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 near-final height.
Near-final height was similar between the two genitalia-based groups in children with 45,X/46,XY mosaicism.
Growth in children with 45,X/46,XY mosaicism aligned more closely with female reference curves than male reference curves.
Bone age assessment yielded discordant results depending on whether male or female standards were applied.
Female-based predicted adult height (PAH) approximated near-final height more accurately than male-based PAH or target height (TH).
Near-final height was similar in individuals who did and did not receive growth hormone (GH) treatment, though interpretation was limited.
The study was a multicenter retrospective registry-based cohort study including 95 cases of 45,X/46,XY mosaicism from 26 centers.
This research examined how children with a specific chromosomal condition called 45,X/46,XY mosaicism — where some cells have one X chromosome and no Y, and others have both X and Y chromosomes — grow over time and how their bones mature. The study looked at data from 95 children across 26 medical centers worldwide, tracking height and bone development. A key question was which growth charts (male or female) best described these children's growth and could most accurately predict their adult height. The researchers found that these children's growth patterns followed female reference charts much more closely than male ones. When their near-final heights were compared to female growth standards, they fell only slightly below average (-0.3 to -0.7 standard deviations), whereas compared to male standards, they fell well below average (-1.6 to -2.0 standard deviations). Similarly, bone maturation was better described using female standards. Using female-based calculations to predict adult height gave more accurate estimates than male-based calculations or estimates based on parental heights. Near-final heights were similar regardless of whether children had more male-typical or more female-typical genitalia at birth. This research suggests that clinicians should use female growth charts and female bone age standards when monitoring growth and predicting adult height in children with 45,X/46,XY mosaicism, regardless of how their genitalia appear. The study also noted that growth hormone treatment outcomes could not be clearly assessed due to small numbers and differences between treated and untreated groups, highlighting the need for larger, prospective studies to better guide treatment decisions for this population.
Bosmans J, Herregods N, van Gremberghe I, van den Akker E, Atapattu N, Baronio F, et al.. (2026). Growth patterns and bone maturation in children with sex chromosomal (45,X/46,XY) differences of sex development.. European journal of endocrinology. https://doi.org/10.1093/ejendo/lvag092