Fibrodysplasia Ossificans Progressiva: Turning into Stone!
(Source: Indian Journal of Pediatrics)
Source: Indian Journal of Pediatrics - March 14, 2020 Category: Pediatrics Source Type: research

Serum osteocalcin level is associated with the mortality in Chinese patients with Fibrodysplasia ossificans progressiva aged ≤18 years at diagnosis
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by extraskeletal heterotopic ossification. It is well recognized that FOP can lead to a devastating condition of disa... (Source: BMC Musculoskeletal Disorders)
Source: BMC Musculoskeletal Disorders - March 6, 2020 Category: Orthopaedics Authors: Dunmin She, Ran Li, Ping Fang, Guannan Zong, Ying Xue and Keqin Zhang Tags: Research article Source Type: research

ALK2: A Therapeutic Target for Fibrodysplasia Ossificans Progressiva and Diffuse Intrinsic Pontine Glioma.
Abstract Fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG) are diseases that typically manifest in childhood and are associated with severely reduced life expectancy. However, there are currently no effective therapies for these diseases, which remain incurable. Activin receptor-like kinase-2 (ALK2), encoded by the ACVR1 gene, is a bone morphogenetic protein (BMP) type-I receptor subtype that plays an important physiological role in the development of bones, muscles, brain, and other organs. Constitutively active mutants of ALK2 have been identified as causative of FOP and inv...
Source: Chemical and Pharmaceutical Bulletin - March 4, 2020 Category: Drugs & Pharmacology Authors: Sekimata K, Sato T, Sakai N Tags: Chem Pharm Bull (Tokyo) Source Type: research

Radiotherapy in Fibrodysplasia Ossificans Progressiva: A Case Report and Systematic Review of the Literature
In conclusion, available reports suggest no contraindication to radiotherapy in FOP patients; although the number of cases was small, systematic toxicity reports often were not available, and none of the reports described high-dose, high-energy radiation treatment at locations such as muscle and joint regions. (Source: Frontiers in Endocrinology)
Source: Frontiers in Endocrinology - February 12, 2020 Category: Endocrinology Source Type: research

Successful Airway and Anesthesia Management Using a High-Flow Nasal Cannula in a Fibrodysplasia Ossificans Progressiva Patient During General Anesthesia: A Case Report
Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary disorder causing neck stiffness, ankylosis of temporomandibular joints, and severe restrictive respiratory dysfunction due to progressive heterotopic ossification of the connective tissue. Herein, we report a case of successful airway and anesthesia management using a high-flow nasal cannula (HFNC) in a 51-year-old man with FOP undergoing partial bone resection of the right greater trochanter of the femur. Although general anesthesia with awake fiberoptic nasotracheal intubation has been described as the gold standard, HFNC may yield another potentially viabl...
Source: A&A Case Reports - February 1, 2020 Category: Anesthesiology Tags: Case Reports Source Type: research

Fibrodysplasia ossificans progressiva as a form of pseudodystonia
We describe potential mechanisms that can be responsible for the good outcome of BoNT/A therapy observed in our patient. (Source: Parkinsonism and Related Disorders)
Source: Parkinsonism and Related Disorders - January 31, 2020 Category: Neurology Authors: Jaros ław Dulski Tags: Correspondence Source Type: research

Reply to J. Dulski and J. Slawek's “Fibrodysplasia ossificans progressiva as a form of pseudodystonia”
We thank Dr Dulski and Dr Slawek for sharing their fascinating case of pseudodystonia due to fibrodysplasia ossificans progressiva (FOP), a connective tissue disorder characterised by heterotopic ossification in muscles, tendons and ligaments. The patient presented with abnormal neck postures suggestive of cervical dystonia and further developed abnormal trunk and limb postures. Considering imaging evidence of inflammation in the sternocleidomastoid muscles, the abnormal postures were characterised within the spectrum of pseudodystonia rather than dystonia. (Source: Parkinsonism and Related Disorders)
Source: Parkinsonism and Related Disorders - January 28, 2020 Category: Neurology Authors: Rok Berlot, Maja Kojovi ć, Kailash P. Bhatia Tags: Correspondence Source Type: research

