ESPE Abstracts (2018) 89 RFC11.1

aFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; bEndocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; cImprinting and Cancer group, Cancer Epigenetic and Biology Program (PEBC), Institut d’Investigació Biomedica de Bellvitge (IDIBELL), Barecelona, Spain; dPediatric Endocrinology Unit, Department of Public Health and Pediatric Sciences, University of Torino, Torino, Italy; eDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Lübeck, Lübeck, Germany; fAPHP, Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Platform of Expertise Paris-Sud for Rare Diseases and Filière OSCAR; APHP, Endocrinology and Diabetes for Children, Bicêtre Paris-Sud Hospital, Le Kremlin-Bicêtre, France; gDevelopmental Endocrinology Research Group, School of Medicine, Dentistry and Nursing Studies, University of Glasgow, Glasgow, UK; hIPOHA, Italian Progressive Osseous Heteroplasia Association, Cerignola, Foggia, Italy; iK20, French PHP and Related Disorders Patient Association, Jouars Pontchartrain, France; jAPHP, Department of Medicine for Adolescents, Bicêtre Paris Sud Hospital, Le Kremlin-Bicêtre, France; kInsitute of Human Genetics, Technical University of Aachen, Aachen, Germany; lDepartment of Cardiovascular Sciences, Center for Molecular and Vascular Biology, Gasthuisberg, Leuven, Belgium; mAEPHP, Spanish PHP and Related Disorders Patient Association, Huércal-Overa, Almeriá, Spain; nAlbright Center & Center for Rare Bone Disorders, Division of Pediatric Endocrinology & Diabetes, Connecticut Children’s Medical Center and Department of Pediatrics, University of Connecticut School of Medicine, Framington, Connecticut, USA; oAPHP, Department of Endocrinology, Cochin Hospital, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; pDepartment of Medicine, Division of Endocrinology & Centre for Bone Quality, Leiden University Medical Center, Leiden, Netherlands; qINSERM U1169, Bicêtre Paris Sud, Université Paris Sud Paris Saclay, Le Kremlin-Bicêtre, France; rAPHP, Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Platform of Expertise Paris-Sud for Rare Diseases and Filière OSCAR; APHP, Department of Endocrinology and Reproductive Diseases, Bicêtre Paris Sud Hospital; INSERM U1185, Bicêtre Paris Sud, Université Paris Sud Paris Saclay, Le Kremlin-Bicêtre, France; sUK Acrodysostosis Patients’ Group, London, UK; tDepartment of Genetics, Caen University Hospital, Caen, France; uAPHP, Department of Odontology, Bretonneau Hospital PNVS, Paris; Faculty of Dentistry, Paris Descartes University, Montrouge, France; vDepartment of Endocrinology and Nutrition, La Paz University Hospital, Madrid, Spain; wDepartment of Pediatrics, Division of Endocrinology and Diabetes and Center for Bone Health, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA; xUniversity of Helsinki and Helsinki University Hospital, Children’s Hospital, Helsinki, Finland; yLaboratório de Metabolismo e Endocrinologia do Departamento de Fisiologia e Biofísica do Instituto de Ciências Biomédicas da Universidade de São Paulo (ICB-USP), São Paulo, Brazil; zDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, IIS La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid. CIBERobn, ISCIII, Madrid, Spain; aaDivision of Endocrinology, Chiba Children’s Hospital, Chiba, Japan; abDepartment of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester University NHS Foundation Trust, Manchaster, UK; acMolecular (Epi)Genetics Laboratory, BioAraba National Health Institute, Hospital Universitario Araba-Txagorritxu, Vitoria-Gasteiz, Spain; adDepartment of Medicine, Mayo Clinic, Rochester, New York, USA; aeDepartment of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; afDepartment of Endocrinology and Diabetes, Birmingham Children’s Hospital, Birmingham, UK; agPediatric Endocrinology and Diabetes, Vanderbilt University Medical Center, Nashville, Tennessee, USA; ahDepartments of Orthopaedic Surgery and Genetics, Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; aiAPHP, Service de Biochimie et Génétique Moléculaires, Hôpital Cochin, Paris, France; ajDepartment of Pediatrics, Division of Endocrinology and Diabetes, Marmara University, Istanbul, Turkey; akUK Acrodysostosis Patients’ Group, London, UK; alDepartment of Internal Medicine, Bone Center Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands

Pseudohypoparathyroidism (PHP) and related disorders lead to a wide spectrum of abnormal physical characteristics, neurocognitive and endocrine abnormalities. PHP (including all subtypes), pseudoPHP, acrodysostosis and progressive osseous heteroplasia refer to heterogeneous disorders characterized by physical findings, differently associated in each subtype, including short bones, short stature, stocky build, subcutaneous ectopic ossifications, as well as laboratory abnormalities such as hypocalcemia, hyperphosphatemia, and elevated PTH and TSH levels. Other features have been attributed to these disorders, such as intrauterine growth failure, early-onset obesity, hypogonadism, hypothyroidism, elevated calcitonin levels, growth hormone deficiency and neurocognitive deficiency. The main subtypes of PHP and related disorders are caused by de novo or autosomal dominantly inherited inactivating genetic mutations, and/or epigenetic, sporadic or genetic-based alterations within or upstream of GNAS, PRKAR1A, and PDE4D and PDE3A. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between different types. A specific diagnosis is often delayed due to lack of recognition of the syndrome(s) and associated features. In addition, caregivers and patients are lacking guidelines for the daily life management of patients. Our aim was to provide evidence based recommendations on clinical diagnosis, molecular confirmation of the genetic or the epigenetic defect and management of most frequent manifestations of these rare diseases. Therefore a consensus statement supported by several patients associations and scientific societies was prepared for 2 years. After a comprehensive literature search using PubMed, >800 papers published since January 1st, 1990 to December 18th, 2016 have been reviewed. The approach comprised 2 pre-consensus meetings, an expert consensus meeting, and a Delphi-like methodology, adjusted to rare diseases. Experts agreed that the diagnosis of PHP is based on major criteria including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular analysis. The management of PHP and related disorders requires a multidisciplinary approach including a transition program from pediatric to adult care. Patients should be screened for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight, glucose intolerance or diabetes, hypertension, as well as ectopic ossifications and neurocognitive impairment. Overall, a coordinated approach from infancy through adulthood should help us to improve the care of patients affected by these disorders.

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