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FOP: still turning into stone
Abstract Fibrodysplasia ossificans progressiva (FOP) is a rare catastrophic genetic condition of extraskeletal (heterotopic) ossification. One in every two million people is affected worldwide, with no ethnic, racial, gender, or geographic predisposition. Most cases of FOP arise from a spontaneous missense mutation in the gene encoding bone morphogenic protein (BMP) type II receptor (ACVR1/ALK2). Affected individuals are normal at birth apart from malformed great toes. Onset of clinical symptoms is usually in the first decade of life, presenting with episodic emergence of painful rapidly appearing tumor-like soft...
Source: Clinical Rheumatology - January 26, 2015 Category: Rheumatology Source Type: research
Clinical Utility Gene Card for: Fibrodysplasia ossificans progressiva
cesc Ventura, Genevieve Beaujat, Elizabeth M W Eekhoff & Gerard Pals (Source: European Journal of Human Genetics)
Source: European Journal of Human Genetics - January 21, 2015 Category: Genetics & Stem Cells Authors: Nathalie BravenboerDimitra MichaJames T TriffitAlex N BullockRoberto RavazolloRenata BocciardiMaja di RoccoJ Coen NetelenbosPeter Ten DijkeGonzalo Sánchez-DuffhuesFred S KaplanEileen M ShoreRobert J PignoloPetra SeemannFrancesc VenturaGenevieve BeaujatEl Source Type: research
A small molecule targeting ALK1 prevents Notch cooperativity and inhibits functional angiogenesis
Abstract Activin receptor-like kinase 1 (ALK1, encoded by the gene ACVRL1) is a type I BMP/TGF-β receptor that mediates signalling in endothelial cells via phosphorylation of SMAD1/5/8. During angiogenesis, sprouting endothelial cells specialise into tip cells and stalk cells. ALK1 synergises with Notch in stalk cells to induce expression of the Notch targets HEY1 and HEY2 and thereby represses tip cell formation and angiogenic sprouting. The ALK1-Fc soluble protein fusion has entered clinic trials as a therapeutic strategy to sequester the high-affinity extracellular ligand BMP9. Here, we determined the crystal ...
Source: Angiogenesis - January 4, 2015 Category: Molecular Biology Source Type: research
Molecular, Phenotypic Aspects and Therapeutic Horizons of Rare Genetic Bone Disorders.
Abstract A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD) of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossific...
Source: Biomed Res - December 26, 2014 Category: Research Authors: Faruqi T, Dhawan N, Bahl J, Gupta V, Vohra S, Tu K, Abdelmagid SM Tags: Biomed Res Int Source Type: research
Activin Signaling Disruption in the Cochlea Does Not Influence Hearing in Adult Mice
In this study, we present for the first time the presence of activin A and ActRIB in the adult cochlea. Transgenic mice with postnatal dominant-negative ActRIB expression causing disruption of activin signaling in vivo were used for assessing cochlear morphology and hearing ability through the auditory brainstem response (ABR) threshold. Nonfunctioning ActRIB did not affect the ABR thresholds and did not alter the microscopic anatomy of the cochlea. We conclude, therefore, that activin signaling is not necessary for hearing in adult mice under physiological conditions but may be important during and after damaging events i...
Source: Audiology and Neurotology - November 25, 2014 Category: Audiology Source Type: research
Fibrodysplasia Ossificans Progressiva: Clinical Course, Genetic Mutations and Genotype-Phenotype Correlation
Fibrodysplasia ossificans progressiva (FOP, MIM 135100) is a rare autosomal dominant genetic disorder and the most disabling condition of heterotopic (extraskeletal) ossification in humans. Mutations in the ACVR1 gene (MIM 102576) were identified as a genetic cause of FOP [Shore et al., 2006]. Most patients with FOP have the same recurrent single nucleotide change c.617G>A, p.R206H in the ACVR1 gene. Furthermore, 11 other mutations in the ACVR1 gene have been described as a cause of FOP. Here, we review phenotypic and molecular findings of 130 cases of FOP reported in the literature from 1982 to April 2014 and discuss poss...
Source: Molecular Syndromology - November 7, 2014 Category: Molecular Biology Source Type: research
Is “Fibrodysplasia Ossificans Progressiva” a Vascular Disease? A Groundbreaking Pathogenic Model
Publication date: November–December 2014 Source:Reumatología Clínica (English Edition), Volume 10, Issue 6 Author(s): Antonio Morales-Piga , Francisco Javier Bachiller-Corral , Gonzalo Sánchez-Duffhues Fibrodysplasia ossificans progressiva is the most severe and disabling disorder of ectopic ossification in humans. It is characterized by congenital skeletal abnormalities in association with extraskeletal widespread endochondral osteogenesis. Virtually all patients show the same mutation in the “activin A type-I/activin-like kinase-2” receptor encoding gene. As a result of this discovery there have been significa...
