

TBX6

whole-exome sequencing

chromosomal microarray analysis

genital malformations

Mayer–Rokitansky–Küster–Hauser syndrome

Herlyn–Werner–Wunderlich syndrome

OHVIRA

scoliosis

developmental delay

Full text (in Russian)

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Received 30.10.2025

Accepted 09.12.2025

Polina N. Tsabai, geneticist, MD, 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, Russian Federation, 117997, +7(916)940-22-06, polinatsabai@gmail.com,
https://orcid.org/0000-0001-5110-0827
Irina S. Mukosey, Researcher, 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, Russian Federation, 117997,
https://orcid.org/0000-0002-2225-8366
Zalina K. Batyrova, gynecologist, MD, PhD, 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, Russian Federation, 117997, linadoctor@mail.ru,
https://orcid.org/0000-0003-4997-6090
Nadezda S. Pavlova, Junior Researcher, 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, Russian Federation, 117997, pavnadser@gmail.com,
https://orcid.org/0000-0001-5619-2695
Zaira Kh. Kumykova, gynecologist, MD, PhD, 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, Russian Federation, 117997, zai-kumykova@yandex.ru, https://orcid.org/0000-0001-7511-1432
Igor O. Sadelov, geneticist, 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, Russian Federation, 117997, sadelovigor@gmail.com, https://orcid.org/0000-0001-5916-0672
Irina I. Kirillova, specialist, 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, Russian Federation, 117997,
https://orcid.org/0009-0008-2182-9631
Alexander A. Voskoboinikov, Junior Researcher, 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, Russian Federation, 117997,
https://orcid.org/0000-0002-4543-7156
Jekaterina Shubina, PhD, Head of 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, Russian Federation, 117997, e_shubina@oparina4.ru, https://orcid.org/0000-0003-4383-7428
Elena V. Uvarova, Dr. Med. Sci., Professor, Corresponding Member of RAS, 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, Russian Federation, 117997, elena-uvarova@yandex.ru, https://orcid.org/0000-0002-3105-5640
Corresponding author: Polina N. Tsabai, polinatsabai@gmail.com

Two cases of 16p11.2 deletion syndrome in adolescent girls with genital malformations

Tsabai P.N., Mukosey I.S., Batyrova Z.K., Pavlova N.S., Kumykova Z.Kh., Sadelov I.O., Kirillova I.I., Voskoboinikov A.A., Shubina J., Uvarova E.V.

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