Factors That Influence the Decision to Perform a Karyotype in Suspected Disorders of Sex Development: Lessons from the Scottish Genital Anomaly Network Register

Abstract

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.

Perfil de pacientes com anormalidades geniturinárias atendidos em serviço de genética clínica no sistema único de saúde

“…Consistent with the literature, the analysis of these characteristics revealed that, although there was a predominance of subjects with ambiguous genitalia, derived from Wolff and 46,XY karyotype, none of these parameters alone may be considered for determination of diagnosis and treatment 46 – 8 , 10 , 11 , 19 – 21 …”

Histological Assessment of Gonads in DSD: Relevance for Clinical Management

“…The resulting phenotypic variation may range from a typical aspect of internal and external genital characteristics to subtle physical alterations to a significant health disorder with major consequences on long-term outcome. The prevalence of atypical genitalia is about 5 per 1,000 births, and approximately 75% of these cases present as hypospadias in boys [Ahmed et al, 2004;Rodie et al, 2011;Nordenvall et al, …”

“…Of infants with atypical genitalia, about 80% are assigned the male and 15% the female gender [Rodie et al, 2011]. Individuals with a suspected DSD are actually grouped according to their (peripheral blood-based) karyotype as 46,XX DSD, 46,XY DSD, and sex chromosome DSD.…”

“…DSD can be associated with health problems, mainly related to functioning of the cardiovascular system, central nervous system, the skeleton, renal system, or neurocognitive development [Mohnach et al, 2008;Rodie et al, 2011;Cox et al, 2013]. Of significant concern for patients with DSD is the risk of developing a malignant germ cell tumor, referred to as germ cell cancer (GCC) [Cools et al, 2006a].…”

Association Between Extra-Genital Congenital Anomalies and Hypospadias Outcome

“…More recently, it has also been reported that the outcome may also be influenced by the underlying genetic condition with a higher likelihood of multiple hypospadias surgery in those with genetically proven partial androgen insensitivity syndrome [LucasHerald et al, 2016]. However, the extent of investigations that are performed in boys to understand the underlying cause in hypospadias is very variable [Rodie et al, 2011;Swartz et al, 2017], with some studies identifying the presence of extra-genital anomalies as a factor that influences the likelihood of undertaking investigations [Rodie et al, 2011]. An association between extra-genital congenital anomalies and complications following hypospadias surgery has been rarely studied [Lu et al, 2017].…”