hrp0092p2-48 | Bone, Growth Plate and Mineral Metabolism | ESPE2019

Novel Mutation of the Prkar1a Gene in a Girl with Clinical Diagnosis of Pseudohypoparathyroidism

Toromanovic Alma , Francesca Marta Elli , Mantovani Giovanna

Introduction: Despite the high detection rate of GNAS molecular defects, about 30% of patients with a clinical suspect of PHP/AHO still lack a confirming molecular diagnosis. Mutations in genes encoding proteins crucial for cAMP-mediated signaling have been recently detected in a small subset of patients negative for GNAS defects, showing a phenotypic overlap between PHP and Acrodysostosis.Clinical case pres...

hrp0084p2-210 | Bone | ESPE2015

Genetic and Epigenetic Alterations at the GNAS Locus and Clinical Consequences in Pseudohypoparathyroidism: A New Healthcare Pathway

Giachero Federica , Elli Francesca M , Baricco Marta , Matarazzo Patrizia , Mantovani Giovanna , de Sanctis Luisa

Background: Genetic and epigenetic alterations at the GNAS locus are responsible for the Gsα protein dysfunctions causing Pseudohypoparathyroidism (PHP), a heterogeneous disease characterized by multiple hormone resistances and AHO signs (short stature, obesity, round face, brachydactyly, subcutaneous ossifications and mental retardation). A clinical overlap among molecular subtypes of the disease (Ia, Ib, Ic and II) makes the current classification inadequate; furthermor...

hrp0094fc3.1 | Growth Disorders | ESPE2021

iPPSD: focus on neonatal features, preliminary data from a retrospective analysis of a large cohort of patients.

Del Sindaco Giulia , Pagnano Angela , Berkenou Jugurtha , Rothenbuhler Anya , Arosio Maura , Mantovani Giovanna , Linglart Agnes ,

Since the first description of pseudohypoparathyroidism (PHP), a remarkable clinical variability, which translates in several PHP subtypes, was observed. In 2016 a new classification of this group of diseases have been published by the European Network on PHP and related disorders, proposing “inactivating PTH/PTHrP signaling disorder” (iPPSD) as a new term that encompasses all the clinical entities, stressing the common mechanism responsible for all diseases. iPPSDs ...

hrp0086rfc2.8 | Bone & Mineral Metabolism | ESPE2016

Final Heights and BMI in Patients Affected with Different Types of Pseudohypoparathyroidism

Hanna Patrick , Mantovani Giovanna , Grybek Virginie , Juppner Harald , Brehin Anne-Claire , Kottler Marie-Laure , Rothenbuhler Anya , Linglart Agnes

Background: Pseudohypoparathyroidism type 1A (PHP1A) and PseudoPHP are caused respectively by maternal and paternal mutations involving those GNAS exons that encode the alpha-subunit of the stimulatory G protein (Gsα). Common to different forms of PHP1B is a loss-of-methylation (LOM) at one or several maternal GNAS exons, which likely reduces Gsα expression in certain tissues. In most autosomal dominant PHP1B variants (AD-PHP1B), LOM is restricted t...

hrp0082p2-d1-292 | Bone | ESPE2014

Pseudohypoparathyroidism Type Ib: Two Cases with Different Clinical Presentation

Balsamo Claudia , Baronio Federico , Marsigli Angelica , Bonifacci Valentina , Mantovani Giovanna , Molinaro Angelo , Juppner Harald , Visconti Paola , Mazzanti Laura , Balsamo Antonio

Background: Sporadic pseudohypoparathyroidism type Ib (spor-PHP-Ib) is caused by GNAS methylation alterations with loss of imprinting at the exon A/B differentially methylated region (DMR), without genetic deletions disrupting the STX16 ICR. These patients classically display hormone resistance limited to PTH and TSH with no Albright hereditary osteodistrophy (AHO).Objective and hypotheses: We describe two cases with the same imprinting methylat...

hrp0097p1-517 | Growth and Syndromes | ESPE2023

Bridging the gap between short stature and metabolic alterations in children born small for gestational age: an exploratory study

Rodari Giulia , Citterio Valeria , Collini Valentina , Risio Alessandro , Profka Eriselda , Giacchetti Federico , Arosio Maura , Mantovani Giovanna , Giavoli Claudia

