title: From pseudohypoparathyroidism to inactivating PTH/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network.
abstract: OBJECTIVE
  Disorders caused by impairments in the parathyroid hormone (PTH) signalling pathway are historically classified under the term pseudohypoparathyroidism (PHP), which encompasses rare, related and 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 the results of an in vitro assay to measure Gsa protein activity. However, this classification disregards other related diseases such as acrodysostosis (ACRDYS) or progressive osseous heteroplasia (POH), as well as recent findings of clinical and genetic/epigenetic background of the different subtypes. Therefore, the EuroPHP network decided to develop a new classification that encompasses all disorders with impairments in PTH and/or PTHrP cAMP-mediated pathway.
  
  
  METHODS
  Extensive review of the literature was performed. Several meetings were organised to discuss about a new, more effective and accurate way to describe disorders caused by abnormalities of the PTH/PTHrP signalling pathway.
  
  
  CONCLUSIONS
  After determining the major and minor criteria to be considered for the diagnosis of these disorders, we proposed to group them under the term 'inactivating PTH/PTHrP signalling disorder' (iPPSD). This terminology: (i) defines the common mechanism responsible for all diseases; (ii) does not require a confirmed genetic defect; (iii) avoids ambiguous terms like 'pseudo' and (iv) eliminates the clinical or molecular overlap between diseases. We believe that the use of this nomenclature and classification will facilitate the development of rationale and comprehensive international guidelines for the diagnosis and treatment of iPPSDs.
authors.affiliation: Division of Experimental Pediatric Endocrinology and DiabetesDepartment of Pediatrics, University of Lübeck, Lübeck, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Thiele
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoEndocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mantovani
authors.affiliation: APHMHôpital la Conception, Laboratory of Molecular Biology, Marseille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Barlier
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoEndocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Boldrin
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoEndocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bordogna
authors.affiliation: Department of Public Health and Pediatric SciencesUniversity of Torino, Torino, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: De Sanctis
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoEndocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Elli
authors.affiliation: Department of Cardiovascular SciencesCenter for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Freson
authors.affiliation: Molecular (Epi)Genetics LaboratoryBioAraba National Health Institute, OSI Araba University Hospital, Vitoria-Gasteiz, Spain.
authors.forename: Intza
authors.initials: I
authors.lastname: Garin
authors.affiliation: APHPReference Center for rare disorders of the Calcium and Phosphate Metabolism, filière OSCAR and Plateforme d'Expertise Maladies Rares Paris-Sud, Hôpital Bicêtre Paris Sud, Le Kremlin Bicêtre, France.|INSERM U1169Hôpital Bicêtre, Le Kremlin Bicêtre, et Université Paris-Saclay, Le Kremlin Bicêtre, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Grybek
authors.affiliation: APHPReference Center for rare disorders of the Calcium and Phosphate Metabolism, filière OSCAR and Plateforme d'Expertise Maladies Rares Paris-Sud, Hôpital Bicêtre Paris Sud, Le Kremlin Bicêtre, France.|INSERM U1169Hôpital Bicêtre, Le Kremlin Bicêtre, et Université Paris-Saclay, Le Kremlin Bicêtre, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hanna
authors.affiliation: Department of Cardiovascular SciencesCenter for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Izzi
authors.affiliation: Division of Experimental Pediatric Endocrinology and DiabetesDepartment of Pediatrics, University of Lübeck, Lübeck, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Hiort
authors.affiliation: Department of Endocrinology and NutritionLa Paz University Hospital, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lecumberri
authors.affiliation: Molecular (Epi)Genetics LaboratoryBioAraba National Health Institute, OSI Araba University Hospital, Vitoria-Gasteiz, Spain.|Department of Biochemistry and Molecular BiologyUniversity of Basque Country, Leioa, Spain.
authors.forename: Arrate
authors.initials: A
authors.lastname: Pereda
authors.affiliation: Department of Endocrinology and DiabetesBirmingham Children's Hospital, Birmingham, UK.
authors.forename: Vrinda
authors.initials: V
authors.lastname: Saraff
authors.affiliation: APHPReference Center for rare disorders of the Calcium and Phosphate Metabolism, filière OSCAR and Plateforme d'Expertise Maladies Rares Paris-Sud, Hôpital Bicêtre Paris Sud, Le Kremlin Bicêtre, France.|INSERM U1169Hôpital Bicêtre, Le Kremlin Bicêtre, et Université Paris-Saclay, Le Kremlin Bicêtre, France.|APHPService de Biochimie et Génétique Moléculaires, Hôpital Cochin, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Silve
authors.affiliation: Department of PediatricsDivision of Endocrinology and Diabetes, Marmara University, Istanbul, Turkey.
authors.forename: Serap
authors.initials: S
authors.lastname: Turan
authors.affiliation: APHPReference Center for rare disorders of the Calcium and Phosphate Metabolism, filière OSCAR and Plateforme d'Expertise Maladies Rares Paris-Sud, Hôpital Bicêtre Paris Sud, Le Kremlin Bicêtre, France.|APHPDepartment of Paediatric Endocrinology and Diabetology, Bicêtre Paris Sud hospital, Le Kremlin Bicêtre, France.
authors.forename: Alessia
authors.initials: A
authors.lastname: Usardi
authors.affiliation: Division of Experimental Pediatric Endocrinology and DiabetesDepartment of Pediatrics, University of Lübeck, Lübeck, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Werner
authors.affiliation: Molecular (Epi)Genetics LaboratoryBioAraba National Health Institute, OSI Araba University Hospital, Vitoria-Gasteiz, Spain.
authors.forename: Guiomar Perez
authors.initials: GP
authors.lastname: de Nanclares
authors.affiliation: APHPReference Center for rare disorders of the Calcium and Phosphate Metabolism, filière OSCAR and Plateforme d'Expertise Maladies Rares Paris-Sud, Hôpital Bicêtre Paris Sud, Le Kremlin Bicêtre, France agnes.linglart@aphp.fr.|INSERM U1169Hôpital Bicêtre, Le Kremlin Bicêtre, et Université Paris-Saclay, Le Kremlin Bicêtre, France.|APHPDepartment of Paediatric Endocrinology and Diabetology, Bicêtre Paris Sud hospital, Le Kremlin Bicêtre, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Linglart
mesh_terms: D001851:Bone Diseases, Metabolic / Q000097:blood / Q000145:classification / Q000175:diagnosis; D004413:Dysostoses / Q000097:blood / Q000145:classification / Q000175:diagnosis; D005060:Europe; D006801:Humans; D008607:Intellectual Disability / Q000097:blood / Q000145:classification / Q000175:diagnosis; D009999:Ossification, Heterotopic / Q000097:blood / Q000145:classification / Q000175:diagnosis; D010009:Osteochondrodysplasias / Q000097:blood / Q000145:classification / Q000175:diagnosis; D010281:Parathyroid Hormone / Q000097:blood; D044162:Parathyroid Hormone-Related Protein / Q000097:blood; D011547:Pseudohypoparathyroidism / Q000097:blood / Q000145:classification* / Q000175:diagnosis*; D012873:Skin Diseases, Genetic / Q000097:blood / Q000145:classification / Q000175:diagnosis
chemical_list: D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein