Growth patterns and bone maturation in children with sex chromosomal (45,X/46,XY) differences of sex development

Importance:

Growth patterns and optimal methods for predicting finale height in individuals with 45,X/46,XY mosaicism remain insufficiently characterized. 

Objective: 

To assess growth patterns and bone maturations in children with 45,X/46,XY mosaicism and to optimize final height prediction. 

Design: 

Multicenter retrospective registry-based cohort study. 

Setting: 

Twenty-six participating centers contributing data.

Participants: 

Ninety-five cases of 45,X/46,XY mosaicism were include. Longitudinal growth data were available for 54 participants and stratified by external genitalia score (EGS): group 1 (EGS 0-4) and group 2 (EGS 4.5-12). 

Intervention(s) or exposure(s): 

Growth and bone maturation were evaluated based on male and female references. Growth hormone (GH) treatment outcomes were analyzed. 

Main outcome(s) and measure(s): 

Mean height SD score (SDS), bone age assessed centrally using the Greulich and Pyle, predicted adult height (PAH), target height (TH) and near-final height (nFH).

Results: 

Mean nFH was 157.5 cm in Group 1 and 160.3 cm in Group 2 (n.s.). Growth aligned more closely with female reference curves, with nFH at -0.7 SDS (Group 1) and -0.3 SDS (Group 2) on female charts, and -2.0 and -1.6 SDS on male charts. Bone age was delayed using female standards and advanced using male standards. Female-based PAH slightly underestimated nFH, whereas male-based PAH slightly overestimated it. PAH approximated nFH more accurately than TH. nFH was similar in those who did and did not receive GH treatment, although interpretation was limited by small sample size and treatment bias.

Conclusion and relevance: 

Female growth charts and bone age readings best reflect longitudinal growth and maturation in individuals with 45,X/46,XY DSD and provide the most accurate prediction of nFH. Larger prospective studies are needed to guide evidence-based treatment decisions.