Martina Rodie

Changes Over Time in Sex Assignment for Disorders of Sex Development

BACKGROUND AND OBJECTIVE: It is unclear whether the proportion of infants with a disorder of sex development who are raised as male or female has changed over time. The temporal trends in sex assignment of affected cases entered in the International Disorder of Sex Development (I-DSD) Registry were studied. METHODS: Cases of disorders of sex development reported as partial androgen insensitivity syndrome (PAIS; n = 118), disorder of gonadal development (DGD; n = 232), and disorder of androgen synthesis (DAS; n = 104) were divided into those who were born before 1990, 1990–1999, and after 1999. External appearance of the genitalia was described by the external masculinization score. RESULTS: The median (5th–95th percentile) external masculinization scores of those infants with PAIS, DGD, and DAS who were raised as boys were 6 (2–9), 6 (3–9), and 6 (1–12), respectively, and were significantly higher than in those raised as girls (2 [0–6], 2 [0–7], and 0 [0–5], respectively); this difference was maintained in the 3 temporal birth cohorts (P < .01). Of the 118 cases in the pre-1990 cohort, 41 (35%) were raised as boys; of the 148 cases in the 1990–1999 cohort, 60 (41%) were raised as boys; and of the 188 cases in the post-1999 cohort, 128 (68%) were raised as boys. CONCLUSIONS: Although there is an association between the external appearance of the genitalia and the choice of sex assignment, there are clear temporal trends in this practice pointing toward an increased likelihood of affected infants being raised as boys. The impact of this change in practice on long-term health outcomes requires additional focus.

Novel associations in disorders of sex development: Findings from the I-DSD registry

Context: The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases. Objective: To report the range of associated conditions identified in the international DSD (I-DSD) Registry. Design, Setting, and Patients: Anonymized data were extracted from the I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations, and associated anomalies. If necessary, clarification was sought from the reporting clinician. Results: Of 649 accessible cases, associated conditions occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two conditions, 20 (12%) had three conditions, and 14 (8%) had four or more conditions. Karyotypes with most frequently reported associations included 45,X with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112 cases of 46,XY DSD, the commonest conditions included small for gestational age in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these had confirmed androgen receptor mutations. Conclusions: Over a quarter of the cases in the I-DSD Registry have an additional condition. These associations can direct investigators toward novel genetic etiology and also highlight the need for more holistic care of the affected person.

The European Disorder of Sex Development Registry: A Virtual Research Environment

Disorders of sex development (DSD) are a rare group of conditions which require further research. Effective research into understanding the aetiology, as well as long-term outcome of these rare conditions, requires multicentre collaboration often across national boundaries. The EU-funded EuroDSD programme (www.eurodsd.eu) is one such collaboration involving clinical centres and clinical and genetic experts across Europe. At the heart of the EuroDSD collaboration is a European DSD registry and a targeted virtual research environment (VRE) that supports the sharing of DSD data. Security, ethics and information governance are cornerstones of this infrastructure. This paper describes the infrastructure that has been developed, the inherent challenges in security, availability and dependability that must be overcome for the enterprise to succeed and provides a sample of the data that are stored in the registry along with a summary analysis of the current data sets.

Factors that influence the decision to perform a Karyotype in suspected disorders of sex development: lessons from the Scottish genital anomaly network register

Background: Although a karyotype represents the first objective evidence of investigating a case of suspected disorder of sex development (DSD), the factors that influence the clinician’s decision to initiate investigations are unclear. Methods: Cases of suspected DSD in Scotland were identified through the Scottish Genital Anomaly Network (SGAN) Register. The timing as well as other factors that influence the decision to perform a karyotype were subsequently studied. Results: Out of the 572 cases on the register, 383 (67%) were classified as having a non-specific disorder of under-masculinisation. In 463 (81%) cases, the sex of rearing was male, in 71 (12%) female, and in 38 (7%) cases data regarding sex of rearing were unavailable. A karyotype was reported to have been performed in 153/572 (27%) cases. Infants in Scotland with suspected DSD are more likely to have a karyotype performed in the presence of a low external masculinisation score, bilateral impalpable testes, proximal hypospadias, or associated malformations. Discussion: These data represent the first attempt at benchmarking the decision to check a karyotype and investigate infants with suspected DSD. Whilst this decision may be related to the complexity of the genital anomaly, there are other factors that may influence this decision, and these require further exploration through more rigorous systems for data collection.