ESPE Abstracts

Background: Germline mutations in SDHB gene are associated with the familial paraganglioma (PGL) syndrome that carries the highest malignant potential. Although penetrance is lower than initially described, lack of effective treatments for metastatic PGLs makes screening essential for early tumour detection, surgical removal and improved outcome. However, no consensus exists in relation to timing and mode of screening.Objective: To assess publis...

Background: Adults have a weight that is normal for them. This is referred to as their ‘set-point’ for weight. Studies have shown physiological protection of this set-point, explaining why most obese adults who diet eventually regain weight.Objective and hypotheses: We hypothesised that set-points for weight, and their physiological defence, are flexible in childhood but become fixed sometime around puberty. We aimed to show that obese children...

Background: The human foetal adrenal (FA) undergoes vast physiological changes as pregnancy progresses. Original descriptions of FA development emerged following morphometric studies from spontaneous/medical terminations. These revealed the greatest increase in FA size was during the first trimester. Recently, sonographic evaluation of human FA volume and length has led to the creation of normal FA growth centiles and correlations between FA size and estimated foetal weight (E...

Background: Adrenal Insufficiency (AI) is a heterogeneous diagnosis comprising multiple central and peripheral causes. The unifying feature is the requirement for glucocorticoid replacement and subsequent risk of life-threatening Adrenal Crisis (AC) and Adrenal Death (AD). Very few studies have investigated rates of AD in children. Multiple studies have reported symptoms of children with AC as interpreted by medical staff but no studies have looked at parental...

Background: Growth hormone insensitivity (GHI) encompasses normal/elevated growth hormone (GH), low IGF-I levels and growth restriction. Non-classical/mild-moderate GHI is an emerging entity which is poorly characterised, and, in many subjects, the underlying cause is unclear. Heterozygous dominant negative (DN) variants located in the intracellular/transmembrane domain of the GH receptor (GHR) cause a ‘non-classical’ GHI phenotype.<p class="abst...

Background: Noonan syndrome (NS) is caused by variants in multiple genes regulating the RAS/MAPK signalling cascade. NS can present with growth failure associated with growth hormone insensitivity (GHI; low IGF-I and normal/elevated GH levels). Variants in LZTR1 lead to NS, although the interaction of LZTR1 with the RAS/MAPK and the GH-IGF-1 pathways remain to be elucidated.Objectives: To gain insights into the ...

Background: Silver Russell syndrome (SRS) is genetically heterogenous and around 30% of patients with clinical SRS have no genetic diagnosis. Mutations in HMGA2 have recently been identified causing growth failure and an SRS-like phenotype. Despite strong evidence of the crucial role of HMGA2 in growth across species, the mechanism of action of HMGA2 in human linear growth is unclear.Objective:...

Context: Congenital hypothyroidism from thyroid dysgenesis (CHTD) is mainly a sporadic and non-syndromic condition occurring in 1:4,000 live births. In contrast to rare cases of syndromic monogenic CHTD, non-syndromic (NS) CHTD shows low familial recurrence risk (~2%) and low concordance rate between MZ twins, suggesting a two-hit scenario combining post-zygotic events with either a de novo monogenic mutation or incomplete penetrance of polyg...

Background: Thymus transplantation is undertaken for conditions associated with severe immunodeficiency. These comprise a number of genetic and syndromic associations including 22q deletion syndrome, CHARGE association, diabetic embryopathy, and other rarer conditions. Autoimmune thyroid dysfunctions (Hashimoto's thyroiditis and Graves' Disease) are described in the literature as the most common autoimmune disease after thymic transplant.<p class="...

Objectives: The homozygous GHR pseudoexon (6ψ) mutation leads to aberrant splicing of the GHR gene with clinical and biochemical heterogeneity. We investigated whether the phenotypic variability could be explained by transcript heterogeneity i.e. ratio of abnormal (6ψ GHR) to normal (WT GHR) transcripts and/or the presence of concurrent defects in other short stature (SS) genes.Methods: 6&#968...