scholarly journals Pregnancy in fibrodysplasia ossificans progressiva

2011 ◽  
Vol 5 (1) ◽  
pp. 35-38
Author(s):  
Javaid A Muglu ◽  
Aditya Garg ◽  
T Pandiarajan ◽  
Eileen M Shore ◽  
Frederick S Kaplan ◽  
...  
Keyword(s):  
Early Childhood ◽  
Soft Tissue ◽  
Clinical Course ◽  
Genetic Disorder ◽  
Early Adulthood ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Heterotopic Bone ◽  
Reproductive Decisions ◽  
Heterotopic Bone Formation ◽  
Post Traumatic

Fibrodysplasia ossificans progressiva (FOP) is a rare disabling genetic disorder characterized by progressive postnatal heterotopic ossification leading to cumulative disability. Heterotopic bone formation in FOP usually begins in early childhood following a series of painful, post-traumatic, inflammatory soft-tissue swellings known as flare-ups, which later undergo ossification resulting in the progressive immobilization of the chest wall, limbs and jaw by early adulthood. Pregnancy in FOP has occurred infrequently and reproductive decisions are a dilemma for an individual or couple with FOP. We present the clinical course, medical management and potential concerns of four cases of pregnancy in FOP.

scholarly journals The role of Activin A in fibrodysplasia ossificans progressiva: a prominent mediator

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Hui Lin ◽  
Fuli Shi ◽  
Jiayu Gao ◽  
Ping Hua
Keyword(s):  
Signaling Pathway ◽  
Genetic Disorder ◽  
Activin A ◽  
Bmp Signaling ◽  
The Body ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Type I ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation

Abstract Heterotopic ossification (HO) is the aberrant formation of mature, lamellar bone in nonosseous tissue. Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disorder that causes progressive HO in the ligaments, tendons, and muscles throughout the body. FOP is attributed to an autosomal mutation in activin receptor-like kinase 2 (ALK2), a bone morphogenetic protein (BMP) type I receptor. Initial studies show that mutant ALK2 drives HO by constitutively activating the BMP signaling pathway. Recently, mutant ALK2 has been shown to transduce Smad1/5 signaling and enhance chondrogenesis, calcification in response to Activin A, which normally signals through Smad2/3 and inhibits BMP signaling pathway. Furthermore, Activin A induces heterotopic bone formation via mutant ALK2, while inhibition of Activin A blocks spontaneous and trauma-induced HO. In this manuscript, we describe the molecular mechanism of the causative gene ALK2 in FOP, mainly focusing on the prominent role of Activin A in HO. It reveals a potential strategy for prevention and treatment of FOP by inhibition of Activin A. Further studies are needed to explore the cellular and molecular mechanisms of Activin A in FOP in more detail.

scholarly journals Post-traumatic stiff elbow

2018 ◽  
Vol 3 (5) ◽  
pp. 210-216 ◽  
Author(s):  
Lars Adolfsson
Keyword(s):  
Soft Tissue ◽  
Elbow Joint ◽  
Recent Literature ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Stiff Elbow ◽  
Complete Restoration ◽  
Post Traumatic ◽  
Upper Extremity Function ◽  
Treatment Alternatives

Post-traumatic and post-operative stiffness of the elbow joint is relatively common and may in pronounced cases markedly interfere with normal upper extremity function. Soft-tissue contractures and heterotopic bone formation are two major causes of limited movement. Extensive recent research has elucidated many of the pathways contributing to these conditions, but the exact mechanisms are still unknown. In the early phase of soft-tissue contractures conservative treatment may be valuable, but in longstanding cases operative treatment is often necessary. Several different options are available depending on the severity of the condition and the underlying offending structures. Surgical treatment may allow significant gains in movement but rarely complete restoration, and complications are not uncommon. The following presentation reviews the recent literature on pathomechanisms and treatment alternatives. Cite this article: EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170062

The unique activity of bone morphogenetic proteins in bone: a critical role of the Smad signaling pathway

