hrp0097fc13.3 | Pituitary, neuroendocrinology and puberty 2 | ESPE2023

Variants in Methyl-CpG-binding protein 2 (MECP2) are associated with X-Linked Central Precocious Puberty

E Read Jordan , Guasti Leonardo , Paganoni Alyssa , Korbonits Marta , R Howard Sasha

Whilst several key genetic contributors to the phenotype of central precocious puberty (CPP) have been recognized, many familial cases remain without clear a genetic aetiology. Causal genetic variants are reported in imprinted genes Makorin ring finger protein 3 (MKRN3) and Delta-like homolog 1 (DLK1), alongside Kisspeptin-1 (KISS1) and (KISSR1), implicating mis-regulation of transcriptional control of the kisspeptin and GnRH neuroendocrine systems in onset of CPP. We recently...

hrp0097fc13.5 | Pituitary, neuroendocrinology and puberty 2 | ESPE2023

Systematic review and meta-analysis of spermatogenesis rates after pubertal induction with gonadotropins in males with hypogonadotropic hypogonadism

Alexander Emma , Ng Yin Kyla , Faruqi Duaa , Farquhar Robert , Unadkat Ayesha , Varughese Rachel , Howard Sasha

Background: Hypogonadotropic hypogonadism is characterised by inadequate secretion of gonadotropins (luteinising hormone (LH) and follicle-stimulating hormone (FSH)) leading to absent, partial or arrested puberty. In males, classical treatment with testosterone promotes virilisation but does not facilitate testicular growth and spermatogenesis. Conversely, treatment with gonadotropins or gonadotropin-releasing hormone (GnRH) stimulates Sertoli and Leydig cells...

hrp0098s12.3 | The impact of gonadotrophin dysregulation on neurocognition | ESPE2024

Studying the genetic interplay between GnRH deficiency and associated neurocognitive disorders by combining in silico, in vitro and in vivo tools.

Oleari Roberto , Lettieri Antonella , Amoruso Federica , Scheiffele Peter , Howard Sasha , Ruhrberg Christiana , Cariboni Anna

Gonadotropin releasing hormone (GnRH) neurons embryonically originate in nasal placode and migrate to hypothalamus, where they release GnRH to control reproduction. Defective GnRH neuron development or function leads to GnRH deficiency (GD), which is often associated to neurodevelopmental and neurological syndromes, including epilepsy, ataxia, intellectual disabilities and deafness. In addition, a register-based study showed correlation between delayed puberty and neurodevelop...

hrp0098p2-172 | Growth and Syndromes | ESPE2024

European Achondroplasia Forum: Are Current Outcome Measures for Achondroplasia Still Fit for Purpose in the Era of Medical Management?

Irving Melita , AlSayed Moeenaldeen , Baujat Genevieve , Ben-Omran Tawfeg , Boero Silvio , Cormier-Daire Valérie , Fauroux Brigitte , Fredwall Svein , Guillen-Navarro Encarna , Kunkel Phillip , Lampe Christian , Leiva-Gea Antonio , Maghnie Mohamad , Mohnike Klaus , Mortier Geert , Pejin Zagorka , Sessa Marco , Sousa Sérgio

Background: Achondroplasia requires lifelong multidisciplinary care. With the advent of targeted medical treatment, The European Achondroplasia Forum (EAF) reviewed existing health surveillance measures in achondroplasia to determine whether they are still relevant.Methods: An online questionnaire was used to assess health status monitoring both in routine clinical practice and in determining response to vosoritide, curr...

hrp0092fc15.4 | Late Breaking Abstracts | ESPE2019

Defects in the GnRH Neuroendocrine Network Affect the Timing of Puberty

Saengkaew Tansit , Mancini Alessandra , Ruiz-Babot Gerard , Cabrera Claudia , Barnes Michael , Dunkel Leo , Guasti Leonardo , Howard Sasha

Background: Self-limited delayed puberty (DP) is an extreme variant of normal pubertal timing and it often clusters in families. Although it is highly heritable and is the most common cause of delayed puberty, little is known about the genetic control. GnRH neuronal biology has been implicated as a key element in the pathogenesis of DP. By focusing on genes involved in GnRH neuron development, migration and function we may understand more about the genetic bas...

hrp0089ha1 | EAP1 mutations cause an impaired transcriptional activity on GnRH promoter that leads to self-limited delayed puberty | ESPE2018

EAP1 Mutations Cause an Impaired Transcriptional Activity on GnRH Promoter that Leads to Self-Limited Delayed Puberty

Mancini Alessandra , Howard Sasha R , Cabrera Claudia P , Barnes Michael R , Heger Sabine , Guasti Leonardo , Ojeda Sergio , Dunkel Leo

Background: The initiation of puberty is orchestrated by the augmentation in the secretion of gonadotropin-releasing hormone (GnRH) from a few thousand neurons located in the hypothalamus. Recent findings identified that the neuroendocrine control of puberty is regulated by a network of transcriptional factors hierarchically organized, but this still remains not fully elucidated. Enhanced At Puberty 1 (EAP1) is one of the main regulators of pubertal onset and it is ex...

hrp0089fc5.5 | Thyroid | ESPE2018

Guidelines for the Management of Paediatric Differentiated Thyroid Carcinoma; a UK Endeavour

Howard Sasha , Newbold Kate , Freeston Sarah , Natu Sonali , Pomplun Sabine , Izatt Louise , Gaze Mark , Barney Harrison , Spoudeas Helen , Wilne Sophie

Objectives: Differentiated thyroid cancer (DTC) has shown increasing incidence in children and young people <19 years (CYP), and CYP present with more extensive disease than in adults and are at risk of long-term morbidity. A paucity of randomised controlled trials in the field has led to a lack of consensus on how these children should best be managed. These Children’s Cancer and Leukaemia Group and British Society for Paediatric Endocrinology and Diabetes commission...

hrp0086fc12.2 | Neuroendocrinology | ESPE2016

LGR4 and EAP1 Mutations are Implicated in the Phenotype of Self-limited Delayed Puberty

Mancini Alessandra , Howard Sasha R , Ruiz-Babot Gerard , Cabrera Claudia P , Barnes Michael R , Guasti Leonardo , Dunkel Leo

Background: Aberrations in the timing of puberty may result in significant adverse health outcomes, including cancers, cardiovascular and neurological pathologies. Self-limited delayed puberty (DP) (i.e. constitutional delay of puberty) runs in families with either autosomal dominant or complex inheritance patterns in >70% of families, indicating a strong genetic basis of the trait. However, only a few genes have been identified underlying DP so far....

hrp0086p2-p773 | Pituitary and Neuroendocrinology P2 | ESPE2016

Primary Thirst Defect is a Rare But Important Complication Following Surgery for Hypothalamic Hamartoma and Intractable Epilepsy

Giri Dinesh , Blair Jo , Das Urmi , Dharmaraj Poonam , Senniappan Senthil , Malluci Connor , Benedetta Pettorini , Pizer Barry , Burns Sasha , Didi Mohammed

Background: Diabetes insipidus (DI) is a well-recognized post neuro surgical complication arising after hypothalamic-pituitary surgery. DI occurring in the post-operative period can be transient happening within 24–48 hour of surgery, secondary to trauma to the connections between the magnocellular bodies and the nerve terminals in the posterior pituitary, or to axonal shock from disturbances in the vascular supply to the pituitary stalk and posterior pituitary.<p cla...

hrp0082p1-d2-216 | Reproduction (1) | ESPE2014

IGSF1 Variants in Boys with Familial Delayed Puberty

Joustra Sjoerd , Wehkalampi Karoliina , Oostdijk Wilma , Biermasz Nienke , Howards Sasha , Bernard Daniel , Maarten Wit Jan , Dunkel Leo , Losekoot Monique

Background: The immunoglobulin superfamily member 1 (IGSF1) gene encodes a plasma membrane glycoprotein enriched in pituitary and testes. Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism (CeH), macroorchidism, and delayed pubertal rise of testosterone despite normal timing of testicular growth. This syndrome was discovered in patients with CeH; therefore, it is presently unknown whether IGSF1 mutations also cau...