Fibrodysplasia Ossificans Progressiva (FOP): A Segmental Progeroid Syndrome
Segmental progeroid syndromes are commonly represented by genetic conditions which recapitulate aspects of physiological aging by similar, disparate, or unknown mechanisms. Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease caused by mutations in the gene for ACVR1/ALK2 encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic protein (BMP) type I receptor, and results in the formation of extra-skeletal ossification and a constellation of others features, many of which resemble accelerated aging. The median estimated lifespan of individuals with FOP is approximately 56 years of age. ...
Source: Frontiers in Endocrinology - January 10, 2020 Category: Endocrinology Source Type: research

Is fibrodysplasia ossificans progressiva an interleukin-1 driven auto-inflammatory syndrome?
Fibrodysplasia ossificans progressiva (FOP) is the most catastrophic form of heterotopic ossification, due to ongoing intracellular signaling through the bone morphogenic protein pathway. The paroxysmal appear... (Source: Pediatric Rheumatology)
Source: Pediatric Rheumatology - December 21, 2019 Category: Rheumatology Authors: Ruby Haviv, Veronica Moshe, Fabrizio De Benedetti, Giusi Prencipe, Noa Rabinowicz and Yosef Uziel Tags: Case Report Source Type: research

Fibrodysplasia ossificans progressiva (stone man syndrome): a case report
ConclusionFibrodysplasia ossificans progressiva is a very rare and disabling disorder that, if misdiagnosed, can lead to unnecessary surgical intervention and disastrous results of early disability. We need to spread knowledge to physicians and patients ’ family members about the disease, as well as its features for early diagnosis and how to prevent flare-up of the disease to promote better quality of life in these patients. (Source: Journal of Medical Case Reports)
Source: Journal of Medical Case Reports - December 1, 2019 Category: General Medicine Source Type: research

Inflammation in Fibrodysplasia Ossificans Progressiva and Other Forms of Heterotopic Ossification
AbstractPurpose of reviewHeterotopic ossification (HO) is associated with inflammation. The goal of this review is to examine recent findings on the roles of inflammation and the immune system in HO. We examine how inflammation changes in fibrodysplasia ossificans progressiva, in traumatic HO, and in other clinical conditions of HO. We also discuss how inflammation may be a target for treating HO.Recent findingsBoth genetic and acquired forms of HO show similarities in their inflammatory cell types and signaling pathways. These include macrophages, mast cells, and adaptive immune cells, along with hypoxia signaling pathway...
Source: Current Osteoporosis Reports - November 13, 2019 Category: Orthopaedics Source Type: research

Fibrodysplasia ossificans progressiva: lessons learned from a rare disease
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 - November 7, 2019 Category: Pediatrics Tags: GENETICS: Edited by Nathaniel H. Robin Source Type: research

Generation of Fibrodysplasia ossificans progressiva and control integration free iPSC lines from periodontal ligament fibroblasts
Publication date: Available online 5 November 2019Source: Stem Cell ResearchAuthor(s): G. Sanchez-Duffhues, H. Mikkers, D. de Jong, K. Szuhai, T.J. de Vries, C. Freund, N. Bravenboer, R.J.J. van Es, J.C. Netelenbos, M-J. Goumans, E.M.W. Eekhoff, P ten DijkeAbstractFibrodysplasia ossificans progressiva (FOP) is a very rare devastating heterotopic ossification disorder, classically caused by a heterozygous single point mutation (c.617G>A) in the ACVR1 gene, encoding the Bone morphogenetic protein (BMP) type I receptor, also termed activin receptor-like kinase (ALK)2. FOP patients develop heterotopic ossification episodica...
Source: Stem Cell Research - November 5, 2019 Category: Stem Cells Source Type: research

Analysis of clinical manifestations and treatment in 26 children with fibrodysplasia ossificans progressiva in China.
CONCLUSIONS: FOP is a rare autosomal dominant heritable disease. The main clinical manifestations observed in this study were recurrent inflammatory mass and toe-finger deformity. If the diagnosis and treatment are not performed in a timely manner, serious complications are likely to affect the prognosis. Therefore, early diagnosis and active treatment should be performed. PMID: 31529313 [PubMed - as supplied by publisher] (Source: World Journal of Pediatrics : WJP)
Source: World Journal of Pediatrics : WJP - September 16, 2019 Category: Pediatrics Authors: Zhang JM, Li CF, Ke SY, Piao YR, Han TX, Kuang WY, Wang J, Deng JH, Tan XH, Li C Tags: World J Pediatr Source Type: research

