@article{TP153979,
author = {Ya-Qin Feng and Wen-Ting Li and Hai-Ying Zou and Qing-Bo Xu and Li Yang},
title = {Clinical phenotype, gonadal development, and comorbidity spectrum in 43 children with triple X syndrome: a single-center retrospective descriptive case series with cytogenetic refinement in patients with and without X-monosomy-containing cell lines},
journal = {Translational Pediatrics},
volume = {15},
number = {6},
year = {2026},
keywords = {},
abstract = {Background: Triple X syndrome (TXS) is a common yet under-diagnosed sex chromosome aneuploidy with significant phenotypic heterogeneity. Previous studies have typically described TXS as a homogeneous entity, lacking karyotype-stratified analysis. This study aimed to compare clinical phenotypes, gonadal development, and comorbidity profiles across karyotype subgroups in pediatric TXS patients.Methods: In this single-center retrospective chart review with descriptive subgroup characterization (no formal between-group hypothesis tests performed given the small subgroup sizes), we analyzed clinical data from 43 TXS patients (aged 3 days to 16 years) diagnosed at Jiangxi Provincial Children’s Hospital between January 2019 and November 2024. Patients were stratified into three subgroups: non-mosaic group, X-monosomy mosaic group (containing 45,X cell lines), and non-X-monosomy mosaic group (47,XXX/46,XX without 45,X cell lines). Karyotyping was performed by G-banding analysis of peripheral blood lymphocytes (≥20 metaphases routinely; ≥30 if mosaicism was suspected); fluorescence in situ hybridization (FISH) counting ≥200 interphase nuclei was used in 5 selected cases (where mosaicism was suspected, the phenotype was atypical, or a critical clinical decision required cytogenetic refinement) to confirm or refine mosaicism, and a 5% threshold was applied for retaining low-frequency cell lines. Data included karyotype, anthropometric measurements [including height standard deviation score (HtSDS) and body mass index (BMI) standard deviation score (BMISDS)], sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH)], uterine/ovarian ultrasound, and bone age.Results: Of 43 patients, 31 (72.1%) were non-mosaic, 9 (20.9%) were X-monosomy mosaic, and 3 (7.0%) were non-X-monosomy mosaic. The median age at diagnosis was 7.58 years and median height was 117.6 cm. Fifteen patients (34.9%) experienced spontaneous menarche at a mean age of 11.13±1.28 years, which appeared earlier than the commonly cited general population average (~12.0 years), although a formal statistical comparison was not performed. For descriptive purposes, mean bone age difference (chronological age − bone age) was +1.36 years in the X-monosomy mosaic subgroup (n=7 with bone age data) and −0.10 years in the non-mosaic subgroup (n=20 with bone age data); these subgroup-level descriptions are presented in parallel without formal between-group testing. Comorbidity profiles by subgroup are reported descriptively: across the cohort, neuropsychiatric disorders were the most prevalent comorbidity (11/43, 25.6%); within the X-monosomy mosaic subgroup, skeletal anomalies (3/9, 33.3%) and renal anomalies (2/9, 22.2%) were observed, a pattern consistent with features known in Turner syndrome. One patient was diagnosed with premature ovarian insufficiency (POI) (peak FSH 57.16 U/L, AMH 0.12 ng/mL).Conclusions: In this descriptive single-center case series, patients with X-monosomy-containing cell lines were observed to have phenotypic features overlapping both Turner syndrome (disproportionate bone age delay, renal/skeletal anomalies) and typical 47,XXX (neuropsychiatric findings). Given the small subgroup sizes and the single-center design, these subgroup-level descriptions are presented to inform future hypothesis-driven studies rather than to support formal between-group conclusions. We outline a tentative, practice-informed framework intended to support—rather than replace—individualized multidisciplinary follow-up; prospective multi-center validation is required before adoption as a clinical management algorithm.},
issn = {2224-4344}, url = {https://tp.amegroups.org/article/view/153979}
}