Pseudohypoparathyroidism, acrodysostosis, progressive osseous heteroplasia: different names for the same spectrum of diseases?

Pseudohypoparathyroidism (PHP), the first known post-receptorial hormone resistance, derives from a partial deficiency of the alpha subunit of the stimulatory G protein (Gs alpha), a key component of the PTH/PTHrP signaling pathway. Since its first description, different studies unveiled, beside the molecular basis for PHP, the existence of different subtypes and of diseases in differential diagnosis associated with genetic alterations in other genes of the PTH/PTHrP pathway. The clinical and molecular overlap among PHP subtypes and with different but related disorders make both differential diagnosis and genetic counseling challenging. Recently, a proposal to group all these conditions under the novel term inactivating PTH/PTHrP signaling disorders (iPPSD) was promoted and, soon afterwards, the first international consensus statement on the diagnosis and management of these disorders has been published. This review will focus on the major and minor features characterizing PHP/iPPSDs as a group and on the specificities as well as the overlap associated with the most frequent subtypes.

Automated summary

Pseudohypoparathyroidism is a post-receptorial hormone resistance disorder caused by a partial deficiency of the alpha subunit of the stimulatory G protein. In addition to revealing the molecular basis of PHP, different subtypes and diseases associated with genetic alterations in other genes of the PTH/PTHrP pathway have been identified. The clinical and molecular overlap among different diseases makes both differential diagnosis and genetic counseling challenging.