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

Polina N. Tsabai; Цабай Полина Николаевна; Irina S. Mukosey; Мукосей Ирина Сергеевна; Zalina K. Batyrova; Батырова Залина Кимовна; Nadezda S. Pavlova; Павлова Надежда Сергеевна; Zaira Kh. Kumykova; Кумыкова Заира Хасановна; Igor O. Sadelov; Саделов Игорь Олегович; Irina I. Kirillova; Кириллова Ирина Ильинична; Alexander A. Voskoboinikov; Воскобойников Александр Андреевич; Jekaterina Shubina; Шубина Екатерина; Elena V. Uvarova; Уварова Елена Витальевна

doi:10.18565/aig.2025.315

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

Authors: Tsabai P.N.¹, Mukosey I.S.¹, Batyrova Z.K.¹, Pavlova N.S.¹, Kumykova Z.K.¹, Sadelov I.O.¹, Kirillova I.I.¹, Voskoboinikov A.A.¹, Shubina J.¹, Uvarova E.V.¹
Affiliations:
1. Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Issue: No 12 (2025)
Pages: 112-119
Section: Original Articles
URL: https://journals.rcsi.science/0300-9092/article/view/367110
DOI: https://doi.org/10.18565/aig.2025.315
ID: 367110

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Abstract

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.