TY - JOUR
T1 - Inactivating PTH/PTHrP signaling disorders (iPPSDs)
T2 - Evaluation of the new classification in a multicenter large series of 544 molecularly characterized patients
AU - Pereda, Arrate
AU - Elli, Francesca M.
AU - Thiele, Suzanne
AU - de Sanctis, Luisa
AU - Rothenbuhler, Anya
AU - Hanna, Patrick
AU - Francou, Bruno
AU - Ertl, Diana Alexandra
AU - de Nanclares, Guiomar Perez
AU - Linglart, Agnès
AU - Mantovani, Giovanna
N1 - Funding Information:
This work was supported by the grant ‘Platforms 2018’ to G M from Fondazione 阀RCCS Ca’ Granda Policlinico Ospedale Maggiore, by grant PR 阀N 2017HBHA98 from M 阀UR-阀talian Ministry of University and Research to G M, AP-HP recurrent funds from the rare disease plan, a grant from the French Society of Pediatric Endocrinology and Diabetology (SFEDP) (to P H), a grant from the 阀nstituto de Salud Carlos 阃阃阀 ( 阀nstitute of Health Carlos of the Ministry of Economy and Competitiveness (Spain) (to G P d N and A P), co-financed by the European Regional Development Fund (P 阀16/00073), a grant from the Department of Health of the Basque Government (GV2017/111040 to G P d N), a 2019 fellowship grant from ESPE (to A E), and the 2019 research unit grant from ESPE (to G d PN, G M, S T, A E, B F and A L).
Publisher Copyright:
© 2021 BioScientifica Ltd.. All rights reserved.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Objective: Pseudohypoparathyroidism and related disorders belong to a group of heterogeneous rare diseases that share an impaired signaling downstream of Gsα-protein-coupled receptors. Affected patients may present with various combination of symptoms including resistance to PTH and/or to other hormones, ectopic ossifications, brachydactyly type E, early onset obesity, short stature and cognitive difficulties. Several years ago we proposed a novel nomenclature under the term of inactivating PTH/PTHrP signaling disorders (iPPSD). It is now of utmost importance to validate these criteria and/or improve the basis of this new classification. Design: Retrospective study of a large international series of 459 probands and 85 relatives molecularly characterized. Methods: Information on major and minor criteria associated with iPPSD and genetic results were retrieved from patient files. We compared the presence of each criteria according to the iPPSD subtype, age and gender of the patients. Results: More than 98% of the probands met the proposed criteria for iPPSD classification. Noteworthy, most patients (85%) presented a combination of symptoms rather than a single sign suggestive of iPPSD and the overlap among the different genetic forms of iPPSD was confirmed. The clinical and molecular characterization of relatives identified familial history as an additional important criterion predictive of the disease. Conclusions: The phenotypic analysis of this large cohort confirmed the utility of the major and minor criteria and their combination to diagnose iPPSD. This report shows the importance of having simple and easily recognizable signs to diagnose with confidence these rare disorders and supports a better management of patients.
AB - Objective: Pseudohypoparathyroidism and related disorders belong to a group of heterogeneous rare diseases that share an impaired signaling downstream of Gsα-protein-coupled receptors. Affected patients may present with various combination of symptoms including resistance to PTH and/or to other hormones, ectopic ossifications, brachydactyly type E, early onset obesity, short stature and cognitive difficulties. Several years ago we proposed a novel nomenclature under the term of inactivating PTH/PTHrP signaling disorders (iPPSD). It is now of utmost importance to validate these criteria and/or improve the basis of this new classification. Design: Retrospective study of a large international series of 459 probands and 85 relatives molecularly characterized. Methods: Information on major and minor criteria associated with iPPSD and genetic results were retrieved from patient files. We compared the presence of each criteria according to the iPPSD subtype, age and gender of the patients. Results: More than 98% of the probands met the proposed criteria for iPPSD classification. Noteworthy, most patients (85%) presented a combination of symptoms rather than a single sign suggestive of iPPSD and the overlap among the different genetic forms of iPPSD was confirmed. The clinical and molecular characterization of relatives identified familial history as an additional important criterion predictive of the disease. Conclusions: The phenotypic analysis of this large cohort confirmed the utility of the major and minor criteria and their combination to diagnose iPPSD. This report shows the importance of having simple and easily recognizable signs to diagnose with confidence these rare disorders and supports a better management of patients.
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U2 - 10.1530/EJE-20-0625
DO - 10.1530/EJE-20-0625
M3 - Article
C2 - 33270042
AN - SCOPUS:85099760814
VL - 184
SP - 311
EP - 320
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 2
ER -