MON-141 - Hormone Replacement Therapy in Turner Syndrome Caused by Xp11.2 Deletion: Clinical Implications of A Rare Cytogenetic Variant

Background
This abstract describes an exceptionally rare case of Turner syndrome caused by a proximal Xp11.2 deletion involving the SHOX (short stature homeobox-containing) gene. Turner syndrome affects approximately 1 in 2,000 females and results from complete or partial absence of one sex chromosome. Monosomy X (45,X) accounts for 40–50% of cases, followed by mosaicism, isochromosome Xq, and other structural abnormalities of the X chromosome. Rare etiologies, including proximal Xp deletions [46,XX,del(Xp11)], represent fewer than 6% of cases and are seldom reported. This case expands the phenotypic and genotypic spectrum of Turner syndrome and underscores the clinical relevance of rare SHOX-associated Xp deletions and their therapeutic implications.

Case Presentation
We report a 27-year-old woman with Turner syndrome caused by a rare proximal deletion of the short arm of the X chromosome [46,X,del(Xp11.2)], a genotype representing fewer than 6% of Turner syndrome cases. She was diagnosed at age 12 after evaluation for short stature and delayed puberty. Cytogenetic analysis revealed one normal X chromosome and one X chromosome with deletion of Xp at band p11.2, a region critical for ovarian development and SHOX gene expression. Pubertal induction at age 12 with estrogen and progesterone resulted in partial pubertal development and menarche; however, therapy was discontinued at age 16-years-old due to loss of care.
On re-presentation in adulthood, laboratory evaluation demonstrated hypergonadotropic hypogonadism with elevated LH (29.9 mIU/mL) and FSH (119 mIU/mL) and suppressed estradiol ( < 5pg/mL) and progesterone (0.1 ng/mL) levels. Hormone replacement therapy was reinitiated with estradiol patch, progesterone and cyclic progesterone (micronized progesterone 100-200mg daily for 14 days per month) to support secondary sexual characteristics and to mitigate long-term risks of osteoporosis and cardiovascular disease.

Discussion/ Conclusion
Turner syndrome comprises a heterogeneous group of genotypic abnormalities with predominantly symptom-directed management aimed at preventing long-term complications. Standard therapy includes growth hormone (GH) induction during childhood until epiphyseal closure. Estradiol and progesterone use are recommended to be administered lifelong. Transdermal estradiol E2 is preferred over oral, with cyclic progesterone initiated after breakthrough bleeding. Patient should have comprehensive screened for osteoporosis, cardiovascular disease, renal anomalies and thyroid dysfunction. Although there is no current definitive cure, emerging research on DNA methylation modulating gene expression can be promising. This case underscores the importance of recognizing rare Xp deletions and ensuring lifelong endocrine surveillance in Turner syndrome.

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