ISSN 1662-4009 (online)

ey0015.12-13 | New treatments | ESPEYB15

12.13 Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children with Heterozygous Familial Hypercholesterolemia: The CHARON Study (Hypercholesterolemia in Children and Adolescents Taking Rosuvastatin Open Label)

M Braamskamp , G Langslet , BW McCrindle , D Cassiman , GA Francis , C Gagne , D Gaudet , KM Morrison , A Wiegman , T Turner , E Miller , DM Kusters , JS Raichlen , PD Martin , EA Stein , JJP Kastelein , BA Hutten

To read the full abstract: Circulation 2017;136:359-366The National Heart, Lung and Blood Institute Panel on integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents recommended a universal screening approach that would include one-time testing of all children aged 9-11 years for dyslipidemia. This recommendation has raised controversy regarding t...

ey0020.1-14 | Pediatric Thyroid Cancer | ESPEYB20

1.14. Longitudinal analysis of cancer risk in children and adults with germline PTEN variants

L Yehia , G Plitt , AM Tushar , J Joo , CA Burke , SC Campbell , K Heiden , J Jin , C Macaron , CM Michener , HJ Pederson , K Radhakrishnan , J Shin , J Tamburro , S Patil , C Eng

Brief summary: PTEN hamartoma tumor syndrome is one of five well known genetic syndromes associated with differentiated thyroid carcinoma (1,2). PTEN hamartoma tumor syndrome comprises four different entities: Cowdwn syndrome, Bannayan-Riley-Ruvalcaba syndrome, PTEN-related Proteus syndrome, and Proteus-like syndrome caused by mutations in the PTEN (phosphatase and tensin homologue) tumor suppressor gene [3]. This prospective longitudinal mu...

ey0020.3-5 | Advances in Clinical Practice | ESPEYB20

3.5. High bone mass disorders: New insights from connecting the clinic and the bench

DJM Bergen , A Maurizi , MM Formosa , GLK McDonald , A El-Gazzar , N Hassan , ML Brandi , JA Riancho , F Rivadeneira , E Ntzani , EL Duncan , CL Gregson , DP Kiel , MC Zillikens , L Sangiorgi , W Hogler , I Duran , O Makitie , W Van Hul , G Hendrickx

In Brief: This comprehensive review classifies the known high bone mass (HBM) disorders based on Gene Ontology (GO) nomenclature. The authors emphasize the importance of functional genomics in the discovery of new HBM genes and discuss strategies to improve understanding of the underlying pathogenic mechanisms and inform the development of therapeutic approaches.Commentary: HBM disorders are typically defined by a high areal bone marrow density (BMD) <em...

ey0020.4-2 | Sexuality, Fertility and Fertility Optimization in DSD | ESPEYB20

4.2. Generation of functional oocytes from male mice in vitro

K Murakami , N Hamazaki , N Hamada , G Nagamatsu , I Okamoto , H Ohta , Y Nosaka , Y Ishikura , TS Kitajima , Y Semba , Y Kunisaki , F Arai , K Akashi , M Saitou , K Kato , K Hayashi

Brief summary: This in vitro study reports that fully potent oocytes were generated from pluripotent stem cells of the tail of a sexually mature male mouse. These oocytes were able to give rise to offspring after fertilization.A particular challenge in the care of DSD patients in adulthood is the optimization of fertility potential. Fertility outcome is significantly reduced in all types of DSD depending on the underlying etiology as well as the...

ey0020.5-12 | Basic Research | ESPEYB20

5.12. Defective jagged-1 signaling affects GnRH development and contributes to congenital hypogonadotropic hypogonadism

L Cotellessa , F Marelli , P Duminuco , M Adamo , GE Papadakis , L Bartoloni , N Sato , M Lang-Muritano , A Troendle , WS Dhillo , A Morelli , G Guarnieri , N Pitteloud , L Persani , M Bonomi , P Giacobini , V Vezzoli

Brief summary: Using a combination of expression studies in human embryos as well as functional studies in zebrafish and genetic sequencing of patient with congenital hypogonadotropic hypogonadism, this study identified a novel role for Jag1/Notch signaling in the development of GnRH neurons.GnRH neurons have a unique characteristic as they start life in the olfactory placode and then migrate into the hypothalamus during embryonic development, thanks to ...

