ESPE Abstracts

Introduction: The ZSWIM6 gene was first described with a unique de-novo heterozygous variant causing acromelic frontonasal dysostosis, characterized by craniofacial, brain, and limb malformations. Another de-novo heterozygous variant was later described causing severe intellectual disability, hypotonia amd seizures but without craniofacial or limb malformations. These findings suggest a clear genotype-phenotype correlation for ZSWIM6. Gene in...

Background: The underlying pathogenic mechanisms governing growth restriction of Noonan syndrome (NS) remain elusive. Monoallelic inactivating LZTR1 gene variants have been implicated as a cause of NS due to hyperactivation of the canonical RAS-MAPK signalling pathway. Missense LZTR1 variants have been associated with defective ubiquitination theoretically leading to increased Ras substrate availability. Ubiquitination is implicated in growth...

Background: Monosomy × (45,X) is associated with Turner syndrome (TS) and pregnancy loss; however, the underlying mechanisms remain unclear. Girls and young women with TS/45,X can present with diverse clinical features and at different ages, including early postnatal life, suggesting that at least some mechanisms may be defined during early fetal development.Aims: To explore transcriptomic expression profiles in ke...

Background and aims: Disparities in children's height often reflect socio-economic inequalities. Our aims were: (A) to describe anthropometric and socio-demographic data of children with short stature (CDC based height-z score<-2SDS) at age 6-7 years, compared to peers with height-z score≥-2SDS. (B) To assess risk factors for short stature at age 6-7 years based on growth and socio-demographic data at age 0-2 years.Met...

Objectives: Vosoritide is a C-type natriuretic peptide (CNP) analog that binds its receptor on chondrocytes, promoting growth by inhibiting the ERK1/2-MAPK pathway. We previously reported the results of a Phase II study in children with hypochondroplasia. Vosoritide led to an average increase in annualized growth velocity (GV) of 1.81 cm/year and gain of 0.36 in height SD over 12 months. We present here the pharmacokinetic/ pharmacodynamic (PK/PD) data from th...

Background: Severe primary insulin-like growth factor-1 deficiency (SPIGFD) is a rare growth disorder characterised by extreme short stature, low serum IGF-1 and normal/elevated serum growth hormone (GH). Some patients receive GH treatment before recombinant human IGF-1 (rhIGF-1; Increlex® [mecasermin]). We investigated rhIGF-1 effectiveness and tolerability in patients previously treated with GH versus GH naïve patients at rhIGF-1 initiati...