ESPE Abstracts

Background: Hypothalamic-pituitary (HP) deficiencies are frequent in childhood brain tumor survivors (CBTS) after cranial radiation. There is currently no consensus on the most optimal way to screen for HP dysfunction regarding diagnostic tests or time interval. It is not known whether MRI changes in time in the HP-region or in brain volume are predictive of HP dysfunction.Aim: To quantify changes in the HP-region and in brain volume on MRI in CBTS after...

Background: Following the 2010 CAH consensus, the need for genetic confirmation of diagnosis remains uncertain and variation in practice is unclear.Methods: This variation was assessed by using the International CAH(I-CAH) Registry which was developed using the same platform as the I-DSD Registry.Results: After the development of the I-CAH Registry in October 2014, the rate of addition of CAH cases increased from 2/month to 14/mont...

Abnormal DNA methylation contributes to tumor progression and is emerging as a prognostic marker in several types of cancers. To investigate whether DNA methylation is associated with pediatric adrenocortical tumor (pACT) presentation and patient prognosis, we analyzed the methylation profile of 57 tumors (MethylationEPIC BeadChip Array-Illumina) and patients’ clinicopathological features and outcome. The study comprehended 40 girls and 17 boys, with median age at diagnos...

Background: ACH, the most common short-limbed skeletal dysplasia, is characterized by defective endochondral ossification resulting from gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene, a negative regulator of endochondral bone formation. Current treatment options are non-targeted, ineffective, or painful interventions aimed at preventing or treating complications. Infigratinib is an orally bioavailable and selective...

Background: ACH is the most common short-limbed skeletal dysplasia, affecting between 1 in 15,000 to 1 in 30,000 live births. Children and adults with ACH have disproportionate short stature, with a final height of approx. 131 cm for males and 124 cm for females. People with ACH are prone to significant co-morbidities, including obstructive sleep apnea, chronic otitis media with conductive hearing loss, spinal stenosis, and a propensity towards obesity. In som...

Introduction: Vosoritide increases growth in children with achondroplasia aged 5–18 years (Savarirayan et al, Genet Med, 2021). We recently reported results from a phase 2, randomized, double-blind, placebo-controlled study (111-206) in young children with achondroplasia aged 3 months–5 years Here we present results from an open-label extension study (111-208) spanning up to 4 years of treatment in the children aged 2-5 years at study star...

An oral GH secretagogue (GHS), LUM-201, stimulates GHSR-1a receptor to enhance endogenous GH pulsatile release. In moderate iPGHD, pulses of GH are found but at reduced levels, resulting in decreased IGF-1 and poor growth. The impact of LUM-201 on GH profiles during treatment of such children has not been reported.Objective: To characterize GH profiles, defined by deconvolution analysis, based on GH concentration in a time series and its...

Background: Achondroplasia (ACH), the most common short-limbed skeletal dysplasia, is characterized by impaired endochondral ossification resulting from gain-of-function pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3) gene, a negative regulator of endochondral bone growth. People with ACH are at risk for several significant co-morbidities, including brainstem compression due to foramen magnum stenosis, sleep-disordered breathing, chronic...

Background: Impairment of the chromatin remodeling factors ATRX and DAXX and telomeres abnormality play a role in cancer biology, influencing the clinical outcomes. However, their roles in adrenal tumorigenesis require broader investigation.Aim: To evaluate ATRX and DAXX genotype and expression, telomere length, and the alternative lengthening of telomeres (ALT), as well as their clinical significance, in primary adrenoc...

Aim: To uncover a feasible tumor expression prognostic signature and potential therapeutic targets for children with pACT.Methods: Tumor RNAseq from 53 pACT children (70% girls, median age: 1.7yrs) was performed (Illumina). Using a robust, state-of-the-art, differential gene expression analysis pipeline, differentially expressed genes (DEGs: adjusted P<0.05 and |log2 fold-change|>1) were identified (DESeq2...