The role of Activin A in Fibrodysplasia Ossificans Progressiva: a prominent mediator.
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 chondroge...
Source: Bioscience Reports - July 24, 2019 Category: Biomedical Science Authors: Lin H, Shi F, Gao J, Hua P Tags: Biosci Rep Source Type: research

Late-onset Fibrodysplasia Ossificans Progressiva with atypical presentation: A case report
We present a case of a 66-year-old woman who had initially presented at age 54 without the hallux valgus deformity or classic-type flare-ups. As there is currently no cure for FOP, management is mainly symptom control. Physicians should still consider FOP if imaging indicates progressive heterotopic ossification in the absence of hallux valgus in an older patient. (Source: Case Reports in Womens Health)
Source: Case Reports in Womens Health - July 19, 2019 Category: OBGYN Source Type: research

Correction to: Natural history of fibrodysplasia ossificans progressiva: cross-sectional analysis of annotated baseline phenotypes
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)
Source: Orphanet Journal of Rare Diseases - May 23, 2019 Category: Internal Medicine Authors: Robert J. Pignolo, Genevi ève Baujat, Matthew A. Brown, Carmen De Cunto, Maja Di Rocco, Edward C. Hsiao, Richard Keen, Mona Al Mukaddam, Kim-Hanh Le Quan Sang, Amy Wilson, Barbara White, Donna R. Grogan and Frederick S. Kaplan Tags: Correction Source Type: research

Fibrodysplasia ossificans progressiva at whole-body low-dose computed tomography
Publication date: Available online 20 May 2019Source: Joint Bone SpineAuthor(s): Amandine Chabernaud Negrier, Thomas Funck-Brentano, Robert Burns, Lokmane Taihi, Valérie Bousson (Source: Joint Bone Spine)
Source: Joint Bone Spine - May 22, 2019 Category: Orthopaedics Source Type: research

Natural history of fibrodysplasia ossificans progressiva: cross-sectional analysis of annotated baseline phenotypes
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)
Source: Orphanet Journal of Rare Diseases - May 3, 2019 Category: Internal Medicine Authors: Robert J. Pignolo, Genevi ève Baujat, Matthew A. Brown, Carmen De Cunto, Maja DiRocco, Edward C. Hsiao, Richard Keen, Mona Al Mukaddam, Kim-Hanh Le Quan Sang, Amy Wilson, Barbara White, Donna R. Grogan and Frederick S. Kaplan Tags: Research Source Type: research

Application of in vitro Drug Metabolism Studies in Chemical Structure Optimization for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)
This study demonstrated the importance of metabolite identification for the discovery of novel and safe drug candidates for the treatment of FOP and helped medicinal chemists steer away from potential metabolic liabilities. Introduction Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder involving progressive and widespread postnatal ossification of soft tissues (Buyse et al., 1995). The heterotopic ossification occurs independently from normal bone and progresses in a well-defined spatial pattern. It forms ribbons, sheets and plates of bone that may fuse the joints of the individual. The ecto...
Source: Frontiers in Pharmacology - April 24, 2019 Category: Drugs & Pharmacology Source Type: research

Current and Emerging Therapeutic Options for the Management of Rare Skeletal Diseases
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 - April 3, 2019 Category: Pediatrics Source Type: research

Current and Emerging Therapeutic Options for the Management of Rare Skeletal Diseases.
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 - April 3, 2019 Category: Pediatrics Authors: Semler O, Rehberg M, Mehdiani N, Jackels M, Hoyer-Kuhn H Tags: Paediatr Drugs Source Type: research

Bis-Heteroaryl Pyrazoles: Identification of Orally Bioavailable Inhibitors of Activin Receptor-Like Kinase-2 (R206H).
Abstract Mutant activin receptor-like kinase-2 (ALK2) was reported to be closely associated with the pathogenesis of fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG), and therefore presents an attractive target for therapeutic intervention. Through in silico virtual screenings and structure-activity relationship studies assisted by X-ray crystallographic analyses, a novel series of bis-heteroaryl pyrazole was identified as potent inhibitors of ALK2 (R206H). Derived from in silico hit compound RK-59638 (6a), compound 18p was identified as a potent inhibitor of ALK2 (R206H) wit...
Source: Chemical and Pharmaceutical Bulletin - March 6, 2019 Category: Drugs & Pharmacology Authors: Sekimata K, Sato T, Sakai N, Watanabe H, Mishima-Tsumagari C, Taguri T, Matsumoto T, Fujii Y, Handa N, Honma T, Tanaka A, Shirouzu M, Yokoyama S, Miyazono K, Hashizume Y, Koyama H Tags: Chem Pharm Bull (Tokyo) Source Type: research

