hrp0094s10.2 | Pathways to Improved Diagnosis and Management of Hypothalamo-Pituitary Disorders | ESPE2021

Delayed puberty: A genetic condition?

Howard Sasha ,

Young people presenting with delay in pubertal onset or progression may have one of a spectrum of conditions, with different underlying pathological mechanisms. Whilst environmental factors such as nutrition and emotional well-being can influence the timing of puberty, in the majority of patients presenting with significantly delayed puberty there is a clear family history of delayed or arrested puberty. Pubertal timing is known to be a trait with strong heritability, demonstr...

hrp0095wg5.3 | ESPE Working Group on Paediatric and Adolescent Gynaecology (PAG) Symposium | ESPE2022

Differential diagnosis of pubertal delay in girls - What’s new?

Howard Sasha

Pubertal delay in females is defined as the lack of development of Tanner breast stage 2 by 13 years of age. Recent cohort studies have recapitulated the findings of classic studies over the last few decades, that constitutional delay (also known as self-limited delayed puberty) is less common in girls than in boys. This diagnosis is found in 30% of girls presenting with delayed puberty, with a further 30% classified as functional hypogonadotropic hypogonadism due to chronic i...

hrp0089fc13.3 | Pituitary, Neuroendocrinology and Puberty 2 | ESPE2018

Role of GnRH Neuronal Migration and Development in Self-Limited Delayed Puberty

Howard Sasha , Oleari Roberto , Mancini Alessandra , Poliandri Ariel , Saengkaew Tansit , Guasti Leo , Cariboni Anna , Dunkel Leo

Objectives: Several different pathogenic mechanisms may converge on a final common pathway to produce the phenotype of delayed pubertal timing. In our cohort of patients with familial self-limited delayed puberty (DP) we have demonstrated mutations in IGSF10 leading to mis-regulation of the embryonic migration of GnRH neurons (Howard et al, EMBO MM 2016). We aimed to discover novel genetic mutations in pathways regulating GnRH neuronal migration and developme...

hrp0084fc14.2 | Puberty | ESPE2015

A Mutation in HS6ST1 Causes Self-limited Delayed Puberty

Howard Sasha , Poliandri Ariel , Cabrera Claudia , Barnes Michael , Wehkalampi Karoliina , Dunkel Leo

Background: Self-limited delayed puberty (DP) often segregates in an autosomal dominant pattern, suggesting that inheritance is conferred by a small number of genes. However, the underlying genetic background is mostly unknown. By comparison, many genes have been identified where loss-of-function mutations lead to hypogonadotropic hypogonadism (HH). Despite likely overlap between the pathophysiology of delayed puberty and conditions of GnRH deficiency, few studies have examine...

hrp0094fc8.1 | Neuroendocrinology | ESPE2021

Combined omic analysis revealed autism-linked NLGN3 as new candidate gene associated to GnRH neuron development and disease.

Oleari Roberto , Lettieri Antonella , Paganoni Alyssa , Howard Sasha R , Cariboni Anna ,

During development, gonadotropin releasing hormone (GnRH) neurons are born in the nasal placode and migrate to the hypothalamus, where they position to regulate sexual reproduction by pulsatile release of GnRH. Defective GnRH neuron development or action may lead to GnRH deficiency (GD) which is characterized by absent or delayed puberty. Several GD causative genes have been identified so far, but half of the cases are still idiopathic. The employment of complementary research...

hrp0095p1-176 | Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology | ESPE2022

Diagnostic and management practices of girls presenting with polycystic ovary syndrome (PCOS)-like symptoms to a tertiary paediatric endocrine clinic.

Solanas Martín Blanca , R. Howard Sasha , R. Hughes Claire , L. Storr Helen , H. Willemsen Ruben

Background: Polycystic ovary syndrome (PCOS) continues to be a diagnostic challenge in adolescent girls. Symptoms like oligomenorrhea and acne, and polycystic ovarian morphology on ultrasound can be normal variants in adolescents. In addition to diagnostic difficulties, there is lack of randomized controlled trials for PCOS treatments specific to adolescents. Current guidelines for diagnosis and management of PCOS in adolescents have large variations and rely ...

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 ChildrenÂ’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....