ESPE Abstracts

Background: The phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway is central for cell cycle control, differentiation, migration, and metabolism. Unrestricted growth of adipose tissue in particular is frequently seen in humans with germline PTEN and mosaic activating PIK3CA mutations, respectively.Objective and hypotheses: We assume that adipocytes from affected tissue show hyperproliferation and modified dif...

The pervasiveness of noncoding transcription has revolutionized our understanding of gene regulation. Although not yet fully catalogued in terms of numbers, mammalian genomes express a broad spectrum of, small and long, noncoding RNAs. Whereas small noncoding RNAs like microRNAs and their role in energy metabolism and glucose handling are rather well understood, we have little understanding concerning the metaboregulatory properties of those 10,000s of long noncoding RNAs (lnc...

Congenital hypothyroidism (CH) is a partial or complete loss of function of the thyroid gland resulting in absent or decreased synthesis and secretion of thyroid hormones affecting infants since birth. Mutations of the hTPO gene are associated with autosomal recessive forms of CH. Based on our TSH screening results, the number of children with eutopic primary CH is increasing. Molecular biology techniques can identify the CH genetic cause after selection based on family histor...

Background: Congenital adrenal hyperplasia (CAH) due to a CYP21A2 defect (autosomal recessive) leads to salt wasting (SW), simple virilizing (SV), or non-classical (NC) phenotypes basically depending on residual 21-hydroxylase (21-OH) function on the least affected allele.Objective and Hypotheses: To test prediction of CAH phenotype based on genotype classification.Method: Patient data from 37 centers were retrieved from a...

Context: Prenatal dexamethasone (Dex) therapy is used in female foetuses with congenital adrenal hyperplasia (CAH) to suppress adrenal androgen excess and prevent virilisation of the external genitalia. The prenatal dexamethasone dose of 20 µg/kg/d has been used for decades in prenatal CAH. Despite the risks for the treated mother and potentially for the unborn child, no clinical study or evaluation had been conducted in order to determine a Dex dose with a scientific rat...

The Silver-Russel syndrome (SRS) is characterized by an intrauterine growth retardation accompanied by postnatal growth deficiency. Affected individuals typically have proportionately short statue, finger deformities as well as typical facial features. About 10% of individuals with SRS have maternal uniparental disomy for chromosome 7 (UPD7) and 35%–50% showed hypomethylation of the parental imprinting center region 1 (ICR1) of chromosome 11p15.5. In the recent past also ...

Differences of sex development (DSD) occur in about 1 in 3000 newborns in Switzerland. The indication and timing of genitoplasty in children with DSDs is a complex issue. In 2012 the Swiss National Advisory Commission on Biomedical Ethics published its position against early irreversible interventions in order to "normalize" the aspect of the external genitalia.We report the case of a child with a 46,XX DSD due to a classical form of congenital a...

Background/aim: The PTEN hamartoma tumor syndrome (PHTS) is an overgrowth syndrome caused mainly by germline mutations in the tumor suppressor PTEN. Patients are predisposed for the development of malignant and benign tumors. Children and adolescents with PHTS frequently develop single or multiple lipomas. PTEN antagonizes the phosphatidylinositide3-kinase/AKT/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway, which promotes proliferation and differentiation in ...

Background: The leptin signaling cascade is a crucial regulator of satiety and energy homeostasis in the hypothalamus, comprising extracellular leptin binding to its receptor, phosphorylation and nuclear translocation of STAT3 (signal transducer and activator of transcription 3) and consecutively the generation of a central satiety signal via neuropeptide secretion. We identified three variants in the extracellular domains of the LEPR gene in two children with severe ...

Background: Treatment of CAH in children is compromised by the pharmacokinetic of available hydrocortisone (HC) preparations resulting in un-physiological early morning rise of ACTH followed by elevated androgens. HC substitution usually follows a fixed dosing scheme (50%–25%–25%) monitored by blood sampling.Objective and hypotheses: We describe the individualized optimization of HC treatment by 17-OHP saliva profiles and the effects of the res...