ESPE Abstracts

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 ...

Inflammation is a known feature of Down syndrome (DS) and is caused by a dysregulation between pro and anti-inflammatory cytokines. Hashimoto's thyroiditis (HT) is characterised by a slowly developing persistent inflammation of the thyroid gland which frequently leads to hypothyroidism. In DS children, HT is the most common autoimmune disease ad its prevalence has been reported to be more elevated than that generally seen in age-matched patients without DS: 34% vs 1.3%, r...

Loss of function mutations in SGPL1 (sphingosine-1-phosphate lyase) are associated with a syndromic form of primary adrenal insufficiency. A third of affected male individuals also have evidence of early primary gonadal insufficiency, with an undervirilised phenotype at birth. SGPL1 carries out irreversible breakdown of the signalling molecule sphingosine-1-phosphate (S1P) and deficiency leads to accumulation of S1P and other upstream sphingolipid intermediates to var...

Introduction: The substantial increase in prevalence of childhood obesity presents a major challenge. Obesity is associated with significant physical and mental co-morbidities including diabetes and cardiovascular disease. Successful treatment requires intensive input from a specialist multidisciplinary team. In 2019, NHS England initiated a pilot to treat Complications Relating to Excess Weight (CEW) in dedicated clinics across the country. Facilitating suffi...

Introduction: Brain tumors are the most common solid neoplasm in children, and treatment often includes high-dose irradiation of the central nervous system (CNS). Although not universal, growth hormone deficiency (GHD) is a very common endocrine late effect after CNS irradiation in childhood. The consequences of GHD in adults are many e.g., reduced bone mineral density, fatigue, decreased lean body mass and adiposity, which implies that adults with severe GHD ...

Background: Children conceived after assisted reproductive technology (ART) with frozen embryo transfer (FET) are more often born large-for-gestational age (LGA) while children born after fresh embryo transfer (fresh-ET) are at risk of being small-for-gestational age (SGA). LGA or SGA children are at increased risk of obesity, diabetes and cardiovascular disease later in life. The long-term cardio-metabolic health of children born after ART is scarcely explore...

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:...

Background: Mounting evidence points to an association between increased glucocorticoid (GC) action and weight gain. However, the response to GCs is not only determined by GC serum concentrations, but also by individual differences in tissue-specific sensitivity, influenced by genetic and acquired (e.g. disease-related) factors. The extent to which differences in GC sensitivity may influence development of (abdominal) obesity, or vice versa, is poorly understo...

Objectives: We describe 5 pedigrees with a novel phenotype including GHD associated with primary ovarian insufficiency (POI) and investigate the underlying molecular basis.Patients and Methods: 6 Turkish patients (5F, 1M) born to 5 consanguineous pedigrees with severe GHD were identified. All females had POI; the male had normal puberty. All had severe postnatal growth retardation (height -4.4 to -8.9 SDS at presentation...

Introduction: The degree of consistency between the findings from next generation sequencing (NGS) and detailed endocrine assessment is unclear in boys with XY DSD.Objectives: Examine the range of endocrine and molecular genetic variation in boys undergoing evaluation for XYDSD.Methods: Boys with XYDSD who were evaluated in Glasgow from 2016 to 2018 were included. Sequence variants...