hrp0094p2-280 | Growth and syndromes (to include Turner syndrome) | ESPE2021

Outcomes in growth hormone-treated Noonan syndrome children: impact of PTPN11 mutation status

AL Jorge Alexander , Pietropoli Alberto , Kelepouris Nicky , Horikawa Reiko ,

Objectives: Mutations in PTPN11 are known to be associated with Noonan syndrome (NS), accounting for approximately 50% of cases. Data from a non-interventional and phase 3 study of Norditropin (somatropin; Novo Nordisk A/S, Denmark) were used to assess the impact of PTPN11 mutation status on growth outcomes in children with NS receiving growth hormone therapy (GHT).Methods: The ANSWER (NCT01009905) prog...

hrp0086fc6.5 | Syndromes: Mechanisms and Management | ESPE2016

Pathogenic Copy Number Variants are Frequently Identified in Children with Short Stature of Unknown Etiology

Canton Ana , Homma Thais , Furuya Tatiane , Roela Rosimeire , Arnhold Ivo , Jorge Alexander

Background: The etiology of short stature is heterogeneous, often encompassing complex genetic disorders of difficult diagnosis. Analysis of chromosomic copy number variants (CNVs) has been demonstrating the important role of these genomic imbalances in population diversity and human disease.Objective and hypotheses: To analyze the frequency and describe novel submicroscopic chromosomal CNVs in a group of patients with short stature of unknown cause....

hrp0084p3-944 | GH & IGF | ESPE2015

The Impact of GH Therapy in Noonan Syndrome Children with Identified Mutations in RAS/MAPK Pathway

Malaquias Alexsandra , Moraes Michelle , Funari Mariana , Pereira Alexandre , Bertola Debora , Jorge Alexander

Objective: To evaluate the response to recombinant human GH (rhGH) treatment in NS children with short stature and previously identified mutations in the RAS/MAPK pathway genes.Methods: 23 patients with NS (17 males; 19 PTPN11, 3 RAF1 e 1 SHOC2) were daily treated with rhGH (mean rhGH dose of 47 μg/kg per day). The main outcome measures were 1st year growth velocity, change in height SDS (Noonan syndrome specifi...

hrp0094p2-381 | Pituitary, neuroendocrinology and puberty | ESPE2021

Characterization of puberty development in a large cohort of patients with Noonan syndrome with molecular diagnosis

Rezende Raissa , Jorge Alexander , Noronha Renata , Keselman Ana , Andrade Nathalia , Dantas Naiara , Bertola Debora , Malaquias Alexsandra ,

Introduction: Noonan syndrome (NS) is a relative frequent genetic disorder, mainly characterized by dysmorphic face features, congenital heart defects and short stature. Though delayed pubertal development has been described in both sexes, the physiopathological root remains unclear. This study aims at characterizing puberty development in Noonan syndrome.Materials and Methods: The study population included 111 individuals with a molecul...

hrp0092rfc8.4 | Pituitary, Neuroendocrinology and Puberty Session 1 | ESPE2019

Evaluation of Puberty in Patients with Noonan Syndrome and Mutations in the RAS/MAPK Genes

Malaquias Alexsandra C. , Noronha Renata M , Homma Thais K , Albuquerque Edoarda V A , Bertola Debora R , Jorge Alexander A L

Background: Noonan syndrome (NS) is a rare genetic disease characterized by facial dysmorphism, short stature, heart defects, chest deformities, and variable developmental delay/learning disabilities. Almost 80% of patients have a mutation in the genes encoding components of the RAS/MAPK pathway. Puberty was described as delayed in NS patients, but few studies are focusing on this subject and genotype-phenotype correlations so far.<s...

hrp0089fc15.4 | Growth and Syndromes | ESPE2018

The Metabolic Profile Associated with RASopathies

Noronha Renata , Homma Thais , Moraes Michelle , Albuquerque Edoarda , Funari Mariana , Pereira Alexandre , Villares Sandra , Bertola Debora , Jorge Alexander , Malaquias Alexsandra

Background: Noonan syndrome (NS) is a frequent autosomal dominant disorder characterized by facial dysmorphisms, heart defects, short stature and learning disabilities. It is caused by mutations in genes within the RAS/MAPK signaling pathway, thus called RASopathies. The RAS/MAPK pathway can also impact the signal transduction of hormones involved in body weight, carbohydrate, and lipid metabolism features scarcely studied only in animal models. This study aimed to describe me...

hrp0086fc7.6 | Gonads &amp; DSD | ESPE2016

Whole-Exome Sequencing Reveals RAD51B Variant in Two Sisters with Primary Ovarian Failure

Franca Monica , Funari Mariana , Nishi Mirian , Domenice Sorahia , Latronico Ana Claudia , Jorge Alexander , Lerario Antonio , Mendonca Berenice

Background: Primary ovarian failure (POF) is a major cause of female infertility. POF is characterized by amenorrhea, hypo-estrogenism and elevated gonadotrophin levels. In POF disorder, several genetic alterations have been described, however in most of the patients the etiology of this disorder remains unknown.Objective and hypotheses: To identify new genes implicated in the development of POF using Next-Generation Sequencing (NGS).<p class="abstex...

hrp0086rfc6.2 | Syndromes: Mechanisms and Management | ESPE2016

RAB3IP and DGCR8 as a Potentially Pathogenic Novel Candidate Gene Involving in Growth Disorders

Homma Thais , Funari Mariana , Lerario Antonio , Freire Bruna , Nishi Mirian , Yamamoto Guilherme , Naslavsky Michel , Zatz Mayana , Arnhold Ivo , Jorge Alexander

Background: The majority of children with short stature are classified as idiopathic short stature. Whole exome sequencing can help identify genetic causes of short stature.Methods: We recruited 10 children with short stature of unknown etiology. We conducted whole exome sequencing of the patients and their family members. We used an analysis pipeline to identify rare nonsynonymous genetic variants that might cause the short stature. All rare allelic var...

hrp0089rfc9.1 | Pituitary, Neuroendocrinology and Puberty 1 | ESPE2018

Clinical and Genetic Features of Central Precocious Puberty Associated with Complex Phenotypes

Canton Ana , Brito Vinicius , Montenegro Luciana , Ramos Carolina , Macedo Delanie , Bessa Danielle , Cunha Marina , Jorge Alexander , Mendonca Berenice , Latronico Ana Claudia

Background: Idiopathic central precocious puberty (CPP) is mostly described as an isolated entity. A few studies have shown its association with clinical syndromes and rare cases of chromosomal abnormalities.Objective: To clinically characterize patients with CPP, pointing out prevalent associated conditions and phenotypes.Patients and Methods: One hundred and forty-five patients with idiopathic CPP were retrospectively evaluated. ...

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...