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.