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.

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: This retrospective descriptive case series included 43 pediatric patients with TXS diagnosed at Jiangxi Provincial Children's Hospital between January 2019 and November 2024. Patients were classified into three groups: non-mosaic, X-monosomy mosaic (containing 45,X cell lines), and non-X-monosomy mosaic groups. Clinical data, including anthropometric measurements, sex hormones, pelvic ultrasound, bone age, and comorbidities, were collected. G-banding karyotyping was performed in all patients, and fluorescence in situ hybridization (FISH) was additionally performed in selected cases. Given the small subgroup sizes, analyses were descriptive without formal between-group hypothesis testing. Results: Among the 43 patients, 31 (72.1%) were non-mosaic, 9 (20.9%) were X-monosomy mosaic, and 3 (7.0%) were non-X-monosomy mosaic. Fifteen patients (34.9%) experienced spontaneous menarche at a mean age of 11.13±1.28 years. The X-monosomy mosaic subgroup showed Turner syndrome-like features, including delayed bone age (mean difference +1.36 years), skeletal anomalies (3/9, 33.3%), and renal anomalies (2/9, 22.2%). Neuropsychiatric disorders were the most common comorbidity overall (11/43, 25.6%), particularly in the non-mosaic group. FISH refinement identified additional low-frequency cell lines in selected patients, highlighting cytogenetic complexity beyond routine karyotyping. 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.