TRANSLATIONAL AND CLINICAL MEDICINE - Georgian Medical Journal

Background

Structural anomalies of the X chromosome represent a significant cause of reproductive dysfunction and primary amenorrhea. The coexistence of large-scale deletion and duplication within the same X chromosome is rare and associated with marked clinical variability. In this context, spontaneous pubertal development represents an unusual and rarely reported finding. Advances in cytogenetic and molecular techniques, particularly chromosomal microarray analysis, have improved the detection of combined of chromosomal rearrangements and are essential for accurate diagnosis.

Case Presentation

We report a 16-year-old adolescent girl presenting with primary amenorrhea and spontaneous but incomplete pubertal development. Physical examination revealed height 152 cm, with minor dysmorphic features, including a low posterior hairline and high-arched palate. Tanner staging corresponded to B4P4Ax3Me0, with normal female external genitalia. Hormonal evaluation demonstrated hypergonadotropic hypogonadism with elevated FSH and LH and low estradiol levels. Pelvic ultrasound revealed a hypoplastic uterus and small ovaries without visible follicles.

Cytogenetic analysis identified a structural anomaly of the X chromosome (46,X,del(X)(q21)). Chromosomal microarray analysis confirmed a combined rearrangement consisting of a heterozygous ~70 Mb deletion at Xq21.2–q28 and a heterozygous ~51 Mb duplication at Xp22.33–p11.2. Despite the presence of a terminal Xq deletion, height delay was not observed, as the patient’s stature was consistent with familial height.

Conclusion

This case highlights the importance of integrated cytogenetic and molecular analysis in patients with DSD. Combined X chromosome copy number variations can result in diverse clinical phenotypes, requiring careful genetic counseling, evaluation of X chromosome inactivation, and multidisciplinary management. Early diagnosis and comprehensive care may improve outcomes, while ongoing advances in genetic research will further refine understanding and guide targeted diagnostic strategies.

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