title: Acrodysostosis syndromes.
abstract: Acrodysostosis (ADO) refers to a heterogeneous group of rare skeletal dysplasia that share characteristic features including severe brachydactyly, facial dysostosis and nasal hypoplasia. The literature describing acrodysostosis cases has been confusing because some reported patients may have had other phenotypically related diseases presenting with Albright Hereditary Osteodystrophy (AHO) such as pseudohypoparathyroidism type 1a (PHP1a) or pseudopseudohypoparathyroidism (PPHP). A question has been whether patients display or not abnormal mineral metabolism associated with resistance to PTH and/or resistance to other hormones that bind G-protein coupled receptors (GPCR) linked to Gsα, as observed in PHP1a. The recent identification in patients affected with acrodysostosis of defects in two genes, PRKAR1A and PDE4D, both important players in the GPCR-Gsα-cAMP-PKA signaling, has helped clarify some issues regarding the heterogeneity of acrodysostosis, in particular the presence of hormonal resistance. Two different genetic and phenotypic syndromes are now identified, both with a similar bone dysplasia: ADOHR, due to PRKAR1A defects, and ADOP4 (our denomination), due to PDE4D defects. The existence of GPCR-hormone resistance is typical of the ADOHR syndrome. We review here the PRKAR1A and PDE4D gene defects and phenotypes identified in acrodysostosis syndromes, and discuss them in view of phenotypically related diseases caused by defects in the same signaling pathway.
authors.affiliation: INSERM U986, Centre de Référence des Maladies Rares du Métabolisme phospho-calcique, Faculté de Médecine, Université Paris-Sud , Le Kremlin Bicêtre, France ; Laboratoire de Biochimie Hormonale et Génétique, Hôpital Bichat Claude Bernard , Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Silve
authors.affiliation: INSERM U986, Centre de Référence des Maladies Rares du Métabolisme phospho-calcique, Faculté de Médecine, Université Paris-Sud , Le Kremlin Bicêtre, France.
authors.forename: C
authors.initials: C
authors.lastname: Le-Stunff
authors.affiliation: INSERM U986, Centre de Référence des Maladies Rares du Métabolisme phospho-calcique, Faculté de Médecine, Université Paris-Sud , Le Kremlin Bicêtre, France.
authors.forename: E
authors.initials: E
authors.lastname: Motte
authors.affiliation: INSERM U986, Centre de Référence des Maladies Rares du Métabolisme phospho-calcique, Faculté de Médecine, Université Paris-Sud , Le Kremlin Bicêtre, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Gunes
authors.affiliation: INSERM U986, Centre de Référence des Maladies Rares du Métabolisme phospho-calcique, Faculté de Médecine, Université Paris-Sud , Le Kremlin Bicêtre, France ; Service d'Endocrinologie Pediatrique, AP-HP Hôpital Bicêtre , Le Kremlin Bicêtre, France.
authors.forename: A
authors.initials: A
authors.lastname: Linglart
authors.affiliation: INSERM Unité 970, Centre de Recherche Cardiovasculaire, Hôpital Européen Georges Pompidou , Paris, France ; Département de Biologie Hormonale et Métabolique, Faculté de Médecine, Université Paris-Descartes, Assistance Publique-Hôpitaux de Paris (AP-HP), Laboratoire d'Oncogénétique, Hôpital Cochin , Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Clauser