Justicia-Grande Antonio José, Gómez-Ríal Jose, Rivero-Calle Irene, Pischedda Sara, Curras-Tuala María José, Gómez-Carballa Alberto, Cebey-López Miriam, Pardo-Seco Jacobo, Méndez-Gallart Roberto, Fernández-Seara María José, Salas Antonio, Martinón-Torres Federico
Genetics, Vaccines, Infectious Diseases and Pediatrics Research Group (GENVIP Group), Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
Physical Medicine and Rehabilitation Department, Hospital Clínico Universitario de Santiago de Compostela, A Coruña, Spain.
Front Pediatr. 2021 Jun 23;9:662669. doi: 10.3389/fped.2021.662669. eCollection 2021.
Progressive 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 gene. gene alterations are difficult matter to address, as 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 results.
进行性骨化性纤维发育不良（POH；OMIM 166350）是一种罕见的常染色体显性遗传病，骨骼外的骨组织在皮肤和肌肉组织内形成。POH是该基因突变失活的临床表现之一。该基因的改变很难处理，因为等位基因表现出基因印记并产生多种转录产物，并且相同的突变可能导致显著不同的表型。此外，大多数关于POH患者的出版物要么是病例（或病例系列）的临床描述、其遗传背景的描述，要么是临床和分子发现的初步关联。POH的治疗很少被提及，并且POH仍然缺乏治疗选择。我们描述了一例发生在单绒毛膜双胞胎中的独特POH病例，尽管他们具有相同的突变和遗传背景，但其中一人几乎无症状，而另一人临床病程严重。我们还报告了目前对严重病程患者异位骨化可用的治疗干预结果。本文不仅批判性地支持了POH病程受遗传背景以外因素强烈影响的假设，还指出了即使在测试有前景的药物后，患有罕见病的患者仍然缺乏治疗选择这一情况。
