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.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology