Endocrine Abstracts

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell-clusters of normal adrenals could suggest the existence of co-driver mutations which influence the development or phenotype of APAs [1]. Gain-of-function mutations in both CTNNB1 and the G-protein coupled receptor GNA11 were found by whole exome sequencing in 3/10 APAs. Further sequencing of...

A 7.7 year old girl born to consanguineous was assessed for poor growth; height −3.2 SDS, weight −2.7 SDS, BMI −0.8 SDS. Examination revealed chubby cheeks, abdominal obesity, relatively thin limbs and a suggestion of mid-face hypoplasia. There was no scoliosis or other dysmorphic features.Investigations found a 46XX karyotype and negative coeliac screen. Pituitary function testing revealed high basal Growth Hormone (GH) of 6.5 ug/l, ri...

Case report: An 11-year-old boy presented with an increasingly waddling gait and backache. He had been born small for gestational age (BW 1.8kg; -4.7 SDS) and had a history of dyspraxia and autism. He reported reasonable dairy intake and had no history of previous fractures or clinical signs of osteogenesis imperfecta (OI). Spinal imaging revealed multiple vertebral fractures. Malignancy and systemic inflammatory causes were excluded. An OI gene panel revealed a single pathoge...

Background: Silver-Russell Syndrome (SRS) is a clinically and genetically heterogenous condition. 40% patients with ‘clinical’ SRS remain without a genetic diagnosis despite fulfilling the Netchine-Harbison Clinical Scoring System (NH-CSS) criteria. There is increasing recognition of the wide range of clinical phenotypes within the SRS spectrum and overlap with other short stature syndromes.Methods: We analysed 26 undiagnosed patients with feat...

Section 1: Case history: A 10-year-old girl presented with significant postnatal growth failure. Her birth weight was normal (–0.15SDS) but poor growth was observed from a few months of age. She had no other symptoms. On examination, height was –3.4SDS and head circumference –1.6SDS. She had no dysmorphic features and normal development. Section 2: Investigations: Baseline serum analyses were unremarkable. Karyotype was normal (46XX). Bone age was delayed by 2.5...

Background: Silver Russell syndrome (SRS) is a heterogeneous disorder characterised by intrauterine and post-natal growth retardation, relative macrocephaly, protruding forehead, feeding difficulties and body asymmetry. Variants in HMGA2 are a rare cause of SRS and despite strong evidence for the crucial role of HMGA2 in growth regulation, the underlying mechanism underlying growth retardation has, thus far, not been elucidated....

Introduction: Bloom syndrome (BS) is a rare autosomal recessive disorder caused by mutations in the BLM gene. Classic dysmorphic features include a long, narrow face, micrognathism and prominent nose and ears. Other features of the disease include pre- and post-natal growth failure, skin rash following sun exposure, hyper-pigmented areas or cafe-au-lait lesions, high-pitched voice and immunodeficiency. The most serious complication of BS is the significant increase in...

Background: Growth hormone insensitivity (GHI) is a continuum defined by normal/elevated growth hormone (GH), low IGF-I levels and growth restriction. Non-classical/mild-moderate GHI is poorly characterised and is frequently underdiagnosed. Heterozygous dominant negative (DN) gene variants located in the regions encoding the intracellular/transmembrane domains of the GH receptor cause a ‘non-classical’ GHI phenotype.Hypothesis/Objective: Detail...

Case history: Two unrelated male patients were referred for evaluation of short stature. The first patient aged 16.5 years, had a birth weight of 2.6 kg at term (BWSDS -2.4), height 153 cm (HSDS -3.2) at referral and normal BMI SDS of 0.6. He had early postnatal hypoglycemia, which was conservatively managed, but no other significant clinical history. He had relative macrocephaly and disproportionate short stature. His mother was also short with a similar phenotype (height 147...

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...