Advances in diagnosis and care of persons with DSD over the last decade

It is clear that the major issues raised by the Chicago Disorders of Sex Development (DSD) Consensus meeting primarily the need of more data, especially outcome information, are still not available. Hence, there are insufficient data to merit another consensus statement. However, there has been a major shift in the thinking and approach to the care of patients with DSD. This was a consequence of the emphasis of the need to reconsider the criteria for sex assignment, to incorporate new genetic and hormonal knowledge in the care, and to investigate impact of surgical timing and techniques. Much of the reconsideration is in response to patient, family, social and legal demands, including the need for full disclosure and family or individual participation in decisions. Further, there remains a lack of sufficient information to provide predictors for future gender development. Hence, it still is impossible to develop specific clinical guidelines to apply to patients generally or individually. Thus, it is pertinent to periodically evaluate and assess some of these multifaceted changes. This report discusses cultural and social forces, legal factors, surgical perspectives, treatment shifts including psychological approaches, progress regarding genetic diagnosis, gender issue comparisons with transgender patients, and on-going research studies occurring since the consensus conference. Introduction The consensus report concerning DSD published in 2006 [1,2] was an collective attempt to summarize and evaluate available information about optimizing treatment for DSD and identifying areas where further study was warranted. It has been nearly a decade since the Consensus Conference which: 1) redefined a broad variety of developmental conditions involving the reproductive system as Disorders of Sex Development (DSD), 2) created a new nomenclature based largely upon karyotype, 3) recognized the need to reconsider the criteria for those etiologies in which sex assignment was unclear, 4) reviewed pertinent physical findings and summarized genetic and hormonal criteria for diagnosis, 5) discussed surgical approaches and timing, 6) evaluated gonadal development from the perspective of fertility potential and risk of tumor development, and 7) identified the need for outcome studies including quality of life for * Correspondence: [email protected] Department of Pediatrics, Penn State Hershey Medical Center, The Milton S. Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033, USA Full list of author information is available at the end of the article © 2014 Lee et al.; licensee BioMed Central Ltd Commons Attribution License (http://creativec reproduction in any medium, provided the or Dedication waiver (http://creativecommons.or unless otherwise stated. those with DSD . Major concerns at that conference involved what genital and gonadal surgeries should be done and when these should be performed, and the lack of predictors for future gender development for DSD newborns without a clear diagnosis. This report led to substantial changes in approaches to DSD patients as outlined in the paragraphs of this section below. This includes terminology, imaging techniques and diagnostic criteria, as well as the recognition of uncertainty about determinations of gender development pertinent in those situations when sex assignment is not apparent and is deemed to be necessary. While a shift in the psychological approach is not welldocumented, there is a sense than more transparency and shared decision making and certainly an awareness of the need for review of overall management. While the term DSD has been widely adopted, there have been objections to the use of the word “Disorders” when used to describe less severe DSD cases leading to advocacy for a term to imply a variation of normal, such as “differences” or “variation”. Further, it is unclear how this classification should be applied to conditions that . This is an Open Access article distributed under the terms of the Creative ommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and iginal work is properly credited. The Creative Commons Public Domain g/publicdomain/zero/1.0/) applies to the data made available in this article, Lee et al. International Journal of Pediatric Endocrinology 2014, 2014:19 Page 2 of 13 http://www.ijpeonline.com/content/2014/1/19 do not present at birth with inconsistency between the karyotype, gonads and genital development, such as the less severe forms of congenital adrenal hyperplasia (CAH). While there does not seem to be a consistent opinion in the CARES Foundation there is a push to remove CAH from the DSD nomenclature. The general classification of 46,XX, 46,XY and chromosomal DSD has also been adopted. While this classification is useful at the onset of the assessment toward an etiologic diagnosis, it, like the system it replaced may inappropriately emphasize the role of karyotype in gender development for some affected individuals. The consensus statement included recommendations for sex assignment for a relatively small group of DSD etiologies where outcomes were well-defined and predictable. While for most DSD patients sex assignment is apparent, for the minority for whom it is not, it remains problematic. It was apparent at the Consensus Conference that environment (social rearing as a boy or girl) should not be considered a primary determinant of future gender development for most DSD patients. While it is now broadly recognized that androgen exposure to the central nervous system during mid-fetal life impacts gender development, this effect was not considered to be sufficient to guide sex assignment, particularly in those with 46,XY DSD and some testicular development. As a result, there has been a shift toward male sex assignment for patients in this category [3], with the caveat that assignment in those with dysgenic gonads and partial female and male internal reproductive system development (such as ovotesticular DSD), the process must be highly individualized. Current imaging techniques make it possible to ascertain the physical development beyond the classical Prader or Quigley staging. Additional pertinent information including gonadal and internal reproductive system development, such as level of urethral-vaginal confluence and completeness and symmetry of internal ductal development, are now emphasized as important pre-operative considerations in all DSD surgeries. This approach provides for better assessment of surgical needs as well as the potential for fertility and sexual function. The use of anogential distance [4], felt to be a good physical index of early fetal androgen exposure, and its relationship to outcome in various DSD diagnoses has been explored but as yet seems to have limited practical usefulness in management of DSD patients. Current diagnostic criteria remain largely dependent upon hormonal levels. However, improved availability of anti-Mullerian hormone and inhibin B assays enhance the assessment of gonadal development and broader use of liquid-chromotography-tandem mass-spectrometry has led to improved reliability in the measurement of serum steroid concentrations. This review, which includes only certain aspects regarding the care of those with DSD, has been divided into the following sections: 1) Social issues, 2) Legal issues, 3) Surgical techniques to improve sexual responsiveness and genital appearance, 4) Psychological factors and outcome data, 4) Identification of genetic etiologies of DSD, 5) Gender issues and 7) Brief summaries of active DSD research projects. Similar to the 2006 consensus conference, the aim of this review is to improve the care provided to DSD patients through improvements in diagnostic ability and enhanced collaboration of those different specialties involved in management of DSD