ESPE Abstracts

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: 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 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: 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...

Background: Congenital thyroid dysgenesis usually occurs sporadically and may even be discordant in monozygotic twins. However, when caused by inactivating mutations in the TSH receptor (TSHR) it can be inherited recessively, typically resulting in thyroid gland hypoplasia. We present a new familial case of thyroid dysgenesis with two siblings of consanguineous parents. The daughter was identified in neonatal screening with severely elevated TSH and thyroid agenesis on ultraso...

Background: Tuberous sclerosis (TS) is an autosomal dominant neurocutaneous disorder involving many organ systems. The frequency of TS is around one per 5000 to 10 000 live births and is caused by mutation in the TSC1 or TSC2 genes. Autoimmune polyglandular syndrome type 2 (APS2) is an endocrinopathy characterized by two or more autoimmune diseases. Several susceptibility genes are known. The prevalence of APS2 is around 1:20 000.Object...

Background: Patients with PTEN (phosphatase and tensin homolog) hamartoma tumor syndrome and germ line mutations in PTEN frequently develop lipomatosis, for which there is no standard treatment. Rapamycin was shown to reduce the growth of lipoma cells with heterozygous PTEN deficiency in vitro, but concomitantly induced an up regulation of AKT phosphorylation.Objective and hypotheses: Since it was shown that resveratrol stabilizes PTEN,...

Background: Primary IGF1 deficiency (PIGFD) is a rare condition defined by low IGF1 levels, GH sufficiency and absence of secondary causes of growth failure. PIGFD is an approved indication for treatment with recombinant IGF1 (rIGF1). Its genetic causes remain largely unknown.Objective and hypotheses: To elucidate genetic causes of PIGFD.Method: Clinical phenotyping followed by trio-based whole-exome sequencing (WES) in 11 complete...