Response to comment on 'Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity'
We respond to concerns expressed by Pacifici and Shore (2019) about a recent paper (Lees-Shepard and Goldhamer, 2018a) in which we reported that the drug palovarotene can have severe side effects in a mouse model of fibrodysplasia ossificans progressiva. (Source: eLife)
Source: eLife - January 30, 2019 Category: Biomedical Science Tags: Human Biology and Medicine Stem Cells and Regenerative Medicine Source Type: research

BMP-dependent, injury-induced stem cell niche as a mechanism of heterotopic ossification
Heterotopic ossification (HO), either acquired (aHO) or hereditary, such as fibrodysplasia ossificans progressiva (FOP), is a serious condition without effective treatment. Understanding of the core process of... (Source: Stem Cell Research and Therapy)
Source: Stem Cell Research and Therapy - January 11, 2019 Category: Stem Cells Authors: Chen Kan, Na Ding, Jiazhao Yang, Zhenya Tan, Tammy L. McGuire, Haimei Lu, Keqin Zhang, Diana M. Palila Berger, John A. Kessler and Lixin Kan Tags: Research Source Type: research

Development process of traumatic heterotopic ossification of the temporomandibular joint in mice
Heterotopic ossification (HO) means the formation of ectopic bone in muscles, tendons, ligaments, and other soft tissues(Amar et al., 2015). HO is divided into acquired nongenetic HO and inherited genetic HO (Xu et al., 2018). For the rare genetic HO, fibrodysplasia ossificans progressiva (FOP) involves endochondral ossification, while progressive osseous heteroplasia (POH) and Albright hereditary osteodystrophy (AHO) leads to HO through intramembranous ossification(Shore and Kaplan, 2010). Neurogenic trauma-induced HO is a common type of acquired nongenetic HO and occurs through both intramembranous and endochondral ossif...
Source: Journal of Cranio-Maxillofacial Surgery - December 3, 2018 Category: ENT & OMF Authors: Yan Zhao, Pengchao Liu, Qiming Chen, Ningjuan Ouyang, Yuheng Lin, Wenbin Zhang, Jiewen Dai, Guofang Shen Source Type: research

An Adult Zebrafish Model of Fibrodysplasia Ossificans Progressiva.
Abstract Fibrodysplasia ossificans progressiva (FOP) is a rare human skeletal disease caused by constitutively activating mutations in the gene ACVR1, which encodes a type I BMP/TGFβ family member receptor. FOP is characterized by progressive heterotopic ossification (HO) of fibrous tissues, including skeletal muscle, tendons, and ligaments, as well as malformation of the big toes, vertebral fusions, and osteochondromas. Surgical interventions in patients often result in enhanced HO, which can exacerbate rather than improve diagnostic outcomes. As a result of these difficulties, a variety of animal models are...
Source: Mol Biol Cell - November 12, 2018 Category: Molecular Biology Authors: LaBonty M, Yelick PC Tags: Methods Mol Biol Source Type: research

The effect of Activin ‐A on periodontal ligament fibroblasts‐mediated osteoclast formation in healthy donors and in patients with fibrodysplasia ossificans progressiva
This study brings new insight on the role of Activin A in osteoclast formation, which may further add to understanding FOP pathophysiology; in addition to the known Activin ‐A‐mediated HO, this study shows that Activin‐A may also inhibit osteoclast formation, thereby further promoting HO formation. (Source: Journal of Cellular Physiology)
Source: Journal of Cellular Physiology - November 11, 2018 Category: Cytology Authors: Ton Schoenmaker, Fenne Wouters, Dimitra Micha, Tim Forouzanfar, Coen Netelenbos, E. Marelise W. Eekhoff, Nathalie Bravenboer, Teun J. de Vries Tags: ORIGINAL RESEARCH ARTICLE Source Type: research

