Painful ovulation in a 46, XX SRY −ve adult male with SOX9 duplication. (7th June 2017)

• Record Type: Journal Article
• Authors: Shankara Narayana, Nandini; Kean, Anne-Maree; Ewans, Lisa; Ohnesorg, Thomas; Ayers, Katie L; Watson, Geoff; Vasilaras, Arthur; Sinclair, Andrew H; Twigg, Stephen M; Handelsman, David J
• Is Part Of: Endocrinology, diabetes & metabolism case reports. (2017)
• Publication Date: 2017-06-07
• Subjects: Adolescent/young adult -- Female -- Male -- White -- Australia; Ovaries -- Genetics and mutation -- FSH -- LH -- Testosterone -- Sexual development disorders -- Hypogonadism; Gynaecomastia -- Atrophy -- Virilisation (abnormal) -- Infertility -- Hypogonadism -- FSH -- LH -- Sex hormone binding globulin -- Testosterone -- HCG (serum) -- Alpha-fetoprotein -- Histopathology -- Ultrasound scan -- Chromosomal analysis -- Bone age -- Genetic analysis -- Tanner scale -- Testosterone; Unique/unexpected symptoms or presentations of a disease -- June -- 2017; Endocrinology -- Periodicals; Diabetes -- Periodicals; Diabetes Mellitus; Endocrinology; Diabetes; Endocrinology; Case Reports; Periodicals; Periodicals; 616.4
• DOI: 10.1530/EDM-17-0045
• Languages: English
• ISSNs: 2052-0573

Abstract

Summary: 46, XX disorders of sexual development (DSDs) occur rarely and result from disruptions of the genetic pathways underlying gonadal development and differentiation. We present a case of a young phenotypic male with 46, XX SRY-negative ovotesticular DSD resulting from a duplication upstream of SOX9 presenting with a painful testicular mass resulting from ovulation into an ovotestis. We present a literature review of ovulation in phenotypic men and discuss the role of SRY and SOX9 in testicular development, including the role of SOX9 upstream enhancer region duplication in female-to-male sex reversal. Learning points: In mammals, the early gonad is bipotent and can differentiate into either a testis or an ovary. SRY is the master switch in testis determination, responsible for differentiation of the bipotent gonad into testis. SRY activates SOX9 gene, SOX9 as a transcription factor is the second major gene involved in male sex determination. SOX9 drives the proliferation of Sertoli cells and activates AMH/MIS repressing the ovary. SOX9 is sufficient to induce testis formation and can substitute for SRY function. Assessing karyotype and then determination of the presence or absence of Mullerian structures are necessary serial investigations in any case of DSD, except for mixed gonadal dysgenesis identified by karyotype alone. Treatment is ideal in a multidisciplinary setting with considerations to genetic (implications to family and reproductive recurrence risk), psychological aspects (sensitive individualized counseling including patient gender identity and preference), endocrinological (hormone replacement), surgical (cosmetic, prophylactic gonadectomy) fertility preservation and reproductive opportunities and metabolic health (cardiovascular and bones).