Contribution of Clinical and Biological Mini-Puberty and Genetic Analysis in 57 46,XY Differences of Sex Development:...

Differences of sex development (DSD) is a group of rare congenital conditions defined by chromosomal, gonadal and/or phenotypic discordance or atypical sex. The mini-puberty, corresponding to the transient postnatal activation of the hypothalamic-pituitary-gonadal axis, is an important diagnosis window in the clinical workup of infants with DSD. First objective was to compare clinical data as well as hormone levels during minipuberty between patients with and without a genetic diagnosis. Secondary objective was to assess the positive predictive value of specific hormone levels at M2, which represents the mid-point of mini-puberty, to differentiate between patients with and without a genetic diagnosis by NGS.

Our study included 57 children with 46,XY DSD born between September 2010 and August 2022 who had results from hormone level measurements during mini-puberty and a next-generation sequencing DSD gene panel.

From genetic testing, the diagnostic yield was 49%. Hormone analysis during mini-puberty demonstrated variations in anti-Müllerian hormone, inhibin B, follicle-stimulating hormone and luteinizing hormone levels, with specific patterns observed in certain DSD conditions. Notably, levels of follicle-stimulating hormone >4 IU/L, anti-Müllerian hormone <235 pmol/L, and inhibin B <189 pg/mL at 2 months of life were associated with a higher probability of a genetic diagnosis.

This study proposes a less invasive diagnostic approach for 46,XY DSD children with palpable gonads at birth; it seems a single blood test around the second month of life for comprehensive analysis.