An mTOR Signaling Modulator Suppressed Heterotopic Ossification of Fibrodysplasia Ossificans Progressiva
Publication date: Available online 1 November 2018Source: Stem Cell ReportsAuthor(s): Kyosuke Hino, Chengzhu Zhao, Kazuhiko Horigome, Megumi Nishio, Yasue Okanishi, Sanae Nagata, Shingo Komura, Yasuhiro Yamada, Junya Toguchida, Akira Ohta, Makoto IkeyaSummaryFibrodysplasia ossificans progressiva (FOP) is a rare and intractable disorder characterized by extraskeletal bone formation through endochondral ossification. FOP patients harbor gain-of-function mutations in ACVR1 (FOP-ACVR1), a type I receptor for bone morphogenetic proteins. Despite numerous studies, no drugs have been approved for FOP. Here, we developed a high-th...
Source: Stem Cell Reports - November 2, 2018 Category: Stem Cells Source Type: research

Challenges in the treatment of fibrodysplasia ossificans progressiva
AbstractFibrodysplasia ossificans progressiva (FOP), is a rare autosomal dominant connective tissue disease with a prevalence of 1 in 2 million. It is characterized by congenital foot deformities and multiple heterotopic ossifications in fibrous tissue. It usually starts with painful soft tissue swellings occurring with attacks at the ages of three or four. The attacks develop spontaneously or after minor trauma, and gradually turn into heterotopic ossifications that cause joint limitations, growth defects, skeletal deformities and chronic pain. The average life expectancy is forthy, and most of the patients are lost due t...
Source: Rheumatology International - October 20, 2018 Category: Rheumatology Source Type: research

Special Considerations for Clinical Trials in Fibrodysplasia Ossificans Progressiva (FOP)
British Journal of Clinical Pharmacology,Volume 0, Issue ja, -Not available-. (Source: British Journal of Clinical Pharmacology)
Source: British Journal of Clinical Pharmacology - October 3, 2018 Category: Drugs & Pharmacology Authors: Edward C. Hsiao, Maja Di Rocco, Amanda Cali, Michael Zasloff, Mona Al Mukaddam, Robert Pignolo, Zvi Grunwald, Coen Netelenbos, Richard Keen, Genevieve Baujat, Matthew A. Brown, Tae ‐Joon Cho, Carmen De Cunto, Patricia Delai, Nobuhiko Haga, Source Type: research

Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by debilitating heterotopic ossification (HO). The retinoic acid receptor gamma agonist, palovarotene, and antibody-mediated activin A blockade have entered human clinical trials, but how these therapeutic modalities affect the behavior of pathogenic fibro/adipogenic progenitors (FAPs) is unclear. Using live-animal luminescence imaging, we show that transplanted pathogenic FAPs undergo rapid initial expansion, with peak number strongly correlating with HO severity. Palovarotene significantly reduced expansion of pathogenic FAPs, but was le...
Source: eLife - September 18, 2018 Category: Biomedical Science Tags: Human Biology and Medicine Source Type: research

Difficult airway management in a child with fibrodysplasia ossificans progressiva in status asthmaticus
We present a challenging case of an 11-year-old, 28  kg girl with fibrodysplasia ossificans progressiva. She had severe neck rotation and flexion, kyphosis, scoliosis, decreased chest size (TIS) and extremity contractures. She presented with hypoxia due to parainfluenza virus infection. She became progressively worse requiring continuous nebulized albuterol (1 mg·kg−1·h−1), methylprednisolone, intravenous magnesium, terbutaline infusion, and nasal bilevel positive airway pressure (BiPAP). Approaching respiratory failure, anesthesiology and otolaryngology were consulted to evaluate and secure t...
Source: Journal of Clinical Anesthesia - July 20, 2018 Category: Anesthesiology Authors: Bukola Ojo, Michael Collins, Henry Ou, Sally Rampersad, Daniel Rubens, Lance Patak Tags: Correspondence Source Type: research

Severe trismus and contraindicated exodontia in a patient with fibrodysplasia ossificans progressiva: case report
Publication date: June 2018Source: British Journal of Oral and Maxillofacial Surgery, Volume 56, Issue 5Author(s): A. Geddis-ReganAbstractFibrodysplasia ossificans progressiva is a rare genetic disease of connective tissue in which muscles, ligaments, and tendons ossify either spontaneously or after trauma. Patients can develop physical disabilities and restriction of respiratory function. A patient attended a maxillofacial surgery outpatient clinic with severe trismus and mouth opening limited to 2 mm. The risks of intervention were many from both anaesthetic and surgical perspectives, which prevented the extraction ...
Source: British Journal of Oral and Maxillofacial Surgery - July 10, 2018 Category: ENT & OMF Source Type: research

