Endocrine Abstracts

Introduction: The UK 100,000 Genomes Project (100KGP) investigated the genetic basis of rare disease. The molecular drivers of most paediatric pituitary disease remains unknown.Methods: Children with genetically unexplained pituitary disorders attending a tertiary paediatric endocrinology centre were recruited to the 100KGP and underwent whole genome sequencing. Parental DNA was obtained where feasible. Virtual gene panels were applied and bioinformatic ...

Introduction: Coffin-Siris Syndrome (CSS) is a rare multisystem genetic disorder which often arises from genetic abnormalities within genes encoding for the SWI/SNF complex (ARID1A, ARID1B, DPF2, SMARCA4, SMARCB1, SMARCA2, SMARCE1). Endocrine abnormalities previously associated with this disorder include idiopathic short stature, hyperinsulinism, obesity, growth hormone deficiency, and cryptorchidism. We describe the endocrine features and associated radiological find...

Background: Septo-optic dysplasia (SOD) is a rare congenital condition diagnosed in children with two or more of hypothalamo-pituitary axis dysfunction, midline brain abnormalities, and optic nerve hypoplasia. SOD has a heterogenous clinical phenotype, characterised by varying visual impairment and endocrine dysfunction. Autistic-like behaviours have also been reported in children with SOD, however the nature of these neurobehavioural impairments remain to be fully understood....

Background: Silver-Russell syndrome (SRS) is a unique disorder characterised by characteristic features and growth restriction due to 11p15 LOM or upd(7)Mat in ~60% cases. Monogenic defects are a rare cause of SRS and HMGA2 mutations have been identified in 4 cases to date. The function of HMGA2 is poorly understood.Objectives: Assess the clinical phenotypes of 6 new patients with novel heterozygous HMGA2 defects and evaluate t...

Background: Pubertal progression is inhibited in central precocious puberty with the use of gonadotropin releasing hormone (GnRH) analogues. They are usually given every 10 to 12 weeks via an intramuscular depot, but more recently, a 6-monthly preparation has become available for clinical use.Aim: The aim of this project was to evaluate the efficacy and acceptability of 6-monthly triptorelin, a GnRH analogue, at a tertiary children’s hospital.<p...

Background: Pathogenic IGFI gene mutations causing childhood growth failure are extremely rare. Only five autosomal recessive mutations, one IGFI copy number variant and two heterozygous frameshift mutations are reported. Heterozygous missense IGFI mutations haven’t previously been described.Objectives: To identify and functionally characterise a novel missense IGFI variant in a patient with postnatal growth failu...