Early Pubertal Progression and Increased 11-Oxygenated Androgens in a Girl with Wiedemann-Steiner Syndrome and a KMT2A Variant: A Case Report

Le résumé fourni par la source

Introduction: The factors that determine the tempo of pubertal progression are not fully understood. Although a few patients with KMT2A variants were noted to have precocious puberty, in addition to various clinical features of Wiedemann-Steiner syndrome (WSS), the hormonal data of these individuals were unreported. Recently, high blood levels of 11-ketotestosterone, a potent 11-oxygenated androgen, were observed in a girl with WSS. Case Presentation: We encountered a Japanese girl who experienced menarche at 9 years and 4 months of age. She showed pubertal levels of LH and estradiol and advanced bone age and was treated with a gonadotropin-releasing hormone analog. She exhibited hirsutism, craniofacial features, and mild intellectual disability but no other clinical features of WSS. Exome sequencing identified a hitherto unreported de novo variant at the splice acceptor site of KMT2A exon 5 (c.3335-1G>A). Her blood levels of 11-oxygenated androgens, androstenedione, and dehydroepiandrosterone were markedly elevated, while those of estrogen and testosterone were within normal ranges. Conclusion: The present case implies possible roles of KMT2A in the hypothalamic-pituitary-gonadal axis or in adrenal steroidogenesis. The results of this study, together with previous findings, imply that overproduction of 11-oxygenated androgens contributes to advanced bone age and hypertrichosis in patients with WSS. Our data merit further validation.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.