ESPE Abstracts

Background: A common cause of neurodevelopmental impairment in children is congenital hypothyroidism, but can be preventable with adequate screening and proper management. Preterm newborns are more likely to have thyroid dysfunction, with small for gestational age (SGA) being an additional risk factor. However, only few studies addressed the altered thyroid hormone concentrations in the first few weeks of life concluding that Thyroid-Stimulating Hormone (TSH) levels are higher...

Background: The Clock/Bmal1 transcription factor heterodimer regulates the circadian activities of many biological systems, including the hypothalamic-pituitary-adrenal (HPA) axis, by trans-activating or trans-repressing downstream target genes. 1,25 Dihydroxy Vitamin D (Vitamin D), a sterol hormone that is activated by exposure to sunlight, plays a fundamental role in maintaining calcium and phosphorus homeostasis. Recent evidence suggests that the nuclear vi...

Background: The circadian rhythm-generating peripheral Clock/Bmal1 heterodimer complex regulates the circadian activities of many biological systems, including the hypothalamic-pituitary-adrenal (HPA) axis, by trans-activating or trans-repressing downstream target genes.Objective and Hypotheses: To investigate the potential role of elevated cortisol in Clock/Bmal1 heterodimer complex-generated circadian biorhythms, both ...

Background: Vesico-ureteral reflux (VUR) is the most common urologic abnormality seen in children. It represents the backflow of urine from bladder to upper urinary structures due to a defect in closure of uretero-vesical junction. This condition predisposes children to repetitive pyelonephritis associated with renal scarring.Objective: Studies are continuously searching for the potential effect of VUR on growth. We aimed to assess growth indices: height...

Background: A thirty-four months old boy was referred for precocious puberty. He was the first child of healthy non-consanguineous parents. His family history was unremarkable. He had no exposure to oestrogenic endocrine-disrupting chemicals. He had presented secondary sexual characteristics for five months: pubic hair, enlarged testicular volume to 6 ml (Tanner stage P2A1G2) and enlarged penile size. He had a deepening voice and aggressive behavior. He had a significant growt...

Background: Loss of function mutations in KISS1R, which encodes kisspeptin receptor have been reported in very few patients with normosmic isolated hypogonadotropic hypogonadism (nIHH).Objective and hypotheses: To describe the phenotype of the nIHH female patient with a novel homozygous KISS1R mutation and to characterize functionally this mutation. The patient was a 28 year-old Senegalese woman with primary amenorrhea. She was the seco...

Background: Primary generalized glucocorticoid resistance (PGGR) is a rare, familial or sporadic condition, characterized by generalized, partial tissue insensitivity to glucocorticoids. The molecular basis of this condition has been ascribed to mutations in the NR3C1 (human glucocorticoid receptor, hGR) gene, which impair the molecular mechanisms of hGR action and decrease tissue sensitivity to glucocorticoids. However, a considerable number of patients with PGGR do ...

Background: Between the 6000 monogenic disorders, only few are due to a single mutation. Recently, a specific mutation has been described in TUBB3, encoding tubulin beta 3, in the association of Moebius syndrome (MS) and Kallmann syndrome (KS). MS is a congenital paralysis of eye and face’s muscles and can be caused by mutations of TUBB3. KS combines hypogonadotropic hypogonadism and anosmia.Objective and hypotheses: The combination of these two syn...

Background: DMXL2 haploinsufficiency in humans was recently shown to cause the polyendocrine-polyneuropathia syndrome including a GnRH deficiency (OMIM #616113). The neuronal deletion of Dmxl2 in mice (Nes::Cre;Dmxl2loxp/wt) caused infertility and gonadotropic deficiency (Plos Biology 9 e1001952, 2014). Dmxl2 encodes rabconnectin-3α (rbcn-3α), which participates in the control of the V-ATPase activity an...

Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by a dysfunction of the GnRH Axis. The clinical variability of the disease is accompanied by genetic heterogeneity. Indeed, more than 40 genes are implicated in the pathogenesis of this condition. The main goal of this present study was to characterize genetic defects in a large cohort of French CHH patients using a targeted NGS panel.Patients: a cohort of 120 unrelated patients (7...