hrp0089fc4.4 | GH & IGFs | ESPE2018

A Cross-Sectional Study of IGF-I Bioavailability Through Childhood and Associations with PAPP-A2, STC2 and Anthropometric Data

Fujimoto Masanobu , Khoury Jane , Andrew Melissa , Hwa Vivian , Dauber Andrew

Background: Insulin-like growth factor I (IGF-I) is one of the important hormonal mediators of human growth. Circulating IGF-I exists in a ternary complex bound to the acid-labile subunit (ALS) and one of its six binding proteins (BPs). IGF-I bound to ALS and BPs needs to be liberated by either Pregnancy Associated Plasma Protease A (PAPP-A) or A2 (PAPP-A2) to reach its receptor. Stanniocalcin 2 (STC2) is a potent inhibitor of both PAPP-A and PAPP-A2. Genome-wide association s...

hrp0089p3-p214 | GH & IGFs P3 | ESPE2018

Two Siblings with Short Stature

V Sri Nagesh , Dauber Andrew , Kanithi Ravishankar , Dutta Deep , G Ram Kumar

2 siblings were referred for evaluation fo short stature and failure to thrive. Both were born of 3rd degree consanguinity, first and second in birth order. the first sibling was 2 1/2 year old at time of referral and had birthweight of 3.1 kg and had gross motor delay. Present height was 65 cm (SDS −6.2 S.D.)and weight was 6 kg (<3rd centile) Second sibling was 1.5 years old, with gross motor delay with height of 57 cm (SDS −6.5 S.D.</sma...

hrp0086fc8.3 | Growth: Clinical | ESPE2016

PAPP-A2 Gene Mutation Effects on Glucose Metabolism and Bone Mineral Density and Response to Therapy with Recombinant Human IGF-I

Salcedo Catalina Cabrera , Hwa Vivian , Tyzinski Leah , Andrew Melissa , Wasserman Halley , Backeljauw Philippe , Dauber Andrew

Background: PAPP-A2 (pregnancy-associated plasma protein A2) deficiency, caused by homozygous mutations in the PAPP-A2 gene results in a novel syndrome of significant growth failure. PAPP-A2 cleaves IGF binding proteins 3 and 5, thereby freeing IGF-I from its ternary complex and allowing it to become biologically active. We recently reported the first two families with PAPP-A2 mutations. Response to recombinant human IGF-I (rhIGF-1) in these patients is unknown.<p class="a...

hrp0086rfc6.6 | Syndromes: Mechanisms and Management | ESPE2016

Growth Hormone (GH) Deficiency Type II: Clinical and Molecular Evidence of Impaired Regulated GH Secretion Due to an Gln181Arg GH-1 Gene Mutation

Miletta Maria Consolata , Eble Andree , Arnhold Ivo J P , Dauber Andrew , Fluck Christa , Pandey Amit

Background: Main features of the autosomal dominant form of GH deficiency (IGHD II) include markedly reduced secretion of GH combined with low concentrations of IGF-I leading to short stature.Objective and hypotheses: We report on a girl referred for assessment of short stature (−4.6 SDS) at a chronological age of 7 yr 10 mo. The GH deficiency was confirmed by standard GH provocation tests, which revealed severely reduced GH and IGF-I concentration...

hrp0086rfc14.3 | Growth : Mechanisms | ESPE2016

Whole Exome Sequencing Identifies a GH1 Gene Mutation Causing Familial Isolated Growth Hormone Deficiency with Normal Peak Growth Hormone Concentrations

Salcedo Catalina Cabrera , Hwa Vivian , Tyzinski Leah , Andrew Melissa , Backeljauw Philippe , Dauber Andrew

Background: Familial isolated growth hormone deficiency (IGHD) type II is autosomal dominantly inherited and caused by splice-site mutations and nucleotide substitutions in the GH1 gene. The missense mutation R183H is a well-described genetic variant that causes familial IGHD type II. Individuals with this mutation have releasable GH stores, but GH secretion is severely reduced resulting in short stature.Objective and hypotheses: This study aimed to repo...

