Phenotypic Spectrum and Gonadal Outcomes in Children with 45,X/46,XY Mosaicism: A Longitudinal Cohort Study
https://doi.org/10.15605/jafes.041.S1
- Author:
Vaidevi Poospalinggam
1
;
Janet Hong
1
;
Arini Nuran
1
;
Nalini M Selveindran
1
Author Information
1. Paediatric Endocrine Unit, Hospital Putrajaya
- Publication Type:Journal Article
- MeSH:
Child;
Longitudinal Studies;
Mosaicism
- From:
Journal of the ASEAN Federation of Endocrine Societies
2026;41(S1):135-136
- CountryPhilippines
- Language:English
-
Abstract:
Introduction:45,X/46,XY mosaicism is a rare disorder of sex development
characterized by marked phenotypic variability, ranging
from typical male or female genitalia to significant genital
ambiguity. Data describing long-term clinical outcomes
in affected patients remain limited. This study aimed to
characterize the phenotypic spectrum and longitudinal outcomes of patients with 45,X/46,XY mosaicism, focusing on
growth, associated comorbidities, and gonadal pathology.
Methodology:We conducted a retrospective longitudinal study at a tertiary
paediatric endocrine referral centre between January 2006
and January 2025. Patients with cytogenetically confirmed
45,X/46,XY mosaicism or related variants were included.
Clinical presentation, karyotype, anthropometry, hormonal
profiles, imaging findings, and gonadal histology were
reviewed. External genital phenotype was quantified using
the External Masculinization Score (EMS). Height was
expressed as standard deviation scores (SDS) relative to
population norms and compared with genetic potential.
Results:Fourteen patients (10 males, 4 females) with 45,X/46,XY
mosaicism were identified. Ambiguous genitalia was the
predominant presenting feature, observed in 11 of 12
patients with available phenotype data. Growth impairment
was common; median height SDS was −2.62 (range −3.26
to −2.00) in females and −0.46 (range 0.13 to −1.70) in
males, both below expected genetic potential. Associated
congenital anomalies were present in 25% of patients,
including cardiac and renal abnormalities. Male patients
demonstrated variable degrees of undervirilization with a
median EMS of 4.5 (3.75–7.25). Müllerian duct remnants
were identified in 66% of patients on imaging. Testicular
microlithiasis was observed in two males. During follow-up,
two patients underwent gender reassignment. Histological
analysis of 14 gonads obtained via gonadectomy or biopsy revealed abnormal gonadal architecture in all cases. All
intra-abdominal gonads demonstrated streak gonads or
dysgenetic testicular tissue.
Conclusion:45,X/46,XY mosaicism demonstrates a broad phenotypic
spectrum with frequent genital ambiguity, growth
impairment, and abnormal gonadal development. The high
prevalence of gonadal dysgenesis underscores the importance of careful surveillance and individualized multidisciplinary management guided by clinical, endocrine,
and histopathological findings.
- Full text:202608051422387075EP_P002.pdf
