Pdf Fibrodysplasia Ossificans Progressiva Diagnosis Management And

Leo Migdal

-Dec 6, 2025, 4:26 AM

pdf fibrodysplasia ossificans progressiva diagnosis management and

Academia.edu no longer supports Internet Explorer. To browse Academia.edu and the wider internet faster and more securely, please take a few seconds to upgrade your browser. 2013, Pediatric endocrinology reviews : PER Fibrodysplasia ossificans progressiva (FOP), a rare and disabling genetic condition characterized by congenital malformations of the great toes and progressive heterotopic endochondral ossification (HEO) which is the most catastrophic of HEO disorders in humans. Flare-ups of FOP are episodic; immobility is cumulative. Heterozygous activating mutations in activin receptor IA/activin-like kinase-2 (ACVRI/ ALK2), a bone morphogenetic protein (BMP) type I receptor, exist in all sporadic and familial cases of FOP.

The discovery of the FOP gene established a critical milestone in our understanding of FOP, and revealed a highly conserved therapeutic target in the BMP signaling pathway. This discovery has advanced efforts to develop novel therapies for this disabling disorder of tissue metamorphosis. While effective treatment of FOP will likely be based on interventions that modulate overactive ACVR1/ALK2 signaling, or that specifically block postnatal HEO, current management is focused on ... Heterotopic ossification (HO) is a disorder characterised by the formation of ectopic bone in soft tissue. Acquired HO typically occurs in response to trauma and is relatively common, yet its aetiology remains poorly understood. Genetic forms, by contrast, are very rare, but provide insights into the mechanisms of HO pathobiology.

Fibrodysplasia ossificans progressiva (FOP) is the most debilitating form of HO. All patients reported to date carry heterozygous gain-of-function mutations in the gene encoding activin A receptor type I (ACVR1). These mutations cause dysregulated bone morphogenetic protein (BMP) signalling, leading to HO at extraskeletal sites including, but not limited to, muscles, ligaments, tendons and fascia. Ever since the identification of the causative gene, developing a cure for FOP has been a focus of investigation, and studies have decoded the pathophysiology at the molecular and cellular levels, and explored novel... Based on the established... Corresponding Author: Frederick S.

Kaplan, M.D. Isaac & Rose Nassau Professor of Orthopaedic Molecular Medicine The University of Pennsylvania School of Medicine Department of Orthopaedic Surgery Silverstein Two Hospital of the University of Pennsylvania 3400 Spruce Street Philadelphia, Pennsylvania 19104... Fibrodysplasia ossificans progressiva (FOP), a rare and disabling genetic condition characterized by congenital malformations of the great toes and progressive heterotopic endochondral ossification (HEO) which is the most catastrophic of HEO disorders in humans. Flare-ups of FOP are episodic; immobility is cumulative. Heterozygous activating mutations in activin receptor IA/activin-like kinase-2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor, exist in all sporadic and familial cases of FOP. The discovery of the FOP gene established a critical milestone in our understanding FOP, and revealed a highly conserved therapeutic target in the BMP signaling pathway.

This discovery has advanced efforts to develop novel therapies for this disabling disorder of tissue metamorphosis. While effective treatment for FOP will likely be based on interventions that modulate overactive ACVR1/ALK2 signaling, or that specifically block postnatal HEO, current management is focused on early diagnosis, assiduous avoidance of injury or... Keywords: fibrodysplasia ossificans progressiva, heterotopic ossification, activin receptor IA/activin-like kinase-2 (ACVR1/ALK2), BMP signaling Fibrodysplasia ossificans progressiva (FOP) is a rare and disabling disorder with a worldwide prevalence of approximately one in two million individuals. There is no ethnic, racial, gender, or geographic predisposition [1, 2]. Two clinical features define classic FOP: malformations of the great toes and progressive heterotopic endochondral ossification (HEO) in characteristic anatomic patterns.

Individuals with FOP appear normal at birth except for malformations of the great toes that are present in all classically affected individuals. During the first decade of life, most children with FOP develop episodic, painful inflammatory soft tissue swellings (or flare-ups). While some flare-ups regress spontaneously, most transform soft connective tissues including aponeuroses, fascia, ligaments, tendons, and skeletal muscles into mature heterotopic bone. Ribbons, sheets, and plates of heterotopic bone replace skeletal muscles and connective tissues through a process of endochondral ossification that leads to an armament-like encasement of bone and permanent immobility. Minor trauma such as intramuscular immunizations, mandibular blocks for dental work, muscle fatigue, blunt muscle trauma from bumps, bruises, falls, or influenza-like viral illnesses can trigger painful new flare-ups of FOP leading to progressive... Surgical removal of heterotopic bone provokes explosive and painful new bone growth.

Pdf Fibrodysplasia Ossificans Progressiva Diagnosis Management And

People Also Search

Academia.edu No Longer Supports Internet Explorer. To Browse Academia.edu And

The Discovery Of The FOP Gene Established A Critical Milestone

Fibrodysplasia Ossificans Progressiva (FOP) Is The Most Debilitating Form Of

Kaplan, M.D. Isaac & Rose Nassau Professor Of Orthopaedic Molecular

This Discovery Has Advanced Efforts To Develop Novel Therapies For