ESPE Abstracts

We present the case of a 11-years-old girl who came to our attention for a first critical episode lasting a few minutes, with spontaneous resolution, described as a generalized clonic tonic crisis, which occurred in full well-being. An electroencephalogram (EEG) was performed which showed focal epileptiform anomalies in the right temporal center that spread evoked by hyperpnea and eye closure and an EEG after sleep deprivation that showed an accentuation of the anomalies in ph...

Background: Onset of diabetes in the neonatal period with additional malformations e.g. congenital heart defects should always be suspicious for an underlying genetic disorder. For example, GATA6-mutations were identified in children with congenital heart defects and neonatal diabetes. The latter may be due to pancreas agenesis. Herein we present a novel GATA6-mutation in a boy with transient neonatal diabetes, diaphragmatic hernia, congenital heart defect and early onset scol...

Introduction: Mammalian sex development is directly dependent on gonadal determination. Whole exome sequencing in patients with differences of sex development (DSD) allows the discovery of new factors involved in human sex development. One of these factors is NWD1 (NACHT and WD repeat domain containing 1) a cytosolic protein that seems to play a role in modulating androgen receptor signaling. We identified variants in the NWD1 gene in six und...

Abstract: Steroidogenic factor 1 (SF1)/"nuclear receptor subfamily 5 group A member 1" (NR5A1) is involved in adrenal and gonadal development, steroidogenesis and reproduction. The first patient, published in 1999 presented with a 46,XY difference of sex development (DSD) and adrenal insufficiency. The following year the first female patient with only adrenal insufficiency was described. Since then, heterozygous changes in SF-1/NR5A1 causing 46,XY DSD ...

Background: Variants in the estrogen receptor α (ESR1) have previously been described in male and female patients presenting with estrogen resistance. Estrogen resistance is characterized by delayed bone-age, early-onset osteoporosis, delayed puberty and multicystic ovaries in women. So far, no clinical consequences of variants in the estrogen receptor β (ESR2) have been reported in 46,XX patients, although ESR2 variants have previously been implicated in 46,XY DSD p...

Background: Klinefelter syndrome (KS) has long-term consequences on bone health. However, studies regarding bone status and metabolism in childhood and adolescence are very rare.Objective and hypotheses: The purpose of our study was to evaluate bone status and metabolism in a cohort of KS children and adolescents.Method: This cross-sectional study involves 40 (mean age 13.7±3.8 years) KS children and adolescents and 80 age-mat...

Background: However, no study has considered the effect of a supernumerary X chromosome on bone mineral status and bone metabolism.Objective and hypotheses: To evaluate bone mineral status and metabolism in a cohort of patients with nonmosaic triple X syndrome.Method: Nineteen girls (median age 10.9, range 7.7–15.9 years) with nonmosaic triple X syndrome were cross-sectionally studied and compared to an age- and body-size-matc...

Background: Primary hypoaldosteronism (PA) is a rare inborn disorder with life-threatening symptoms in newborns and infants due to an aldosterone synthase defect. As plasma aldosterone concentration (PAC) can remain in the normal range, interpretation of the laboratory findings could be difficult and might lead to delayed initiation of therapy.Objective and Hypotheses: This study aims to show that PAC/PRC (plasma renin concentration) rat...

Background/Introduction: Whole exome sequencing (WES) revolutionized clinical genetics in patients with differences of sex development (DSD). However, our ability to interpret WES data is limited by our incomplete understanding of the mechanisms involved in DSD. Thus, we created a methodology that scores potential candidates based on single cells transcriptomics of human male gonadal cells and applied it to WES data from a cohort of genetically male (46,XY) DS...

Background: Congenital Hypopituitarism (CH) is a rare heterogeneous genetic disorder characterized by the deficiency of pituitary hormones. CH can be associated with extra pituitary phenotypes such as midline craniofacial malformations. To date, a minority of patients carry pathogenic variants in more than 30 genes, and thus more than 80% of cases remain unresolved.Objective: To identify de novo pathogenic variants in no...