hrp0095p1-143 | Pituitary, Neuroendocrinology and Puberty | ESPE2022

Use of the 100,000 Genomes Project to identify the molecular basis of rare endocrine disorders within a tertiary paediatric endocrinology centre

M McGlacken-Byrne Sinead , Gregory Louise , Roberts Rowenna , Wakeling Emma , Katugampola Harshini , T Dattani Mehul

Introduction: The UK 100,000 Genomes Project (100KGP) recently investigated the genetic basis of rare disease using whole genome sequencing. The genetic aetiology of most rare paediatric endocrine disease remains unexplained.Methods: Children with genetically unexplained rare endocrine disease attending a subspecialist paediatric endocrinology clinic underwent whole genome sequencing as part of the 100KGP. Parental DNA w...

hrp0097fc12.1 | Thyroid | ESPE2023

Graves’ disease – are we just delaying the inevitable?

Stevens Chloe , Langham Shirley , Amin Rakesh , T Dattani Mehul , E Brain Caroline , J Peters Catherine

Background: The incidence of Graves’ disease in patients aged <15 years is estimated at 0.9 per 100,000. Parental anxiety around definitive treatment, timing of this around schooling and clinician confidence in long-term medical treatment often results in prolonged medical management. This audit aimed to assess the rates of remission, timing of definitive treatment and long-term medical management in children managed for Graves’ at a UK tertiary...

hrp0097rfc13.6 | Pituitary, neuroendocrinology and puberty 2 | ESPE2023

Pituitary size on volumetric MRI predicts the severity of the neuroendocrine phenotype in populations at risk

Cerbone Manuela , D'Arco Felice , A Spoudeas Helen , Clark Chris , T Dattani Mehul

Background: Hypopituitarism in children is a complex condition and its hierarchical evolution at different developmental windows is unpredictable. Magnetic resonance imaging (MRI) is helpful but largely a subjective assessment of anomalies of the hypothalamo-pituitary (H-P) structures. We aimed to test the utility of a quantitative measure of pituitary and stalk in predicting neuroendocrine phenotypes.Patients and Methods:</stron...

hrp0097p1-145 | Pituitary, Neuroendocrinology and Puberty | ESPE2023

Novel clinical and imaging tools to identify and grade hypothalamic disease in populations at risk

Cerbone Manuela , D'Arco Felice , A Spoudeas Helen , Clark Chris , T Dattani Mehul

Background: Hypothalamic dysfunction (HD) is life-threatening but precise diagnostic tools are lacking. Normal hypothalamic anatomy is difficult to delineate on MRI. Damage to the area is inferred from a visible lesion, but how widely it disturbs signalling connections or correlates with symptoms is unclear. Furthermore, in congenital/syndromic diseases the hypothalamus appears normal even in cases with clear HD. We aimed to develop novel clinical and radiolog...

hrp0095p1-371 | Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology | ESPE2022

Exome sequencing reveals a high proportion of causal and candidate gene variants in a large early-onset Primary Ovarian Insufficiency cohort

M McGlacken-Byrne Sinead , P Suntharalingham Jenifer , Ishida Miho , Buonocore Federica , Del Valle Ignacio , Cameron-Pimblett Antoinette , Genomics UCL , T Dattani Mehul , S Conway Gerard , C Achermann John

Background: The presentation of early-onset Primary Ovarian Insufficiency (EO-POI), most often with primary amenorrhea, is at one end of a spectrum spanning 40 years. The aetiology of POI is frequently unclear but next generation sequencing of varied age groups has identified several associated genetic variants. Whether girls with EO-POI are more likely to have a genetic aetiology than those with later presentations remains unknown.<stro...

hrp0097rfc10.4 | Fetal, neonatal endocrinology and metabolism (to include hypoglycaemia) &amp; Multisystem endocrine disorders | ESPE2023

Clinical phenotypes of a multicentric cohort of ROHHAD patients

Napoli Flavia , Cerbone Manuela , Guftar Shaik M , Buonocore Federica , Angelelli Alessia , Fava Daniela , Tuli Gerdi , Pistorio Angela , T Dattani Mehul , Maghnie Mohamad

Background: ROHHAD syndrome (rapid-onset obesity with hypothalamic dysfunction, central hypoventilation, autonomic dysregulation) – also defined as ROHHADNET when associated with neural tumors - is a rare condition with a high mortality rate. The aim of this study is to describe the phenotypes of a multicentric cohort of ROHHAD patients.Patients and Methods: We retrospectively analyzed clinical data from 22 patient...

hrp0095rfc5.5 | Adrenals and HPA Axis | ESPE2022

Mosaic PRKACA duplication causing a novel and distinct phenotype of early-onset Cushing syndrome and acral cutaneous mucinosis

M McGlacken-Byrne Sinead , Abdelmaksoud Ashraf , Haini Mohammad , Palm Liina , Ashworth Michael , Li Juan , Wang Wei , Wang Xiumin , Wang Jian , Callaghan Bridget , A Kinsler Veronica , Faravelli Francesca , T Dattani Mehul

Introduction: Genetic alterations within the cAMP/PKA pathway, including the genes GNAS, PDE11A, PDE8, PRKAR1A/B, and PRKACA, result in a spectrum of adrenocortical disorders. To date, somatic PRKACA variants and germline PRKACA copy number gain have been associated with the development of cortisol-secreting adrenocortical adenomas and bilateral adrenal hyperplasia, respectively. While variants within the PRKAR1A ge...

hrp0097fc7.2 | Sex differentiation, gonads and gynaecology or sex endocrinology | ESPE2023

Mapping the transcriptomic landscape of early human fetal ovary development through a clinically-focused lens

M McGlacken-Byrne Sinead , Del Torres Ignacio , P Suntharalingham Jenifer , Buonocore Federica , HDBR ICH , Crespo Berta , Moreno Nadjeda , C Simcock Ian , Arthurs Owen , Xenakis Theodoros , Niola Paola , Brooks Tony , T Dattani Mehul , C Achermann John

Introduction: Ovary development was once considered a largely passive process. RNA sequencing (RNAseq) approaches have allowed us to begin to characterise ovary development in previously unparalleled detail, revealing the process to be complex and, still, little understood. A challenge is synthesising and using these data to advance our understanding of clinical disease. Through a clinically-focused lens, we elucidate novel aspects of the transcriptional lands...