1 Confusion in gonadal dysgenesis terminology persisting beyond Chicago Consensus Statement on disorders of sexual development Seyyed Mohammad Ghahestani (1) *, Sara Karimi (2) (1) *: Assistant Professor of pediatric urology, Tehran University of Medical Sciences(TUMS), Department of Urology Address: Children Medical Center Hospital, Gharib St, Keshavarz Blvd, Tehran, Iran Email: mgrosva@gmail.com , sm-ghahestani@sina.tums.ac.ir phone:+989128491811 Sara Karimi, Fellow of female urology, Urology Nephrology Research Center(UNRC), Shahid Beheshti Medical University(SBMU) Corresponding and first author: Seyyed Mohammad Ghahestani Address: Labbafinejad Hospital, Urology Nephrology Research Center, Boostan 9th, Pasdaran Ave, Tehran, Iran Phone: +9133004032 Keywords: Sexual development disorder, gonad, dysgenesis, consensus, terminology, sex Abbreviations: DSD: Disorder(difference) in sexual development SO: Streak ovary DT: Dysgenetic testis GD: Gonadal dysgenesis OT-DSD: Ovotesticular disorder(difference) in sexual development mailto:sm-ghahestani@sina.tums.ac.ir 2 A consensus on DSD classification and terminology was published in 2006 under the auspices of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology. Terminology in this group of disorders has social, psychologic and even political and philosophical intricacies, and the medical community should be cautious about any trace of stigmatization or social unfairness. Preceding literature has adopted a confusing approach toward the terminology of gonadal dysgenesis with inconsistent emphasis on either gonadal histology or karyotype. Descriptive words “partial,” ”complete,” and “pure” have been used diversely and sometimes interchangeably. We try to show some inconsistencies below in enumeration: 1) The phrase “partial gonadal dysgenesis” is used as a discriminative term vs mixed gonadal dysgenesis. Since MGD denotes a streak gonad on one side and a dysgenetic testis on the other, the term “partial gonadal dysgenesis” has been used to denote a condition of bearing dysgenetic testes on both sides. 2) A condition of two streak gonads with XX karyotype and without somatic features of Turner syndrome is called 46XX pure gonadal dysgenesis. The word “pure” is presumed to convey a non-mosaic karyotype (46XX). This is somewhat obscure as there are cases of two streak gonads and 45X/46XY karyotype that are mosaic and evade the quoted applicability of the word “pure”. This condition is not covered by the 2006 Chicago statement (1). 3) Complete gonadal dysgenesis has been used to denote cases of bilateral streak ovaries and hypergonadotropic hypogonadism (2). Specifically, Swyer syndrome with 46XY and bilateral streak ovaries has been called 46XY-CGD in the 2006 Consensus Statement (3). Confusingly, cases of pure gonadal dysgenesis have also been called CGD in some essays, sparing the DSD Consensus Statement (2, 4). There are cases of 45X/46XY bilateral SO that have been proposed to be called CGD (4) and 46XY-Pure gonadal dysgenesis in some dissertations (2). Although the DSD Statement attempted to solve the confusion by attributing any terminology to a specific situation, the words partial, complete, and pure are still non- descriptive and difficult to understand regarding the assigned condition. One does not find a clear explanation why the word “partial” is presumed to represent two dysgenetic testes and the word “complete”, two streak ovaries. It is clear that much confusion remained in the 2006 Consensus about the terminology of gonadal dysgenesis conditions as an important subclass of DSD. Confusion in terminology appears to be due to uncertainty in shifting emphasis between karyotype and gonadal histology in each disorder. Any proceedings in terminology must be scientifically well sought and bear significant consequences. Such decisions must be adopted and coined by multidisciplinary conventions. A terminology in any of gonadal dysgenesis conditions should convey these specifications: a) It is one of the gonadal dysgenesis subtypes of DSD. b) Types of dysgenetic gonads: streak ovaries, dysgenetic testes, ovotestis, or undifferentiated c) Karyotype: It must be mentioned if specifically addressed in the definition of the condition, e.g. Swyer syndrome. If the condition is not specifically attributed to a non- 3 mosaic karyotype, it is adequate to declare it as a type of gonadal dysgenesis; this simply denotes that the karyotype may have any combination. We attempted to propose a more descriptive blueprint terminology in Table 1. We aimed to demonstrate this study’s message in a clearer exemplary fashion. There is no doubt that a newer statement on DSD is necessary after fifteen years. . References: 1. Bagci G, Bisgin A, Karauzum SB, Trak B, Luleci G. Complete gonadal dysgenesis 46, XY (Swyer syndrome) in two sisters and their mother's maternal aunt with a female phenotype. Fertility and sterility. 2011;95(5):1786. e1-. e3. 2. Rocha VBC, Guerra-Júnior G, Marques-de-Faria AP, de Mello MP, Maciel-Guerra AT. Complete gonadal dysgenesis in clinical practice: the 46, XY karyotype accounts for more than one third of cases. Fertility and sterility. 2011;96(6):1431-4. 3. Hughes IA, Houk C, Ahmed SF, Lee PA, Society LWPE. Consensus statement on management of intersex disorders. Journal of pediatric urology. 2006;2(3):148-62. 4. Öcal G, Berberoğlu M, Şıklar Z, Ruhi HI, Tükün A, Çamtosun E, et al. The clinical and genetic heterogeneity of mixed gonadal dysgenesis: does “disorders of sexual development (DSD)” classification based on new Chicago consensus cover all sex chromosome DSD? European journal of pediatrics. 2012;171(10):1497-502. 4 Table 1. Confusion in current terminology and proposal of a blueprint Condition Proposed terminology Traditional or frequently cited Consensus 2006(1) 1 GD:SO-DT Asymmetrical gonadal dysgenesis Mixed gonadal dysgenesis MGD 2 46 XX- bilateral DT 46XX- symmetrical testicular GD 46 XX sex reversal De la Chapelle 46-XX testicular DSD 3 46XX-bilateral SO 46 XX symmetrical ovarian GD 46XX-pure gonadal dysgenesis (2) 46 XX complete gonadal dysgenesis (2, 4) 46XX-pure gonadal dysgenesis 4 XO/XY- bilateral SO Mosaic (XO/XY)Symmetrical ovarian gonadal dysgenesis Complete gonadal dysgenesis (2) Not found 5 GD: bilateral DT Symmetrical testicular gonadal dysgenesis Partial gonadal dysgenesis Dysgenetic male Pseudohermaphroditism Partial gonadal dysgenesis 6 46XY bilateral SO 46 XY symmetrical ovarian gonadal dysgenesis 46XY-sex reversal or XX female Swyer syndrome 46 XY complete gonadal dysgenesis 7 OT-DSD True hermaphrodite OT-DSD