ESPE Abstracts

Background: While many causes of 46,XY disorders of sex development (DSD) have been elucidated, the mechanisms leading to 46,XX testicular or ovotesticular DSD are poorly understood. It has been hypothesized that both conditions may represent a phenotypic spectrum and that they might be caused by (different) mutations in the same genes.Methods: Whole exome sequencing was used to identify the molecular cause in ten unrelated patients with 46,XX (ovo)testi...

Background: Extensive and time-consuming hormonal and genetic work-up provides a genetic diagnosis in around 20% of 46,XY cases with ambiguous genitalia. It is currently unclear if such extensive screening might also be indicated in 46,XY newborns with milder undervirilization.Method: All 46,XY neonates and infants (n=32, EMS 2–12) referred to our pediatric endocrine service for atypical male genitalia in the period 2007–2013 were inve...

Background: Hypospadias affects approximately 1/200 newborn males. Based on the testicular dysgenesis syndrome hypothesis, some may be suspected of having persistent testicular dysfunction later in life. Few clinical data currently support this hypothesis.Methods: Cross-sectional assessment of hypospadias cases (n = 193) and controls (n = 50), aged 16-21 years, recruited at Ghent University Hospital and...

Background: Bilateral testicular regression (BTR) is characterized by the absence of both testicles in a newborn male or shortly thereafter, and presenting as bilateral cryptorchidism with undetectable AMH levels and the absence of Müllerian structures on pelvic ultrasound. Depending on when the regression occurs during fetal development, the condition can be associated with a micropenis. Few studies have explored the etiology and long-term outcome of BTR...

Objective: Adrenal cortisol production occurs through a biosynthetic pathway which depends on NADH and NADPH for energy supply. The mitochondrial respiratory chain and the reactive oxygen species (ROS) detoxification system are therefore important for steroidogenesis. Mitochondrial dysfunction leading to oxidative stress has been implicated in the pathogenesis of several adrenal conditions. Nonetheless, only very few patients with variants in one gene of the R...

Background: Hetero- and homozygous mutations in Steroidogenic Factor1 (SF1, NR5A1) cause 46,XY and 46,XX disorders of sex development (DSD), azoospermia, and primary ovarian insufficiency. NR5A1 is also involved in embryonic spleen development, by transactivation of T-cell Leukemia Homeobox 1 (TLX1). Hypo- or asplenism have occasionally been observed in DSD patients with NR5A1 mutations.<p clas...

Background/Aims: Cryptorchidism or undescended testis is a prevalent congenital urogenital condition affecting male newborns with an incidence rate ranging from 1.0 to 4.6%. Mouse models have implicated INSL3 and its receptor RXFP2 (formerly known as GREAT or LGR8) in the development of the condition. RXFP2 acts as a G protein-coupled receptor that triggers the generation of cAMP by binding INSL3. But despite the established role in testicular descent, so far ...

Background: Long-term outcome studies on bilateral testicular regression (BTR) are currently lacking, hampering counseling of patients and parents. Although a vascular origin was initially reported, recent studies revealed a genetic origin in a subset of patients (i.e. DHX37 gene variants). How this relates to patient outcomes remains unclear.Methods: Thirty-five patients with BTR were recruited in eight Belgian centers ...