Fibrodysplasia ossificans progressiva: a current review of imaging findings
ConclusionsRecognition of the imaging manifestations of fibrodysplasia ossificans progressiva is imperative to early diagnosis in order to appropriately direct patient care and preclude unnecessary biopsies or surgical procedures. (Source: Skeletal Radiology)
Source: Skeletal Radiology - June 15, 2018 Category: Radiology Source Type: research

Severe trismus and contraindicated exodontia in a patient with fibrodysplasia ossificans progressiva: case report
Publication date: Available online 3 May 2018 Source:British Journal of Oral and Maxillofacial Surgery Author(s): A. Geddis-Regan Fibrodysplasia ossificans progressiva is a rare genetic disease of connective tissue in which muscles, ligaments, and tendons ossify either spontaneously or after trauma. Patients can develop physical disabilities and restriction of respiratory function. A patient attended a maxillofacial surgery outpatient clinic with severe trismus and mouth opening limited to 2mm. The risks of intervention were many from both anaesthetic and surgical perspectives, which prevented the extraction of carious te...
Source: British Journal of Oral and Maxillofacial Surgery - May 17, 2018 Category: ENT & OMF Source Type: research

A Bizarre Bone Scan of Fibrodysplasia Ossificans Progressiva
A 27-year-old woman had progressive bony ankylosis over both hands since she was 5 years old. Bony ankylosing over the peripheral joints and spine slowly progressed, and scoliosis surgery was performed at age 14. Recently, she developed difficulty walking, changing position, and opening her mouth. A neurologist was consulted and ruled out the suspicion of narcolepsy. Chest CT showed ankylosing spondylitis. A bone scan showed a bizarre pattern with radiouptake to the left maxilla, bilateral sacroiliac joints, left middle third femur, and soft tissue uptake over bilateral arms, legs, and pelvis. Regional radiograph suggested...
Source: Clinical Nuclear Medicine - May 10, 2018 Category: Nuclear Medicine Tags: Interesting Images Source Type: research

Severe trismus and contraindicated exodontia in a patient with fibrodysplasia ossificans progressiva: case report
Fibrodysplasia ossificans progressiva is a rare genetic disease of connective tissue in which muscles, ligaments, and tendons ossify either spontaneously or after trauma. Patients can develop physical disabilities and restriction of respiratory function. A patient attended a maxillofacial surgery outpatient clinic with severe trismus and mouth opening limited to 2mm. The risks of intervention were many from both anaesthetic and surgical perspectives, which prevented the extraction of carious teeth. (Source: The British Journal of Oral and Maxillofacial Surgery)
Source: The British Journal of Oral and Maxillofacial Surgery - May 2, 2018 Category: ENT & OMF Authors: A. Geddis-Regan Tags: Case report Source Type: research

Hypoxia-selective allosteric destabilization of activin receptor-like kinases: A potential therapeutic avenue for prophylaxis of heterotopic ossification
Heterotopic ossification (HO), the pathological extraskeletal formation of bone, can arise from blast injuries, severe burns, orthopedic procedures and gain-of-function mutations in a component of the bone morphogenetic protein (BMP) signaling pathway, the ACVR1/ALK2 receptor serine-threonine (protein) kinase, causative of Fibrodysplasia Ossificans Progressiva (FOP). All three ALKs ( −2, −3, −6) that play roles in bone morphogenesis contribute to trauma-induced HO, hence are well-validated pharmacological targets. (Source: Bone)
Source: Bone - April 4, 2018 Category: Orthopaedics Authors: Guorong Lu, Mary R. Tandang-Silvas, Alyssa C. Dawson, Trenton J. Dawson, Jay C. Groppe Tags: Full Length Article Source Type: research

Acquired and congenital forms of heterotopic ossification: new pathogenic insights and therapeutic opportunities.
Abstract Heterotopic ossification (HO) involves the formation and accumulation of extraskeletal bone tissue at the expense of local tissues including muscles and connective tissues. There are common forms of HO that are triggered by extensive trauma, burns and other bodily insults, and there are also rare congenital severe forms of HO that occur in children with Fibrodysplasia Ossificans Progressiva or Progressive Osseous Heteroplasia. Given that HO is often preceded by inflammation, current treatments usually involve anti-inflammatory drugs alone or in combination with local irradiation, but are not very effectiv...
Source: Current Opinion in Pharmacology - March 31, 2018 Category: Drugs & Pharmacology Authors: Pacifici M Tags: Curr Opin Pharmacol Source Type: research

