Searchable abstracts of presentations at key conferences in endocrinology

ea0056p726 | Clinical case reports - Pituitary/Adrenal | ECE2018

A family with Kallmann syndrome due to a novel FGFR1 mutation

Martins Ana Sousa , Gregory Louise , Dattani Mehul

Introduction: Kallmann syndrome (KS) is a developmental disorder characterised by hypogonadotropic hypogonadism and anosmia. Known genetic causes account for up to 30% of patients with KS, with FGFR1 mutations being identified in 10%. FGFR1-related KS has an autosomal dominant inheritance with incomplete penetrance. We present a family with KS due to a novel variably penetrant FGFR1 mutation, where the presenting features included cleft lip/palate and anosmia...

ea0039oc6.2 | Oral Communications 6 | BSPED2015

Mutations in BRAF are associated with septo-optic dysplasia and cardiofaciocutaneous syndrome

Gregory Louise , Besser Rachel , Temple Karen , Davies Justin , Dattani Mehul

Background: Mutations in BRAF are a rare cause of cardiofaciocutaneous syndrome (CFC). Recently, BRAF mutations have been reported in papillary craniopharyngiomas, but have not been described in patients with other hypothalamo-pituitary abnormalities. We describe three patients with CFC and septo-optic dysplasia (SOD) associated with heterozygous BRAF mutations.Cases: Patients presented in childhood with clinical features of ge...

ea0036P76 | (1) | BSPED2014

Septo-optic dysplasia, multiple pituitary hormone deficiency and optic nerve hypoplasia: clinical and neuroradiological characteristics

Guemes Maria , Cerbone Manuela , Kasia Tessa , Gregory Louise , Dattani Mehul

Introduction: Multiple pituitary hormone deficiency (MPHD) and septo-optic dysplasia (SOD) are well known causes of hypopituitarism, but children with optic nerve hypoplasia (ONH) may also be at risk of hormone and neurocognitive disturbances. Clinical and neuroradiological findings of these three related conditions are characterised in this study, aiming to understand their pathophysiology.Design: Data from 140 patients with hypopituitarism (MPHD, SOD) ...

ea0027oc1.7 | Oral Communications 1 | BSPED2011

Mild GH deficiency due to two novel homozygous mutations in the gene encoding GHRH receptor (GHRHR) in a single family

Gregory Louise C , Alatzoglou Kyriaki S , Dattani Mehul T

Introduction: Release of GH by the somatotroph cells of the anterior pituitary is stimulated by GHRH. GHRH acts via its transmembrane receptor, GHRHR, a G-protein coupled receptor that stimulates protein kinase A. Recessive mutations in GHRHR are associated with severe isolated GH deficiency (IGHD) with a final height in untreated patients between 130±10 cm (−7.2±1.6 SDS) and 114±0.7 cm (−8.3±0.1 SDS) in males and females respectively.</p...

ea0027p19 | (1) | BSPED2011

Mutations in the Sonic Hedgehog signalling pathway in patients with congenital hypopituitarism

Gregory Louise C , Webb Emma A , Panagiotakopoulos Leo , Dattani Mehul T

Introduction: The Gli-family of zinc-finger transcription factors regulates the Sonic Hedgehog (Shh) signalling pathway, critical for normal CNS development. Gli2 is essential for early pituitary and ventral forebrain development in mice, with mutations described in humans with holoprosencephaly (HPE), isolated hypopituitarism (HP) and cranial/midline facial defects. SHH mutations have been associated with phenotypes including HPE but not HP, despite murine studi...

ea0085p41 | Pituitary and Growth 1 | BSPED2022

Use of the U.K. 100,000 genomes project to identify the genetic basis of childhood pituitary disorders within a tertiary paediatric endocrinology centre

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

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 ...

ea0033oc2.7 | Oral Communications 2 | BSPED2013

Novel lethal form of hypopituitarism associated with the first recessive LHX4 mutation

Gregory Louise C , Rhodes Simon J , Levy Miles J , Greening James , Humayun Khadija , Dattani Mehul T

Background: LHX4 encodes a member of the LIM-homeodomain transcription factor protein family that is required for development of the pituitary gland. To date, only incompletely penetrant heterozygous mutations in LHX4 have been described in patients with variable combined pituitary hormone deficiencies (CPHD).Objective/hypothesis: To investigate a cohort of patients with congenital hypopituitarism for mutations in LHX4.<p c...

ea0027p24 | (1) | BSPED2011

A case of familial isolated hypogonadotrophic hypogonadism due to FGFR1 G687R mutation

Tziaferi Vaitsa , Spoudeas Helen , McCabe Mark , Gregory Louise , Dattani Mehul T

Introduction: Hypogonadotrophic hypogonadism (HH) is a genetically heterogeneous disorder. A number of genes have been implicated in its pathogenesis but, to date, in most cases, the cause remains genetically unknown.Case: A 14-year old male with delayed puberty (G1P2A3, testes two males) and family history of HH was diagnosed with HH following anterior pituitary assessment and an overnight gonadotrophin profile. His baseline gonadotrophins were low (LH,...

ea0027p18 | (1) | BSPED2011

Novel KAL1 mutations associated with septo-optic dysplasia in three female patients

McCabe Mark , Gregory Louise , Hu Youli , Thankamony Ajay , Hughes Ieuan , Townshend Sharron , Bouloux Pierre-Marc , Dattani Mehul

Introduction: KAL1 is essential for GnRH neuronal migration and olfactory bulb development, and mutations within this gene have been implicated in 5% of Kallmann syndrome (KS) cases, a disorder characterized by the association of hypogonadotrophic hypogonadism with anosmia. It is the only identified X-linked form of the disorder and as a result only KS males had been screened for mutations until recently, when females exhibiting KS phenotypes were screened and subsequen...

ea0050oc5.6 | Reproduction and Neuroendocrinology | SFEBES2017

The MAPK effector B-Raf is essential for hypothalamic–pituitary axis development and activating mutations in BRAF cause congenital hypopituitarism

Kyprianou Nikolina , Gregory Louise , Lillina Vignola Maria , Besser Rachel , Marinelli Eugenia , Gualtieri Angelica , Scagliotti Valeria , Davis Shannon , Gevers Evelien , Dattani Mehul , Gaston-Massuet Carles

Somatic activating mutations in BRAF, encoding B-Raf, have been described in tumours and recently craniopharyngiomas. Germline mutations in BRAF and other components of the RAS/MAPK pathway are found in RASopathies, whose features include endocrine deficiencies but not craniopharyngiomas. We report three BRAF mutations (two of which are novel) in four children with congenital hypopituitarism. To demonstrate the functional role of the three variants w...