2013 ◽  
Vol 394 (6) ◽  
pp. 703-714 ◽  
Author(s):  
Takenobu Katagiri ◽  
Sho Tsukamoto
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Type I ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Abstract Bone morphogenetic proteins (BMPs) are multifunctional cytokines that belong to the transforming growth factor-β family. BMPs were originally identified based on their unique activity, inducing heterotopic bone formation in skeletal muscle. This unique BMP activity is transduced by specific type I and type II transmembrane kinase receptors. Among the downstream pathways activated by these receptors, the Smad1/5/8 transcription factors appear to play critical roles in BMP activity. Smad1/5/8 transcription factors are phosphorylated at the C-terminal SVS motif by BMP type I receptors and then induce the transcription of early BMP-responsive genes by binding to conserved sequences in their enhancer regions. The linker regions of Smad1/5/8 contain multiple kinase phosphorylation sites, and phosphorylation and dephosphorylation of these sites regulate the transcriptional activity of Smad proteins. Gain-of-function mutations in one BMP type I receptor have been identified in patients with fibrodysplasia ossificans progressiva, a rare genetic disorder that is characterized by progressive heterotopic bone formation in the skeletal muscle. The mutant receptors activate the Smad signaling pathway even in the absence of BMPs, therefore novel inhibitors for the BMP receptor – Smad axis are being developed to prevent heterotopic bone formation in fibrodysplasia ossificans progressiva. Taken together, the data in the literature show that the BMP type I receptor – Smad signaling axis is the critical pathway for the unique activity of BMPs and is a potential therapeutic target for pathological conditions caused by inappropriate BMP activity.

Colon adenocarcinoma metastasis to soft tissue of the wrist with heterotopic bone formation: a case study

Grand Rounds ◽  
2014 ◽  
Vol 14 (1) ◽  
pp. 16-20
Author(s):  
Elizabeth Killiam ◽  
Robert Cicchino ◽  
Troy Foster ◽  
Jeffrey Stead
Keyword(s):  
Soft Tissue ◽  
Bone Formation ◽  
Colon Adenocarcinoma ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation

scholarly journals Post-COVID-19 exacerbation of fibrodysplasia ossificans progressiva with multiple flare-ups and extensive heterotopic ossification in a 45-year-old female patient

2021 ◽  
Author(s):  
Lovorka Grgurevic ◽  
Rudjer Novak ◽  
Stela Hrkac ◽  
Grgur Salai ◽  
Simeon Grazio
Keyword(s):  
Heterotopic Ossification ◽  
Female Patient ◽  
Soft Tissues ◽  
Hereditary Disease ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Cytokine Analysis ◽  
Viral Illness ◽  
First Time

AbstractFibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable course characterized by occasional flare-ups of heterotopic ossification (HO) in soft tissues that are followed by swelling, stiffness, pain and warmth. Here, we report for the first time a case of a 45-year-old female patient with known FOP recovering from COVID-19 with disease progression potentially linked with the viral illness. In December 2020 the patient contracted a mild form of COVID-19 infection without need for hospital admission. Since January 2021, the patient felt unwell, with occasional abdominal pain which progressively intensified. In March 2021 she presented with new onset of HO, complaining of pain, swelling and thickening sensation in the lower abdomen and left part of the neck. Computerized tomography (CT) and cytokine analysis were performed. CT scan revealed new heterotopic bone formation in multiple soft tissue areas of the neck indicating clear radiological progression. Radiotherapy, which has proven to be an efficient tool to control HO in this patient, was not able to halt HO formation after COVID-19 infection. Cytokine analysis of a plasma sample obtained during a flare-up after COVID-19 infection showed a significantly elevated pro-inflammatory cytokines compared to a flare-up panel prior to infection. Of the 23 analyzed levels of cytokines, a staggering number of 21 were above normal levels. This case is the first confirmation of uncontrolled post-COVID-19 effects in a FOP patient, which manifested with flare-ups followed by progressive HO, possibly caused by a thus far, never described form of post-COVID syndrome.

scholarly journals A RARE VARIANT OF THE HEREDITARY FORM OF MYOSITIS OSSIFICANS IN CLINICAL PRACTICE OF ONCOLOGIST

2020 ◽  
Vol 66 (3) ◽  
pp. 302-307
Author(s):  
Tatyana Kazubskaya ◽  
V. Kozlova ◽  
Yevgeniy Trofimov ◽  
Svetlana Mikhaylova ◽  
Olga Shchagina ◽  
...  
Keyword(s):  
Multidisciplinary Approach ◽  
Soft Tissues ◽  
Myositis Ossificans ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Initial Manifestation ◽  
Femur Neck ◽  
Morphological Picture ◽  
Previous Trauma