Introduction: Children born small for gestational age (SGA) represent a heterogeneous population, displaying different phenotypes for both growth and metabolic status. Low birth length and/or weight increases the risks for not only growth impairment but also for metabolic derangements (cardiovascular disease, hypertension and type 2 diabetes), the latter with an even amplified risk in children with rapid postnatal weight gain. Variability in metabolic paramete...

hrp0095fc2.6 | Bone, Growth Plate and Mineral Metabolism | ESPE2022

Pseudohypoparathyroidism Type 1A (PHP1A): Growth patterns under growth hormone therapy for short stature

Ertl Diana-Alexandra , Mantovani Giovanna , Perez de Nanclares Guiomar , Gleiss Andreas , Hanna Patrick , Marta Elli Francesca , Pereda Arrate , Rothenbuhler Anya , Audrain Christelle , Berkenou Jugurtha , Linglart Agnes

Background: Pseudohypoparathyroidism 1A, newly classified as inactivating PTH/PTHrP signaling disorder type 2 (iPPSD2), is defined by resistance to parathyroid hormone, short stature and early-onset obesity. Short stature is caused by skeletal dysplasia and additionally, in some cases, also by the coexistence of growth hormone deficiency, as other hormonal resistances might be present (e.g. thyroid-stimulating hormone, growth hormone releasing hormone (GHRH), ...

hrp0092fc6.6 | Bone, Growth Plate and Mineral Metabolism Session 2 | ESPE2019

Craniosynostosis in Inactivating PTH/PTHrP Signaling Disorder 2: A Non-Classical Feature to Consider

Riaño-Galan Isolina , Rothenbuhler Anya , Debza Yahya , Barosi Anna , Mantovani Giovanna , Perez de Nanclares Guiomar , Linglart Agnès

Classic features of inactivating PTH/PTHrP Signaling Disorder 2 or 3 (iPPSD2, iPPSD3), i.e. former pseudohypoparathyroidism include multi-hormone resistance, short stature, subcutaneous ossifications, brachydactyly, and early-onset obesity and a molecular defect at the GNAS region. In addition, patients may present with less-known features including craniosynostosis (CSO).Objective: To describe the prevalence of CSO in a cohort ...

hrp0097rfc2.4 | Bone, Growth Plate and Mineral Metabolism | ESPE2023

Documentation of inactivating PTH/PTHrP Signaling Disorders (Pseudohypoparathyroidism) cases in EuRRECa / EuRR-Bone: a challenging, but worthwhile journey

Ertl Diana-Alexandra , Mantovani Giovanna , Perez de Nanclares Guiomar , Cherenko Mariya , M. de Rooij Tess , L Priego Zurita Ana , M Appelman- Dijkstra Natasha , S Ahmed Faisal , Bryce Jillian , Linglart Agnès

Background: A new classification of pseudohypoparathyroidism is available (Thiele et al. 2016, J Endocrinol). The phenotype variability of inactivating PTH/PTHrP Signaling Disorders (iPPSD, former pseudohypoparathyroidism) cases is still very challenging, even for experts. Thus, it is crucial to collect data in a centralized manner for future investigation.Methods: The EuRRECa/EuRR-Bone registries are the first ...

hrp0086fc2.2 | Bone & Mineral Metabolism | ESPE2016

From Pseudohypoparathyroidism to Inactivating PTH/PTHrP Signaling Disorder (iPPSD), a Novel Classification Proposed by the European EuroPHP-Network

Thiele Susanne , Mantovani Giovanna , Barlier Anne , Bordogna Paola , Elli Francesca M , Freson Kathleen , Garin Intza , Grybek Virginie , Hanna Patrick , Izzi Benedetta , Hiort Olaf , Lecumberri Beatriz , Pereda Arrate , de Sanctis Luisa , Silve Caroline , Turan Serap , Usardi Alessia , Saraff Vrinda , de Nanclares Guiomar Perez , Linglart Agnes

Background: Disorders related to an impairment in parathyroid hormone (PTH) signaling pathway are historically classified under the term pseudohypoparathyroidism (PHP), that now encompasses rare, related but highly heterogeneous diseases with demonstrated (epi)genetic causes. The actual classification is based on the presence or absence of specific clinical and biochemical signs together with an in vivo response to exogenous PTH and an in vitro assay of Gs&#9...