hrp0086fc9.1 | Pathophysiology of Disorders of Insulin Secretion | ESPE2016

Next Generation Sequencing for the Diagnosis of Monogenic Diabetes in Switzerland

Klee Philippe , Dirlewanger Mirjam , Blouin Jean-Louis , Castellsague-Perolini Montserrat , Santoni Federico , Schwitzgebel Valerie

Background: Monogenic diabetes (MD) remains undiagnosed in more than 90% of the cases. However, precise, quick and cost-effective diagnosis is important to choose an adequate treatment and to avoid long-term complications.Objective and hypotheses: To develop and validate a diagnostic tool to improve diagnosis rate of MD in Switzerland, as well as to open new research directions.Method: Targeted next-generation sequencing (NGS) of 3...

hrp0086p1-p239 | Diabetes P1 | ESPE2016

Fetal Growth Restriction Due to Maternal Congenital Hyperinsulinism Associated with a Novel Variant in GLUD1 and Intrauterine Diazoxide Exposure

Dirlewanger Mirjam , Klee Philippe , Ranza Emmanuelle , Gastaldi Giacomo , Boulvain Michel , Schwitzgebel Valerie M

Background: Congenital hyperinsulinism (CHI) is a rare disease mostly due to loss-of-function mutations of the ABCC8 or KCNJ11 genes, encoding the two subunits of the KATP channel. Gain-of-function mutations in glutamate dehydrogenase 1, encoded by the GLUD1 gene, are the second most common cause of CHI.Objective and hypotheses: The majority of patients with a GLUD1 CHI respond to diazoxide, but little is kn...

hrp0082p1-d1-58 | Diabetes | ESPE2014

A leu402pro Mutation of the Non-hla Gene il18rap in Aggressive Neonatal Type 1 Diabetes Mellitus

Dirlewanger Mirjam , Blouin Jean-Louis , Bevillard Jeremy , Santoni Federico , Schwitzgebel Valerie

Background: Neonatal diabetes mellitus is defined by severe hyperglycemia appearing before 6 months of age. It occurs in about one in 200 000 live births and most cases are known to be of monogenic origin. Classical autoimmune type 1 diabetes mellitus (DM) is exceptional in this age group.Objective and hypotheses: Recently non-HLA type 1 DM susceptibility genes, such as IL18RAP, influencing the rate of progression to diabetes among children with...

hrp0084p1-33 | Diabetes | ESPE2015

Improved Genetic Testing for Monogenic Diabetes in the Swiss Population by Targeted Next Generation Sequencing

Dirlewanger Mirjam , Blouin Jean-Louis , Klee Philippe , Castellsague-Perolini Montserrat , Girardin Celine , Santoni Federico , Schwitzgebel Valerie

Background: Monogenic diabetes is a heterogeneous group of diabetes due to a single gene mutation and includes neonatal diabetes (NDM), MODY and rare forms of syndromic diabetes. These forms of diabetes remain undiagnosed in probably more than 90% of patients. The aim of the study was to identify mutations causing monogenic diabetes using a single test.Method: Swiss endocrinologists were proposed to participate in the study and to send blood samples of t...

hrp0084p1-96 | Growth | ESPE2015

Ligase IV Deficiency Syndrome as a Cause of Microcephalic Primordial Dwarfism in Dizygotic Twins

Girardin Celine , Ranza Emmanuelle , Klee Philippe , Dirlewanger Mirjam , Caflisch Marianne , Bottani Armand , Schwitzgebel Valerie

Background: Microcephalic primordial dwarfism (MPD) is a group of rare genetic disorders defined by severe growth restriction of both prenatal and postnatal weight (W), height (H), and particularly head circumference (HC).Objective and hypotheses: To elucidate the genetic origin of the MPD in dizygotic twins.Method: Exome sequencing of 19 genes known to be implicated in microcephaly was performed.Results: Diz...

hrp0094p2-449 | Thyroid | ESPE2021

Congenital multinodular goiter causing acute airway obstruction in a newborn: a case report

