Justicia Grande, AntonioGómez Rial, JoséRivero Calle, IrenePischedda, SaraCurrás Tuala, María JoséGómez Carballa, AlbertoCebey López, MiriamPardo Seco, Jacobo JoséMéndez Gallart, RobertoFernández Seara, María JoséSalas Ellacuriaga, AntonioMartinón Torres, Federico2021-08-042021-08-042021Justicia-Grande AJ, Gómez-Ríal J, Rivero-Calle I, Pischedda S, Curras-Tuala MJ, Gómez-Carballa A, Cebey-López M, Pardo-Seco J, Méndez-Gallart R, Fernández-Seara MJ, Salas A and Martinón-Torres F (2021) Case Report: Two Monochorionic Twins With a Critically Different Course of Progressive Osseus Heteroplasia. Front. Pediatr. 9:662669. doi: 10.3389/fped.2021.662669http://hdl.handle.net/10347/26687Progressive osseous heteroplasia (POH; OMIM 166350) is a rare autosomal-dominant genetic disorder in which extra-skeletal bone forms within skin and muscle tissue. POH is one of the clinical manifestations of an inactivating mutation in the GNAS gene. GNAS gene alterations are difficult matter to address, as GNAS alleles show genetic imprinting and produce several transcript products, and the same mutation may lead to strikingly different phenotypes. Also, most of the publications concerning POH patients are either clinical depictions of a case (or a case series), descriptions of their genetic background, or a tentative correlation of both clinical and molecular findings. Treatment for POH is rarely addressed, and POH still lacks therapeutic options. We describe a unique case of POH in two monochorionic twins, who presented an almost asymptomatic vs. the severe clinical course, despite sharing the same mutation and genetic background. We also report the results of the therapeutic interventions currently available for heterotopic ossification in the patient with the severe course. This article not only critically supports the assumption that the POH course is strongly influenced by factors beyond genetic background but also remarks the lack of options for patients suffering an orphan disease, even after testing drugs with promising in vitro resultsengCopyright © 2021 Justicia-Grande, Gómez-Ríal, Rivero-Calle, Pischedda, Curras-Tuala, Gómez-Carballa, Cebey-López, Pardo-Seco, Méndez-Gallart, Fernández-Seara, Salas and Martinón-Torres. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Progressive osseous heteroplasiaPOHTreatmentGenetic diseasesMonochorionic twinsjournal article10.3389/fped.2021.662669open access