Myositis ossificans is a rare disorder, characterized by heterotopic bone formation in muscles or soft tissues which is often mistaken for neoplasia. The reasons for ossification in these tissues may be different. In most cases there is a previous trauma, but etiology may be inheritable. Heritable myositis ossificans also called Fibrodysplasia Ossificans Progressiva (FOP) is associated with mutations in the ACVR1 gene and congenital abnormalities, of which malformations of the great toes is constant as well as wide femur neck. We report a case of FOP in the 9-year-old girl admitted to the clinic with swelling of the scapula and neck with a supposed diagnosis of mesenchymoma. The identified a rare germline mutation in the ACVR1 gene was the decisive factor in confirming the diagnosis of the initial manifestation of FOP, before features of ossification can be were visible during histological examination. The case is of interest because of the rarity of the pathology and the difficulty of diagnosing the early manifestation of POF before the formation of the morphological picture and the need for a multidisciplinary approach in the management of these patients

scholarly journals ACVR1R206H FOP mutation alters mechanosensing and tissue stiffness during heterotopic ossification

2019 ◽  
Vol 30 (1) ◽  
pp. 17-29 ◽  
Author(s):  
Julia Haupt ◽  
Alexandra Stanley ◽  
Claire M. McLeod ◽  
Brian D. Cosgrove ◽  
Andria L. Culbert ◽  
...  
Keyword(s):  
Heterotopic Ossification ◽  
Cell Fate ◽  
Genetic Disorder ◽  
Bmp Signaling ◽  
Fibrodysplasia Ossificans Progressiva ◽  
In Vitro Assays ◽  
Type I ◽  
Heterotopic Bone ◽  
Mechanical Stimuli ◽  
Tissue Microenvironment

An activating bone morphogenetic proteins (BMP) type I receptor ACVR1 (ACVR1R206H) mutation enhances BMP pathway signaling and causes the rare genetic disorder of heterotopic (extraskeletal) bone formation fibrodysplasia ossificans progressiva. Heterotopic ossification frequently occurs following injury as cells aberrantly differentiate during tissue repair. Biomechanical signals from the tissue microenvironment and cellular responses to these physical cues, such as stiffness and rigidity, are important determinants of cell differentiation and are modulated by BMP signaling. We used an Acvr1R206H/+ mouse model of injury-induced heterotopic ossification to examine the fibroproliferative tissue preceding heterotopic bone and identified pathologic stiffening at this stage of repair. In response to microenvironment stiffness, in vitro assays showed that Acvr1R206H/+ cells inappropriately sense their environment, responding to soft substrates with a spread morphology similar to wild-type cells on stiff substrates and to cells undergoing osteoblastogenesis. Increased activation of RhoA and its downstream effectors demonstrated increased mechanosignaling. Nuclear localization of the pro-osteoblastic factor RUNX2 on soft and stiff substrates suggests a predisposition to this cell fate. Our data support that increased BMP signaling in Acvr1R206H/+ cells alters the tissue microenvironment and results in misinterpretation of the tissue microenvironment through altered sensitivity to mechanical stimuli that lowers the threshold for commitment to chondro/osteogenic lineages.

scholarly journals Myositis Ossificans – A Case Report

1970 ◽  
Vol 18 (1) ◽  
pp. 79-81
Author(s):  
F Sultana ◽  
MA Quddus ◽  
MM Rahman ◽  
SM Nuruzzaman
Keyword(s):  
Autosomal Dominant ◽  
Myositis Ossificans ◽  
The Body ◽  
Medical College Hospital ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
College Hospital ◽  
Familial Predisposition ◽  
Medical College ◽  
Post Traumatic

Myositis Ossificans is classified into three types: progressive, post traumatic and paraplegic. The progressive form, myositis ossoificans congenita, is a hereditary disease which is usually autosomal dominant or an isolated mutation and more common in boys. Post-traumatic myositis is found following massive trauma and paraplegic myositis occurs below the level of paralysis. Here, a heterotopic bone formation is evident in the muscle or soft tissue, which can occur almost anywhere in the body. An incidental case of myositis ossificans was found in the Department of Radiology & Imaging, Dhaka Medical College Hospital, Dhaka in March, 2009. A male patient of 22 years of age was sent for radiological investigations from the medicine out patient department (MOPD) of Dhaka Medical College Hospital, Dhaka having complaints of backache and pain in the neck and chest. He was diagnosed as a case of myositis ossificans after the radiological report. It was an incidental finding having no history of trauma or familial predisposition. This case is presented for journal record and academic interest. Key words: Myositis Ossificans; autosomal dominant. DOI: 10.3329/jdmc.v18i1.6312 J Dhaka Med Coll. 2008; 18(1) : 79-81

scholarly journals Over-expression of wild-type ACVR1 in fibrodysplasia ossificans progressiva mice rescues perinatal lethality and inhibits heterotopic ossification