Mirjam Scheffer-Rath , Katharina Löhner , Nitash Zwaveling-Soonawala , Boot Annemieke

Introduction: Multinodular goiter is an extremely rare condition in neonates and can account for tracheal airway compression.Case report: A newborn girl presented immediately after birth with an inspiratory and expiratory stridor and a visible swelling in the neck. She was born term after an uneventful pregnancy with a birth weight of 3.26 kg. The mother had no known thyroid disease and had not used antithyroid or goitrogenic medication. She had a normal...

hrp0084p1-52 | Diabetes | ESPE2015

A Randomised Trial of the Effects of Perinatal Education of Overweight Pregnant Women to Prevent Childhood Overweight: The ETOIG Study

Parat Sophie , Cosson Emmanuel , Baptiste Amandine , Tauber Marie-Therese , Valensi Paul , Bertrand Anne-Marie , Dabbas Myriam , Elie Caroline , Lorenzini Francoise , Negre Veronique

Background: Early-life risk factors of childhood obesity include maternal obesity; smoking, diabetes and high weight gain during pregnancy for the mother; short duration of breastfeeding and poor quality of early feeding in the infants. Perinatal life thus may be a good period for primary prevention.Objective and hypotheses: We aimed to evaluate whether perinatal education of overweight pregnant women would reduce childhood overweight.<p class="abste...

hrp0092p1-270 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology (1) | ESPE2019

Large Spectrum of DSD Phenotype Caused by Pathogenic Variants in Wilms Tumor Suppressor Gene 1

Ferrari Maria Tereza Martins , Domenice Sorahia , Mendonça Berenice Bilharino , Moraes Daniela Rodrigues , Batista Rafael Loch , Gomes Nathalia Lisboa , Nishi Mirian Yumie , Sircili Maria Helena , Paula Tatiana Evelin , Costa Eduardo , Costa Elaine Maria Frade

Introduction: The Wilms tumor suppressor gene 1 (WT1) plays an essential role in urogenital and kidney development. Heterozygous germline mutations in WT1 have been classically associated with Denys–Drash (DDS) and Frasier syndrome (FS). Exonic missense mutations in the zinc-finger region are the cause of DDS and mutations affecting the canonic donor KTS splice site of intron 9 are the cause of FS. New phenotypes, as 46,XX testicular DSD...

hrp0092p3-219 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

Final Adult Height in SRY-Negative 46,XX Ovotesticular Differences of Sex Development Individuals

Martins Ferrari Maria Tereza , Moraes Rodrigues Daniela , Lisboa Gomes Nathalia , Yumi Nishi Mirian , Loch Batista Rafael , Maria Frade Costa Elaine , Bilharinho Mendonca Berenice , Domenice Sorahia , Marques Cruz Patricia Sales , Sircili Maria Helena

Introduction: Differences of sex development (DSD) encompass a variety of conditions with atypical development of chromosomal, gonadal or anatomic sex. 46, XX ovotesticular (OT) DSD is a rare condition, in which the presence of testicular and ovarian tissues is identified in the same individual. These patients present variable phenotypes with a wide spectrum of atypical genitalia and their sex assignment can be male or female. Short stature is a frequent issue...

hrp0089p2-p263 | Growth &amp; Syndromes P2 | ESPE2018

Genetic Investigation of SHORT Stature: A Case Report of Complex Constitutive Rearrangement Involving Chromosome 15

Pinto Renata Machado , Minasi Lysa Bernardes , Pinto Irene Plaza , Silva Juliana Ferreira da , Cunha Damiana Mirian da Cruz , Ribeiro Cristiano Luiz , Silva Claudio Carlos da , Cruz Aparecido Divino da

Introduction: Growth is a complex process influenced by several genetic factors both pre and postnatal, in which 80% of the height variation is explained by genetic factors. Nevertheless, the standard medical evaluation of short stature (SS) relies upon physical examination and laboratory parameters and identifies a pathological cause of SS in 1–40% of individuals. Rearrangements affecting chromosome 15 are rare and affected patients show a variety of nonspecific features...