Heterotopic Ossification: The Keys to the Kingdom
The metamorphosis of one mature tissue into another is one of the rarest and enigmatic events in medicine. When it involves the transformation of soft connective tissues into mature heterotopic bone, the process is called heterotopic ossification (HO). HO is exemplified by two ultra-rare genetic disorders that are progressive and disabling - fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH) - as well as a myriad of more common acquired and sporadic conditions. (Source: Bone)
Source: Bone - March 20, 2018 Category: Orthopaedics Authors: Frederick S. Kaplan, Robert J. Pignolo, Eileen M. Shore Tags: Editorial Source Type: research

Effects of FKBP12 and type II BMP receptors on signal transduction by ALK2 activating mutations associated with genetic disorders
In this study, we characterized the ALK2 mutants R258G, G328V and F246Y, which were identified in patients with severe FOP, DIPG and unusual hereditary skeletal dysplasia, respectively. Both R258G and G328V were gain-of-function mutations, but F246Y was equivalent to wild-type ALK2. (Source: Bone)
Source: Bone - March 15, 2018 Category: Orthopaedics Authors: Aiko Machiya, Sho Tsukamoto, Satoshi Ohte, Mai Kuratani, Mai Fujimoto, Keigo Kumagai, Kenji Osawa, Naoto Suda, Alex N. Bullock, Takenobu Katagiri Tags: Full Length Article Source Type: research

Correction to: Rarely occurring mutation of ACVR1 gene in Moroccan patient with fibrodysplasia ossificans progressiva
AbstractOne of the author ’s name on this article was incorrectly spelled as “Renata Borcciadi”. The correct spelling is “Renata Bocciardi” and is now presented correctly in this article. (Source: Clinical Rheumatology)
Source: Clinical Rheumatology - March 1, 2018 Category: Rheumatology Source Type: research

Difficult diagnosis and genetic analysis of fibrodysplasia ossificans progressiva: a case report
Fibrodysplasia ossificans progressiva (FOP), an ultra-rare and disabling genetic disorder of skeletal malformations and progressive heterotopic ossification, is caused by heterozygous activating mutations in a... (Source: BMC Medical Genetics)
Source: BMC Medical Genetics - February 27, 2018 Category: Genetics & Stem Cells Authors: Shengjie Tian, Jianhua Zhu and Yaogang Lu Tags: Case report Source Type: research

Stem cells and heterotopic ossification: Lessons from animal models
Put most simply, heterotopic ossification (HO) is the abnormal formation of bone at extraskeletal sites. HO can be classified into two main subtypes, genetic and acquired. Acquired HO is a common complication of major connective tissue injury, traumatic central nervous system injury, and surgical interventions, where it can cause significant pain and postoperative disability. A particularly devastating form of HO is manifested in the rare genetic disorder, fibrodysplasia ossificans progressiva (FOP), in which progressive heterotopic bone formation occurs throughout life, resulting in painful and disabling cumulative immobility. (Source: Bone)
Source: Bone - February 4, 2018 Category: Orthopaedics Authors: John B. Lees-Shepard, David J. Goldhamer Tags: Review Article Source Type: research

A case report of mesenteric heterotopic ossification: Histopathologic and genetic findings
Mesenteric heterotopic ossification (MHO) is very rare and occurs in mid- to late-adulthood, usually in the context of prior abdominal surgery. The mechanisms of MHO are unknown. Here we describe the case of a 72-year-old man with MHO. Standard histological staining revealed that MHO occurred through an endochondral process. By comparison to known mutations in genetic conditions of HO such as fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH), DNA sequencing analysis demonstrated the presence of a commonly occurring heterozygous synonymous polymorphism (c.690G>A; E230E) in the causati...
Source: Bone - January 7, 2018 Category: Orthopaedics Authors: Matthew Amalfitano, Billie Fyfe, Sumi V. Thomas, Kevin P. Egan, Meiqi Xu, Andrew G. Smith, Frederick S. Kaplan, Eileen M. Shore, Robert J. Pignolo Tags: Review Article Source Type: research