hrp0084p2-462 | Growth | ESPE2015

Advanced Bone Age and Accelerated Dental Development Associated with Elevated Retinoic Acid Levels and Haploinsufficiency of CYP26A1 and CYP26C1

Nilsson Ola , Isoherranen Nina , Guttmann-Bauman Ines , Jee YouHee , Guo Michael , Lui Julian , Dauber Andrew

Background: Nutritional excess of vitamin A, a precursor for retinoic acid (RA), causes premature epiphyseal fusion, craniosynostosis, as well as light-dependent retinopathy. Similarly, homozygous loss-of-function mutations in one of the major RA-metabolizing enzymes CYP26B1 causes advanced bone age, premature epiphyseal fusion, and craniosynostosis. We studied a patient with markedly accelerated skeletal and dental development, retinal scarring, and autism-spectrum disease.</...

hrp0095p1-307 | Growth and Syndromes | ESPE2022

A Prospective Clinical Trial of Vosoritide in Hypochondroplasia: Baseline Demographics and Preliminary Results

Dauber Andrew , McCarthy Tara , Zhang Anqing , Merchant Nadia , Boucher Kimberly , Dham Niti , Kanakatti Shankar Roopa

Objectives: Vosoritide is a C-type natriuretic peptide analog which binds its receptor on chondrocytes, leading to increased chondrocyte proliferation and differentiation via its inhibition of the ERK1/2-MAPK pathway. It was recently approved for increasing linear growth in children with achondroplasia. This is the first study to examine the safety and efficacy of vosoritide in children with hypochondroplasia.Methods: Th...

hrp0082fc4.4 | Growth | ESPE2014

Short Stature, Accelerated Bone Maturation, and Early Growth Cessation due to Heterozygous Aggrecan Mutations

Nilsson Ola , Guo Michael , Dunbar Nancy , Popovic Jadranka , Flynn Daniel , Jacobsen Christina , Lui Julian , Hirschhorn Joel , Baron Jeffrey , Dauber Andrew

Background: Most children with idiopathic short stature (ISS) have a delayed bone age (BA). ISS with advanced BA is far less common. We studied three families with autosomal dominant short stature, unexplained BA acceleration, and premature growth cessation.Objective and hypotheses: To identify the genetic cause of this condition and describe its clinical spectrum.Method: Whole exome sequencing was performed in selected individuals...

hrp0089p1-p177 | Growth &amp; Syndromes P1 | ESPE2018

Genetic Investigation of Children with Syndromic Prenatal Onset Short Stature

Homma Thais , Freire Bruna , Ronjo Rachel , Dauber Andrew , Funari Mariana , Lerario Antonio , Arnhold Ivo , Canton Ana , Sugayama Sofia , Bertola Debora , Kim Chong , Malaquias Alexsandra , Jorge Alexander

Background: Patients born small for gestational age (SGA) with additional syndromic features to short stature are likely to present with genetic causes.Aim: To perform a clinical and genetic-molecular investigation of a group of syndromic SGA patients without catch-up growth.Methods: We selected 118 patients born SGA [birth weight and/or length standard deviation score (SDS) ≤−2 for gestational age] without catch-up gro...

hrp0089fc9.1 | Pituitary, neuroendocrinology and Puberty 1 | ESPE2018

Novel Variants in the POU1F1 Beta Isoform are Associated with Isolated Growth Hormone Deficiency and Combined Pituitary Hormone Deficiency

Hoppmann Julia , Rockstroh-Lippold Denise , Gergics Peter , Nakaguma Marilena , Carvalho Luciani Renata Silveira , Pfaeffle Heike , Jamra Rami Abou , Jorge Alexander , Guo Michael H. , Dauber Andrew , Keller Eberhard , Camper Sally A. , Arnhold Ivo JP , Pfaeffle Roland

Background: Hypopituitarism is characterized by deficiency of one or more anterior pituitary hormones. POU1F1 mutations are the second most frequent known cause of combined pituitary hormone deficiency (CPHD). Patients are typically deficient in GH, TSH, and prolactin, although two unrelated cases were reported with isolated GH deficiency (IGHD). To date, all POU1F1 mutations have been reported for the predominantly expressed alpha isoform, which is a transcr...