ESPE Abstracts

Background: Actual surgical procedures for the treatment of patients with VSD (Variation of Sex Development), in particular severe hypospadias, are associated with frequent post-operative complications.Objective and hypotheses: Tissue engineered collagen tubes are a promising alternative.Method: We elaborated a new, two layered, collagen based tube that can be sutured. Mechanical testing proved a better resistance of those tubes co...

Background: Turner syndrome (TS) arises from a complete or partial loss of one X chromosome (45,X) and is the most common genetic cause of primary ovarian insufficiency (POI) in women. Surprisingly little is understood about the pathogenesis of POI in TS beyond an acknowledged germ cell loss throughout the second trimester. Although X chromosome haploinsufficiency likely contributes, the variability in reproductive phenotype in 45,X TS suggests it is not the o...

Background: Melanocortin 4 receptor (MC4R) deficiency is the commonest monogenic form of non-syndromic obesity. MC4R is a seven transmembrane G-protein coupled receptor implicated in central regulation of body weight. The loss-of-function mutations in MC4R gene will contribute to early-onset obesity associated with hyperinsulinemia, hyperphagia and “binge eating”. We aim to determine the prevalence of MC4R variants in a Pediatrics...

Background: Childhood onset growth hormone deficiency (CO-GHD) may contribute to low bone mass and alterations of body composition. However, the mechanisms by which CO-GHD effects bone health are not yet clearly defined.Objective and hypotheses: To evaluate musculoskeletal health in CO-GHD subjects at initial evaluation and retesting after final height.Method: A cross-sectional study of assessing bone health and body composition by...

Background: Classical salt wasting congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a rare disorder, as is isolated growth hormone (GH) deficiency Type II (IGHD II) due to mutation of the growth hormone gene GH1. Here we describe the unusual case of a girl with concurrent 21OHD and IGHD II and its complex diagnostic work up. A 15.3-year-old girl presented with classical salt wasting CAH due to 21OHD and short stature (height 148...

Introduction: Ovary development was once considered a largely passive process. RNA sequencing (RNAseq) approaches have allowed us to begin to characterise ovary development in previously unparalleled detail, revealing the process to be complex and, still, little understood. A challenge is synthesising and using these data to advance our understanding of clinical disease. Through a clinically-focused lens, we elucidate novel aspects of the transcriptional lands...

Background: States of vitamin D insufficiency are important determinants of rickets, as well as osteoporosis and other common complex disorders like diabetes, cancer, and infectious diseases. Although, serum concentrations of the vitamin D metabolites are primarily driven by vitamin D supply (by diet or cutaneous synthesis), there is emerging evidence to suggest that single nucleotide variants (SNVs) are important genetic determinants.Objective and hypot...

Background: The Low dose dexamethasone suppression test (LDDST) is an important investigation for suspected Cushing’s Syndrome (CS). The traditional definition of normal suppression of serum cortisol to ≤50 nmol/l during the LDDST (0.5 mg 6 hrly × 48 h) comes from a time when biochemical autoanalysers did not routinely detect very low values. Previous studies reported 5.1–8.3% of patients with Cushing’s Disease (CD) suppressed to <50 nmol/l at 48 ...

Human growth is a complex trait. A considerable number of gene defects have been shown to cause short stature, but there are only few examples of genetic causes of non-syndromic tall stature. Besides rare variants with large effects and common risk alleles with small effect size, oligogenic effects may contribute to this phenotype. Exome sequencing was carried out in a tall male (height 3.5 SDS) and his parents. Filtered damaging variants with high CADD scores were validated b...

Background: Patients with congenital adrenal hyperplasia (CAH) are glucocorticoid deficient and require cortisol replacement to maintain homeostasis and prevent adrenal crises. Hydrocortisone dosing needs to be individualized because of variable cortisol clearance rates. Patients are thus prone to be either over or undertreated, both of which compromises final height.Objective and hypotheses: Performing 24-h cortisol profiling serially may allow for more...