hrp0092p1-223 | Growth and Syndromes (to include Turner Syndrome) (1) | ESPE2019

Tall Stature and Macrodactyly of the Great Toes Due to a Novel Mutation in the Natriuretic Peptide Receptor-2 Gene

Lauffer Peter , van Duyvenvoorde Hemine , van Haeringen Arie , van der Kaay Danielle

Background: Mutations in the gene encoding the natriuretic peptide receptor-2 gene (NPR2) are responsible for monogenic growth disorders. Loss-of-function variants cause extreme short stature and skeletal dysplasia. Gain-of-function mutations cause tall stature with - in some cases - macrodactyly of the great toes, a Marfanoid habitus, arachnodactyly and scoliosis. We describe a novel gain-of-function mutation in exon 8 of NPR2 in a family wi...

hrp0084p1-163 | Miscelleaneous | ESPE2015

Paediatric Thyroid Nodule Score: Derivation and Validation of a Predictive Score for Thyroid Nodule Assessment in Children

van der Kaay Danielle , Wasserman Jonathan , Akseer Nadia , Roskies Michael , Liberte Frederique la , Nguyen Lily , Puligandla Pramod

Background: Differentiated thyroid carcinoma has an incidence of 15.2 per 100 000 in adolescents. The clinical challenge is identifying nodules requiring further intervention. Current modalities, in isolation, have poor ability to reliably differentiate benign from malignant nodules.Objective and hypotheses: To derive and validate a predictive score that integrates clinical, laboratory, radiological and cytopathological parameters to define malignancy ri...

hrp0084p3-942 | GH & IGF | ESPE2015

Long-Term Insulin Sensitivity and β-Cell Function in Short Children Born Small for Gestational Age Treated with GH and GnRHa: Results of a Randomised, Dose-response Trial

van der Steen Manouk , Lem Annemieke J , van der Kaay Danielle C M , Hokken-Koelega Anita C S

Background: Pubertal children born small for gestational age (SGA) with a poor adult height (AH) expectation can benefit from treatment with GH 1 mg/m2 per day (~0.033 mg/kg per day) in combination with 2 years of GnRH analogue (2 years GnRHa) and even more so with 2 mg/m2 per day (~0.067 mg/kg per day). Concerns haven been raised about the effects of GH and GnRHa on insulin sensitivity on the long-term.Objective and hypotheses: To ...

hrp0094p1-129 | Growth A | ESPE2021

Computer-aided facial analysis as a tool to identify patients with Silver-Russell syndrome and Prader-Willi syndrome

Ciancia Silvia , Goedegebuure Wesley J. , Grootjen Lionne N. , Hokken-Koelega Anita C.S. , Kerkhof Gerthe F. , van der Kaay Danielle C. ,

Introduction: Genetic syndromes often show suggestive facial features that provide clues for the diagnosis. Considering the high number of genetic syndromes and the possible overlap of some features, memorizing facial gestalt is a challenging task for clinicians. DeepGestalt technology, and its app Face2Gene, has a growing impact on the diagnosis and management of genetic diseases by analyzing the features detected in one or more facial images of affected indi...

hrp0097p1-127 | Growth and Syndromes | ESPE2023

Effects and safety of growth hormone (GH) treatment in 6 children with pycnodysostosis

Renes Judith , Sas Theo , Clement-de Boer Agnes , Zwaveling-Soonawala Nitash , van der Kaay Danielle , Hokken-Koelega Anita

Background: Pycnodysostosis is a very rare autosomal recessive skeletal dysplasia caused by cathepsin K deficiency. It is characterized by extreme short stature resulting in an adult height in males typically <150 cm and in females <134 cm. Bone-fragility and frequent fractures are present. There are few case-reports on the effects of GH treatment.Objective: To evaluate the effect and safety of GH in 6 patients wit...

hrp0097fc11.2 | GH and IGFs | ESPE2023

Clinical characteristics of heterozygous ACAN gene variants and longer-term response to growth hormone treatment: real-world data

Renes Judith , Reedijk Ardine , Losekoot Monique , Kant Sarina , van der Steen Manouk , van der Kaay Danielle , Hokken-Koelega Anita , van Duyvenvoorde Hermine , de Bruin Christiaan

Background: Heterozygous pathogenic variants in the ACAN gene underlie disproportionate short stature with characteristically accelerated bone age (BA) maturation and/or osteochondritis dissecans (OD)/early-onset osteoarthritis (OA).Objective: To describe the phenotypic spectrum and assess the response and safety of growth hormone (GH) treatment in children with a heterozygous pathogenic ACAN variant.</...

