hrp0094p2-308 | Growth and syndromes (to include Turner syndrome) | ESPE2021

Evidence that non-syndromic familial tall stature has an oligogenic origin including ciliary genes

Weiss Birgit , Eberle Birgit , Roeth Ralph , de Bruin Christiaan , Lui Julian C , Paramasivam Nagarajan , Hinderhofer Katrin , van Duyvenvoorde Hermine A , Baron Jeffrey , Wit Jan M , Rappold Gudrun A ,

Human growth is a complex trait. A considerable number of gene defects have been shown to cause short stature, but there are only few examples of genetic causes of non-syndromic tall stature. Besides rare variants with large effects and common risk alleles with small effect size, oligogenic effects may contribute to this phenotype. Exome sequencing was carried out in a tall male (height 3.5 SDS) and his parents. Filtered damaging variants with high CADD scores were validated b...

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...

hrp0097rfc4.4 | Growth and syndromes (to include Turner syndrome) | ESPE2023

Genetic findings in short Turkish children born to consanguineous parents

Joustra Sjoerd , Isik Emregul , M. Wit Jan , Catli Gonul , Anik Ahmet , Haliloglu Belma , Kandemir Nurgun , Ozsu Elif , Hendriks Yvonne , de Bruin Christiaan , Kant Sarina , Campos-Barros Angel , Challis Rachel , Parry David , Harley Margaret , Jackson Andrew , Losekoot Monique , van Duyvenvoorde Hermine

Objective: To describe clinical, laboratory and genetic characteristics of 42 short children from 34 consanguineous Turkish families.Design: Descriptive case series.Methods: After collecting clinical information, DNA samples were analysed in three European laboratories. In 18 children (12 families) suspected of a genetic defect in the growth hormone (GH)-insulin-like growth factor ...

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...