2021 ◽  
Author(s):  
Masakazu Yamamoto ◽  
Sean J Stoessel ◽  
Shoko Yamamoto ◽  
David J Goldhamer
Keyword(s):  
Heterotopic Ossification ◽  
Cultured Cells ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Clinical Aspects ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Wild Type ◽  
Over Expression ◽  
Severity Of Injury ◽  
Perinatal Lethality

Fibrodysplasia ossificans progressiva (FOP) is a devastating disease of progressive heterotopic bone formation for which effective treatments are currently unavailable. FOP is caused by dominant gain-of-function mutations in the receptor ACVR1 (also known as ALK2), which render the receptor inappropriately responsive to activin ligands. In previous studies, we developed a genetic mouse model of FOP that recapitulates most clinical aspects of the disease. In this model, genetic loss of the wild-type Acvr1 allele profoundly exacerbated heterotopic ossification, suggesting the hypothesis that the stoichiometry of wild-type and mutant receptors dictates disease severity. Here, we tested this model by producing FOP mice that conditionally over-express human wild-type ACVR1. Injury-induced heterotopic ossification (HO) was completely blocked in FOP mice when expression of both the mutant and wild-type receptor were targeted to Tie2-positive cells, which includes fibro/adipogenic progenitors (FAPs). Perinatal lethality of Acvr1R206H/+ mice was rescued by constitutive ACVR1 over-expression and these mice survived to adulthood at predicted Mendelian frequencies. Constitutive over-expression of ACVR1 also provided protection from spontaneous HO, and the incidence and severity of injury-induced HO in these mice was dramatically reduced. Analysis of pSMAD1/5/8 signaling both in cultured cells and in vivo indicates that ACVR1 over-expression functions cell-autonomously by reducing osteogenic signaling in response to activin A. Manipulating the stoichiometry of FOP-causing and wild-type ACVR1 receptors may provide the foundation for novel therapeutic strategies to treat this devastating disease.

scholarly journals Percutaneous fixation of acetabular fractures

2018 ◽  
Vol 3 (5) ◽  
pp. 326-334 ◽  
Author(s):  
Horacio Caviglia ◽  
Adrian Mejail ◽  
Maria Eulalia Landro ◽  
Nosratolah Vatani
Keyword(s):  
Acetabular Fractures ◽  
Percutaneous Technique ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Percutaneous Approach ◽  
Screw Insertion ◽  
Quadrilateral Plate ◽  
Bone Fragments ◽  
Post Traumatic ◽  
Joint Congruence

The objective of surgery for acetabular fractures is to achieve precise reduction to restore joint congruence, fix internal bone fragments, avoid displacement of the fracture and allow rapid rehabilitation. Open reduction and internal fixation is the benchmark method for displaced acetabular fractures, but open reductions can increase morbidity, causing neurovascular injury, blood loss, heterotopic bone formation, infection and poor wound healing. An anatomical reduction with a gap of 2 mm or less is a predictor of good joint function and reduced risk of post-traumatic osteoarthritis. The percutaneous approach is associated with fewer complications than open techniques, but acetabular geometry makes percutaneous screw insertion a challenging procedure. The percutaneous technique is recommended for non-displaced or slightly displaced fractures, and in obese, osteoporotic and elderly patients who cannot receive total joint arthroplasty. We recommend the use of intramedullary cannulated screws. Fracture reductions are achieved by manual traction of the affected bones. If some fracture displacement remains, accessory windows can be used to introduce a ball spike pusher, a hook or a Steinmann pin which can be used as a joystick to rotate the fracture. In this paper, we describe the accessory windows for the anterior column, the quadrilateral plate and the posterior column. We detail the position, direction and kind of screws used to stabilize the anterior and posterior columns. Cite this article: EFORT Open Rev 2018;3 DOI: 10.1302/2058-5241.3.170054

Sign in / Sign up

Export Citation Format

Share Document