[Contribution of clinical, biological mini-puberty and genetic analysis in 57 46,XY DSD: a monocentric retrospective cohort].

Abstract

Introduction: 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 to compare clinical data as well as hormone levels during minipuberty between patients with and without a genetic diagnose. Secondary objectives were to assess the positive predictive value of specific hormone levels at M2 , the mid-point of mini-puberty, of age to differentiate between patients with and without a genetic diagnose by NGS.

Methods: 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.

Results: 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 diagnose.

Conclusion: 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.