ESPE Abstracts

Background: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterised by ACTH resistance and leads to isolated glucocorticoid deficiency. Mutations in the gene encoding the ACTH receptor (MC2R) are responsible for around 25% of cases.Case report: The female index case was hyperpigmented at birth. At one week of age her ACTH level was >1200 ng/ml, plasma renin activity (PRA) 11.4 pmol/ml/h with an aldosterone of 520...

Background: The children and teenage diabetes team currently care for 270 patients in the region and includes speciality doctors, specialist nurses, dieticians and psychologists.Objective and null hypothesis: To evaluate the strengths and weaknesses of the local care provided by the team, and learn from current patient experience.Method: An anonymous questionnaire was completed by diabetic patients aged 9–20 years when attendi...

Introduction: Bloom syndrome (BS) is a rareautosomal recessive disorder caused by mutations in the BLM gene, located on the long arm of the chromosome 15 (15q26.1). The typical symptoms of the disease are short stature, low birth weight, dysmorphic features including long, narrow face (dolichocephaly), micrognathism and prominent nose and ears. Other characteristic features include a rash following sun exposure, hyper-pigmented areas or cafe-au-lait s...

Background: Beckwith-Wiedemann Syndrome (BWS) is a rare overgrowth disorder secondary to various mutations in growth-regulatory genes on chromosome 11p15.5. A well-established association exists between BWS and both benign and malignant tumours, most commonly Wilms’ tumour and hepatoblastoma. We present a less frequently described diagnosis of bilateral phaeochromocytoma in association with BWS.Case report: We report the case of a 14-year-old girl w...

Background: Pathogenic IGFI gene mutations causing childhood growth failure are rare. Only 5 autosomal recessive mutations, one IGFI copy number variant and 2 heterozygous frameshift mutations are reported. Heterozygous missense IGFI mutations have not previously been described.Objectives: To identify and functionally characterise a novel missense IGFI variant in a patient with postnat...

Background: Growth Hormone Insensitivity (GHI) is usually caused by mutations in the Growth Hormone receptor (GHR). Patients present with short stature associated with high GH and low IGF-I levels and often have midfacial hypoplasia (typical Laron syndrome facial features). Our centre previously described the first GHR pseudoexon mutation (42700896A>G, c. 618+792A>G). The inclusion of this 108bp pseudoexon is predicted to lead to in-frame insertion of...

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: 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:...

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...

Background: Noonan Syndrome (NS) can overlap clinically and biochemically with growth hormone insensitivity [GHI; short stature (SS), low IGF-I and normal/elevated GH levels]. Mutations in multiple genes regulating RAS/MAPK pathway have been identified in NS including LZTR1 variants. Function of LZTR1 is poorly understood and its role in growth retardation is unknown.Objectives: To functionally characte...