ESPE Abstracts

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: 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...

Objectives: To describe clinical, hormonal and genetic findings of an under-virilized infant male, 13 month old, of afghani origin, presented at the emergency department with salt-wasting adrenal crisis.Case report: The patient, a 13 month old male infant, presented at the emergency department with complaints of vomiting and fever. Physical examination was significant for severe dehydration along with perineal hypospadia...

Kallman syndrome is defined by the association of anosmia due to an agenesis of the olfactory bulbs and hypogonadotropic hypogonadism due to a GnRH deficiency which is currently explained by a deficit of GnRH neuron migration from the olfactory placode toward the hypothalamus. In fact, the X-linked form of KS is due to loss of function mutations in ANOS1 which encodes an extracellular protein (ANOSMIN) interacting with cell membrane heparin sulfate proteoglycans but a...

Background: Acquisition and maintenance of fertility in mammals rely on the function of Gonadotropin Releasing Hormone (GnRH) neurons. During the juvenile period, GnRH neurons undergo morphological maturation, which involves changes in synaptic inputs and neuropeptide activation from afferent neurons. The functional importance of this maturation could be a pre-requisite for puberty onset. However, the mechanisms behind these dynamic changes have yet to be identified.<p cla...

Introduction: Estrogens play an essential role in reproduction and their peripheral action is mediated via nuclear alfa and beta receptors (ER) as well as membrane receptors. To date, only 3 females and 2 males from 3 families with a loss of function of ERa have been reported. The phenotype in these families was strongly suggestive of an estrogen resistance with an absence of a complete puberty, a delay in epiphyseal maturation with high estradiol levels and e...

Background: Mirror movements (MM) are frequently associated to Kallmann syndrome (KS). They are mainly observed in patients with ANOS1 (KAL1) mutations. MM have never been reported in ANOS1 mutated females. A defect in the contralateral inhibition of the pyramidal tract has been proposed as the mechanism of MM in KS but never demonstrated.Objective and hypotheses: To investigate the molecular mechanism of a familial case of gonadotropic deficiency in whi...

Background: Non-idiopathic central precocious puberty (CPP) is caused by acquired or congenital hypothalamic lesions visible on magnetic resonance imaging (MRI), or associated with various complex genetic and/or syndromic disorders without visible lesions on MRI. We investigated the different types and prevalences of non-isolated CPP phenotypes in a large group of consecutive patients with CPP.Methods: This observational cohort study included all patient...