hrp0097p1-119 | Growth and Syndromes | ESPE2023

Clinical features and response to rhGH treatment in ten patients with heterozygous IGF1 variants

Punt Lauren , van der Kaay Danielle , van Setten Petra , Bocco Gianni , de Munnik Sonja , Losekoot Monique , van Duyvenvoorde Hermine , de Bruin Christiaan , Maarten Wit Jan , Joustra Sjoerd

Introduction: Patients carrying homozygous IGF1 loss-of-function mutations are extremely rare and show severe pre- and postnatal growth failure, microcephaly, developmental delay, retrognathia and sensorineural deafness. Heterozygous variants in IGF1 appear to be more common in short stature, but only few cases have been reported in detail. Therefore, clinical features and growth response to recombinant human growth hormone (rhGH) therapy are...

hrp0097fc4.3 | Growth and syndromes (to include Turner syndrome) | ESPE2023

Pathogenic variants in GHSR cause short stature and growth hormone neurosecretory dysfunction; results from a large case series

Punt Lauren , Kooijman Sander , van der Kaay Danielle , van Tellingen Vera , Bakker - van Waarde Willie , Boot Annemieke , van den Akker Erica , van Boekholt Anneke , van Duyvenvoorde Hermine , van Nieuwaal - Van Maren Nancy , Woltering Claire , Heijligers Malou , van der Heyden Josine , Bannink Ellen , Losekoot Monique , de Bruin Christiaan , Maarten Wit Jan , Joustra Sjoerd

Introduction: Ghrelin binds to its receptor GHSR1A, encoded by GHSR, on somatotrophs of the pituitary. Growth hormone (GH) secretion is enhanced by ghrelin binding as well as the receptor’s constitutive activity. Results from in vitro experiments, knock-out mice, and GWAS suggest that heterozygous loss-of-function of GHSR may be associated with short stature, but observations in case studies are equivocal. We aimed to better ch...

hrp0097p1-318 | Growth and Syndromes | ESPE2023

15-year experience with the IGF1 generation test in the Netherlands

Kruijsen Anne , de Groote Kirsten , Punt Lauren , van Trotsenburg Paul , Pijnenburg-Kleizen Karijn , Bocco Gianni , Berkenbosch Lizanne , van Setten Petra , Claahsen - van der Grinten Hedi , van der Kaay Danielle , Schott Nina , van Tellingen Vera , van Mill Edgar , van der Heyden Josine , Brandsma Annelies , Hendriks Yvonne , Losekoot Monique , van Duyvenvoorde Hermine , Hokken-Koelega Anita , Renes Judith , Maarten Wit Jan , de Bruin Christiaan , Joustra Sjoerd

Introduction: Among children with short stature, some show persistent IGF-I levels <-2.0 SDS despite a normal growth hormone (GH) response in a stimulation test. This may be caused by conditions that could benefit from recombinant human GH (rhGH) therapy (e.g. GH neurosecretory dysfunction, bioinactive GH, partial GH insensitivity). Therefore, the IGF-I generation test (IGFIGT) was implemented in 2006 using a national, standardized protocol. Children with a...

hrp0097p1-507 | Growth and Syndromes | ESPE2023

Identification and characterisation of novel HMGA2 variants expand the clinical spectrum of Silver-Russell syndrome

Vickram Maharaj Avinaash , Cottrell Emily , Thanasupawat Thatchawan , D. Joustra Sjoerd , Triggs-Raine Barbara , Fujimoto Masanobu , G. Kant Sarina , van der Kaay Danielle , Clement-de Boers Agnes , Brooks A.S. , Amador Aguirre Gabriel , Martín del Estal Irene , Inmaculada Castilla de Cortázar Larrea María , Massoud Ahmed , A. Van Duyvenvoorde Hermine , De Bruin Christiaan , Hwa Vivian , Klonisch Thomas , Hombach-Klonisch Sabine , L. Storr Helen

Background: Silver Russell syndrome (SRS) is a heterogeneous disorder characterised by intrauterine and post-natal growth retardation, relative macrocephaly, protruding forehead, feeding difficulties and body asymmetry. Variants in HMGA2 are a rare cause of SRS and despite strong evidence for the crucial role of HMGA2 in growth regulation, its functional role in human linear growth is unclear.Methods: Patients w...