Fibrodysplasia ossificans progressiva: current concepts from bench to bedside CLINICAL PUZZLE

ABSTRACT 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 management strategies. Based on the established role of BMP signalling throughout HO in FOP, therapeutic modalities that target multiple levels of the signalling cascade have been designed, and some drugs have entered clinical trials, holding out hope of a cure. A potential role of other signalling pathways that could influence the dysregulated BMP signalling and present alternative therapeutic targets remains a matter of debate. Here, we review the recent FOP literature, including pathophysiology, clinical aspects, animal models and c...
Source: DMM Disease Models and Mechanisms - Category: Biomedical Science Authors: Tags: Rare diseases CLINICAL PUZZLE Source Type: research

Related Links:

We report a patient with FOP suffering from life-threatening antibiotic resistant bacterial infected ulcers of the right lower leg and foot. The anesthetic, surgical and postoperative challenges and considerations are discussed. In addition, the literature on limb surgeries of FOP patients is systemically reviewed. The 44 year-old female patient was scheduled for a through-knee amputation. Airway and pulmonary evaluation elicited severe abnormalities, rendering standard general anesthesia a rather complication-prone approach in this patient. Thus, regional anesthesia, supplemented with intravenous analgosedation and N2O-in...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Genetic contributors to cardiac arrhythmias are often found in cardiovascular conduction pathways and ion channel proteins. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disease of massive heter...
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Research Source Type: research
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disease characterized by heterotopic ossification (HO) in soft tissues and caused by a mutation of the ACVR1A/ALK2 gene. Activin-A is a key...
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Research Source Type: research
Rationale: Fibrodysplasia ossificans progressiva (FOP) is rare genetic disease featuring progressive heterotopic ossification of soft tissues of the musculoskeletal system which leads to severe disability and premature death. Recognition of this disease is important since invasive diagnostic procedures can promote disease progression. However, despite its distinctive clinical manifestations, diagnosis can be difficult because of its rarity Patient concerns: A 20-year-old woman was referred to rheumatology clinic for management of “ankylosing spondylitis”. The patent had begun to have hard subcutaneous nodu...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
Purpose of review Fibrodysplasia ossificans progressiva (FOP) is an extremely rare and severely disabling autosomal dominant disease that is yet to be clearly understood. The purpose of this review is to present recent literature on pathophysiology, clinical features, diagnosis and treatment of FOP. Recent findings FOP is characterized by congenital great toe deformity and progressive heterotopic ossifications in connective tissue. Heterotopic ossifications occur after painful flare-ups that can arise spontaneously or can be triggered by minor trauma. Each flare-up ultimately causes restriction of related-joint, and a...
Source: Current Opinion in Pediatrics - Category: Pediatrics Tags: GENETICS: Edited by Nathaniel H. Robin Source Type: research
The original version of this article [1] unfortunately included an error to an author ’s name. Author Maja Di Rocco was erroneously presented as Maja DiRocco.
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Correction Source Type: research
Fibrodysplasia Ossificans Progressiva (FOP; OMIM#135100) is an ultra-rare, severely disabling genetic disease characterized by congenital malformation of the great toes and progressive heterotopic ossification...
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Research Source Type: research
AbstractIncreasing knowledge in the field of rare diseases has led to new therapeutic approaches in the last decade. Treatment strategies have been developed after elucidation of the underlying genetic alterations and pathophysiology of certain diseases (e.g., in osteogenesis imperfecta, achondroplasia, hypophosphatemic rickets, hypophosphatasia and fibrodysplasia ossificans progressiva). Most of the drugs developed are specifically designed agents interacting with the disease-specific cascade of enzymes and proteins involved. While some are approved (asfotase alfa, burosumab), others are currently being investigated in ph...
Source: Pediatric Drugs - Category: Pediatrics Source Type: research
Abstract Increasing knowledge in the field of rare diseases has led to new therapeutic approaches in the last decade. Treatment strategies have been developed after elucidation of the underlying genetic alterations and pathophysiology of certain diseases (e.g., in osteogenesis imperfecta, achondroplasia, hypophosphatemic rickets, hypophosphatasia and fibrodysplasia ossificans progressiva). Most of the drugs developed are specifically designed agents interacting with the disease-specific cascade of enzymes and proteins involved. While some are approved (asfotase alfa, burosumab), others are currently being investig...
Source: Paediatric Drugs - Category: Pediatrics Authors: Tags: Paediatr Drugs Source Type: research
Gain-of-function mutations in the Type I Bone Morphogenic Protein (BMP) receptor ACVR1 have been identified in two diseases: Fibrodysplasia Ossificans Progressiva (FOP), a rare autosomal dominant disorder characterized by genetically driven heterotopic ossification, and in 20 –25% of Diffuse Intrinsic Pontine Gliomas (DIPGs), a pediatric brain tumor with no effective therapies and dismal median survival. While the ACVR1 mutation is causal for FOP, its role in DIPG tumor biology remains under active investigation.
Source: Bone - Category: Orthopaedics Authors: Tags: Full Length Article Source Type: research
More News: Biomedical Science | Clinical Trials | Fibrodysplasia Ossificans Progressiva | Genetics | Rare Diseases | Study