Searchable abstracts of presentations at key conferences in endocrinology

ea0066oc4.5 | Oral Communications 4 | BSPED2019

Novel genetic defects in a cohort of Silver–Russell Syndrome (SRS) and SRS-like patients

Cottrell Emily , Ishida Miho , Moore Gudrun , Storr Helen L

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...

ea0074oc1 | Oral Communications | SFENCC2021

A rare heterozygous IGFI variant causing postnatal growth failure and offering novel insights into IGF-I physiology

Cottrell Emily , Chatterjee Sumana , Hwa Vivian , Storr Helen L.

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...

ea0078OC5.1 | Oral Communications 5 | BSPED2021

Evaluating UK Referral Criteria for Children with Short Stature in a Tertiary Paediatric Endocrinology Centre

White Gemma , Cosier Shakira , Andrews Afiya , Willemsen Ruben H. , Savage Martin O. , Storr Helen L.

Background: Childhood growth monitoring aims to identify growth failure and detect underlying pathology. According to UK guidance, height <-2.7 standard deviation score (SDS) (<0.4th percentile) is used as the referral threshold. Additional referral criteria include height deficit (HSDS-target height SDS) <-2.0 and height velocity (HV) SDS <-1.3. Lack of routine HV and mid-parental height calculation, combined with stricter cut-offs compared to other European c...

ea0051oc5.3 | Oral Communications 5 | BSPED2017

Novel evidence implies that ALADIN, the triple A syndrome gene product is involved in mitochondrial physiology

Da Costa Alexandra Rodrigues , Meimaridou Eirini , Prasad Rathi , Metherell Louise A. , Chapple J. Paul , Storr Helen L.

Triple A syndrome (AAAS), a rare and debilitating autosomal recessive disorder. It is characterised by adrenal failure, alacrima and achalasia; ~70% patients develop a neurodegeneration. The AAAS gene encodes ALADIN, a nuclear pore complex (NPC) protein necessary for the selective nuclear import of DNA protective molecules and is important for cellular redox homeostasis. ALADIN’s role is not fully characterised: its discovery at the centrosome and the endoplasmic...

ea0066oc2.2 | Oral Communications 2 | BSPED2019

A rare but very important cause of growth failure

Cottrell Emily , Ladha Tasneem , Borysewicz-Sańczyk Hanna , Sawicka Beata , Bossowski Artur , Storr Helen L

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...

ea0033oc1.9 | Oral Communications 1 | BSPED2013

Genetic characterisation of short children with potential defects of GH action by single gene sequencing

Kowalczyk Julia , Gevers Evelien F , Savage Martin O , Dunkel Leo , Metherell Louise A , Storr Helen L

Background: GH resistance or primary IGF1 deficiency (PIGFD) presents with growth failure, low serum IGF1 and normal/elevated serum GH. PIGFD comprises a spectrum of phenotypic and biochemical abnormalities for which genetic GH–IGF1 axis defects may be causative.Objective: Genotyping of PIGFD patients referred for sequencing of candidate genes.Methods: From 2008 to 2013, 62 patients (42 males and 20 females), median age 6.9 ye...

ea0045oc6.6 | Oral Communications 6- Endocrine | BSPED2016

Predictive factors of an underlying genetic defect in children with short stature and suspected growth hormone insensitivity (GHI)

Chatterjee Sumana , Shapiro Lucy , Davies Kate M , Savage Martin O , Metherell Louise A , Storr Helen L

Background: GH insensitivity (GHI) presents with growth failure, IGF-1 deficiency and normal/elevated GH (basal >5 μg/l and/or peak >10 μg/l). GHI encompasses a spectrum of clinical and biochemical abnormalities. Associations between phenotypic characteristics and genetic defects remain obscure.Objective: Identify phenotypic predictors of underlying genetic defects in GHI.Methods: In total of 102 children (62M) me...

ea0078OC6.1 | Oral Communications 6 | BSPED2021

Novel dominant negative GH receptor variants provide important insights into GH receptor physiology

Andrews Afiya , Cottrell Emily , Maharaj Avinaash , Ladha Tasneem , Williams Jack , Metherell Louise A , McCormick Peter J , Storr Helen L

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...

ea0082oc1 | Oral Communications | SFEEU2022

Genetic analysis of patients with undiagnosed short stature identified novel dominant negative GH receptor variants which provide important insights into GHR physiology

Andrews Afiya , Cottrell Emily , Maharaj Avinaash , Ladha Tasneem , Williams Jack , A Metherell Louise , J McCormick Peter , Storr Helen L

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...

ea0063p734 | Pituitary and Neuroendocrinology 2 | ECE2019

A phase 2 study assessing osilodrostat in children and adolescent patients with Cushing’s disease – Rationale and methods

Storr Helen L , Shah Nalini , Wojna Judi , Han Kevin , Roughton Michael , Pierre Combes Francois , Pultar Philippe , Savage Martin O

Background: In children, Cushing’s disease (CD) presents with a combination of weight gain and slowed linear growth. First-line pituitary surgery is the treatment of choice for most patients. In paediatric patients, the transsphenoidal surgical success rate is 60%–98% when performed by an expert pituitary surgeon. There is a need for additional pharmacological interventions to control hypercortisolaemia, which are currently limited, in children and adolescents. In ph...