ey0020.6-6 | Clinical Trials – New Treatments | ESPEYB20

6.6. Crinecerfont, a CRF1 receptor antagonist, lowers adrenal androgens in adolescents with congenital adrenal hyperplasia

Newfield Ron S , Sarafoglou Kyriakie , Fechner Patricia Y , Nokoff Natalie J , Auchus Richard J , Vogiatzi Maria G , Jeha George S , Giri Nagdeep , Roberts Eiry , Sturgeon Julia , Chan Jean L , Farber Robert H

Brief summary: This study evaluated the safety, tolerability and efficacy of Crinecerfont, a CRF1R antagonist in adolescents with classic congenital adrenal hyperplasia (CAH).Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is characterized by impaired cortisol synthesis and excess adrenal androgen secretion. Sufficient suppression of adrenal andogen production in classic CAH may be difficult with current formulations...

ey0020.8-2 | Clinical Trials – New Treatments | ESPEYB20

8.2. Closed-loop therapy and preservation of C-peptide secretion in type 1 diabetes

CK Boughton , JM Allen , J Ware , ME Wilinska , S Hartnell , A Thankamony , T Randell , A Ghatak , REJ Besser , D Elleri , N Trevelyan , FM Campbell , J Sibayan , P Calhoun , R Bailey , G Dunseath , R Hovorka , CLOuD Consortium

Brief summary: In this multicenter, open-label, parallel-group, randomized trial, 97 adolescents (aged 10–16.9 years) were randomized within 21 days after the diagnosis of type 1 diabetes (T1D) to receive either hybrid closed-loop therapy or standard insulin therapy (control) for 24 months. Although closed-loop therapy was associated with better glycemic outcomes, there were no differences in C-peptide between the two groups.The Closed Loop from Ons...

ey0020.10-1 | New Data on the Epidemiology of T2D in Children | ESPEYB20

10.1. Trends in incidence of youth-onset type 1 and type 2 diabetes in the USA, 2002-18: results from the population-based SEARCH for Diabetes in Youth study

LE Wagenknecht , JM Lawrence , S Isom , ET Jensen , D Dabelea , AD Liese , LM Dolan , AS Shah , A Bellatorre , K Sauder , S Marcovina , K Reynolds , C Pihoker , G Imperatore , J Divers , SEARCH for Diabetes in Youth Study Divers

Brief summary: The incidences of T1D and T2D in children and young people increased in the USA over the last 2 decades. For the first time, the incidence of T2D has surpassed that of T1D.Comment: The SEARCH study has served as a national resource to explore the epidemiology and consequences of diabetes in the US. Published over the years, the findings contribute to understanding future trends in other parts of the world. Overall, the current report shows...

ey0020.13-4 | Section | ESPEYB20

13.4. Evolution of the germline mutation rate across vertebrates

LA Bergeron , S Besenbacher , J Zheng , P Li , MF Bertelsen , B Quintard , JI Hoffman , Z Li , J St Leger , C Shao , J Stiller , MTP Gilbert , MH Schierup , G Zhang

In Brief: The authors conducted genome sequencing on 151 mother–father–offspring trios from 68 vertebrate animal species in order to estimate and compare germline mutation rates (GMRs). They found a 40-fold variation in GMR per generation between the species. Higher GMRs were observed in species that have a longer generation time, older age at puberty and fewer offspring per generation.Comment: Mutations in germline DNA during gametogenesis are...

ey0020.13-12 | Section | ESPEYB20

13.12. Embryo model completes gastrulation to neurulation and organogenesis

G Amadei , CE Handford , C Qiu , J De Jonghe , H Greenfeld , M Tran , BK Martin , DY Chen , A Aguilera-Castrejon , JH Hanna , MB Elowitz , F Hollfelder , J Shendure , DM Glover , M Zernicka-Goetz

In Brief: The authors created mouse embryos in the laboratory from a combination of multiple stem cell lines. These embryos were developed ex vivo up to the equivalent of day 8.5 post-fertilization. Embryos developed within an extraembryonic yolk sac and were similar to whole natural embryos, with defined forebrain and midbrain regions, a beating heart-like structure, a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and also pr...