ESPE Abstracts

Introduction: Human growth is a multifactorial process involving genetic, hormonal, nutritional and environmental factors. Genome-wide association studies (GWAS) have shown that >400 genes are associated with adult height. African Baka Pygmies represent an isolated and well-confined small population with short stature of unknown etiology. In previous studies we reported an 8-fold reduced GH receptor gene expression and reduced serum levels of IGF-I and GHB...

Background: Approximately 10% of children born small for gestational age (SGA) fail to catch-up nd remain short (SGA-SS). Although several mechanisms causing SGA-SS have been elucidated, the primary cause remains speculative in most cases.Aim: To decipher genetic causes of SGA-SS defined as birth length and/or birth weight <-2 SD for gestational age, and body height <-2.5 SD after the 3rd year of life within a larg...

Introduction: Familial short stature (FSS) describes vertically transmitted growth disorders. Traditionally, polygenic inheritance is presumed, but monogenic inheritance seems to occur more frequently than expected. Clinical predictors of monogenic FSS have not been elucidated thus far. The aim of the study was to identify the monogenic etiology and its clinical predictors in FSS children.Patients and Methods: Of 747 pat...

Introduction: The genetic investigation of tall stature (TS) is routinely indicated only in children with clinical suspicion of a specific syndrome associated with TS. After ruling out an endocrine disorder, the remaining tall children mostly receive a clinical diagnosis of “idiopathic” (ITS) or “familial” tall stature (FTS). The aetiology of their TS remains unknown.Aims: To elucidate genetic cau...

Introduction: The diagnosis of growth hormone deficiency (GHD) is complex, involving the combination of auxological, laboratory, and radiological findings. This includes growth hormone (GH) stimulation tests, which are done to confirm the diagnosis. It has been discussed that these tests have low specificity, potentially leading to false positive results. Therefore, children with GHD are regarded as a heterogeneous group with varied causes of short stature. Ne...

Introduction: C-type natriuretic peptide receptor encoded by NPR2 gene stimulates chondrocyte differentiation and hypertrophy and extracellular matrix production within the growth plate. The phenotypical spectrum of NPR2 mutations is broad, from severe autosomal recessive acromesomelic dysplasia to milder autosomal dominant growth disorders. Some children with NPR2 variants are treated with growth hormone (GH), however, with the inco...

Introduction: Ox in a dose of 0.03-0.05 mg/kg per day in addition to GH treatment significantly increases adult height in TS more than GH alone. To date, the long term effects of Ox in childhood on bone mineral density (BMD) in adulthood are unknown.Methods: This is a follow-up study of a previous randomized controlled trial, performed in the Netherlands. In the original trial, 133 girls were treated with GH. Placebo (Pl...

Background: Children born small for gestational age (SGA) exhibit wide variations in the activity of growth hormone (GH)/insulin–like growth factor–I (IGF-I) axis and this heterogeneity may result in supra physiological concentrations of IGF-I during GH treatment. The long-term effects of elevated IGF-I levels has been a matter of concern. We explored the variations in total IGF-I and bioactive IGF-I and the associations with growth and glucose metab...

Objective: Merge and standardize the scarce data on molecular and phenotypic findings of mutations in the human leptin receptor (LEPR) gene causing a rare form of severe early-onset obesity.Methods: We summarized functional and phenotypic traits of LEPR mutations reported in the literature in a structured and comprehensive manner. Additional data was obtained from 6 subjects of our outpatient clinic not reported so far. Functionality of mutations was ass...

Introduction: Congenital central hypothyroidism (CCH) is a rare disease with inappropriate thyroid hormone secretion due to impaired TSH stimulation. TSH levels are not elevated; the patients are not diagnosed in TSH-based newborn screening. Biallelic variants in TRHR gene (encoding TRH receptor) are one of four genetic defects known to cause isolated CCH (THRH, THSB, IGSF1, TBL1X). The phenotype is variable but generally mild (neon...