Source: Reumatologia Clinica - November 6, 2014 Category: Rheumatology Source Type: research
The type I BMP receptor ACVR1/ALK2 is required for chondrogenesis during development
This article is protected by copyright. All rights reserved (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - November 1, 2014 Category: Orthopaedics Authors: Diana Rigueur, Sean Brugger, Teni Anbarchian, Jong Kil Kim, Yoo Jin Lee, Karen Lyons Tags: Original Article Source Type: research
Clementia begins Phase II extension trial of palovarotene to treat FOP patients
Canada-based Clementia Pharmaceuticals has started a Phase II extension trial of palovarotene, an investigational retinoic acid receptor gamma agonist, to treat patients with fibrodysplasia ossificans progressiva (FOP), a rare and severely disabling … (Source: Drug Development Technology)
Source: Drug Development Technology - October 28, 2014 Category: Pharmaceuticals Source Type: news
Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva
A 7-year-old girl presented with hard, painful lumps over her neck, back, and thighs, which had gradually developed and progressively worsened over the past few years. There was no significant history of trauma. Physical examination revealed smooth, mobile, bony-hard masses, which did not arise from the skeleton. She also had significant neck stiffness, clinodactyly, and hallux valgus (Figure, A). Radiographs revealed prominent ossification of the ligamentum nuchae, fusion of the posterior elements of cervical spine (Figure, B), and a band-like angular area of heterotopic ossification (HO) over the left lower hemithorax an...
Source: The Journal of Pediatrics - October 24, 2014 Category: Pediatrics Authors: Akshay Sharma, Miriam Behar Tags: Insights and Images Source Type: research
Fibrodysplasia ossificans progressiva: bilateral hallux valgus on ultrasound a clue for the first prenatal diagnosis for this condition –clinical report and review of the literature
We present the first case of prenatal diagnosis of fibrodysplasia ossificans progressiva.Fetal bilateral hallux valgus, seen on second‐trimester ultrasound prompted the clinicians to consider this diagnosis even though family history was negative for FOP. The fetus had the recurrent c.617G>A mutation in ACVR1 gene.This case illustrates that FOP should be considered in the differential diagnosis of fetal hallux valgus to provide appropriate genetic counseling. (Source: Prenatal Diagnosis)
Source: Prenatal Diagnosis - October 1, 2014 Category: Perinatology & Neonatology Authors: Catalina Maftei, Françoise Rypens, Isabelle Thiffault, Johanne Dubé, Anne‐Marie Laberge, Emmanuelle Lemyre Tags: Research Letter Source Type: research
The girl whose joints and muscles are turning to STONE: Horrific rare condition causes sufferers to become imprisoned in a second skeleton - which eventually suffocates them
Ni Min, 14, from China's Sichuan Province, suffers from the condition fibrodysplasia ossificans progressiva (FOP), also dubbed 'stone man' syndrome. (Source: the Mail online | Health)
Source: the Mail online | Health - September 25, 2014 Category: Consumer Health News Source Type: news
Genes, Vol. 5, Pages 792-803: The Revolution in Human Monogenic Disease Mapping
The successful completion of the Human Genome Project (HGP) was an unprecedented scientific advance that has become an invaluable resource in the search for genes that cause monogenic and common (polygenic) diseases. Prior to the HGP, linkage analysis had successfully mapped many disease genes for monogenic disorders; however, the limitations of this approach were particularly evident for identifying causative genes in rare genetic disorders affecting lifespan and/or reproductive fitness, such as skeletal dysplasias. In this review, we illustrate the challenges of mapping disease genes in such conditions through the ultra-...
Source: Genes - September 5, 2014 Category: Genetics & Stem Cells Authors: Emma DuncanMatthew BrownEileen Shore Tags: Review Source Type: research
Relationship of 3,5-Diaryl-2-aminopyridine
ALK2 Inhibitors Reveals Unaltered Binding Affinity for Fibrodysplasia
Ossificans Progressiva Causing Mutants
Journal of Medicinal ChemistryDOI: 10.1021/jm501177w (Source: Journal of Medicinal Chemistry)
Source: Journal of Medicinal Chemistry - September 4, 2014 Category: Chemistry Authors: Agustin H. Mohedas, You Wang, Caroline E. Sanvitale, Peter Canning, Sungwoon Choi, Xuechao Xing, Alex N. Bullock, Gregory D. Cuny and Paul B. Yu Source Type: research
ACVR1 in FOP and DIPG
Whole-genome sequencing studies have recently identified a quarter of cases of the rare childhood brainstem tumor diffuse intrinsic pontine glioma to harbor somatic mutations in ACVR1. This gene encodes the type I bone morphogenic protein receptor ALK2, with the residues affected identical to those that, when mutated in the germline, give rise to the congenital malformation syndrome fibrodysplasia ossificans progressiva (FOP), resulting in the transformation of soft tissue into bone. This unexpected link points toward the importance of developmental biology processes in tumorigenesis and provides an extensive experience in...
Source: Cancer Research - September 1, 2014 Category: Cancer & Oncology Authors: Taylor, K. R., Vinci, M., Bullock, A. N., Jones, C. Tags: Review Source Type: research
Clementia begins Phase II trial of palovarotene to treat fibrodysplasia ossificans progressiva
Canada-based Clementia Pharmaceuticals has started a double-blind, placebo-controlled Phase II clinical trial of palovarotene to treat fibrodysplasia ossificans progressiva (FOP), a rare, severely disabling genetic disease. (Source: Drug Development Technology)
Source: Drug Development Technology - July 14, 2014 Category: Pharmaceuticals Source Type: news
ALK2 Signaling Enhances Osteoclast Formation [Molecular Bases of Disease]
In conclusion, this study demonstrated that the causal mutation transfection of fibrodysplasia ossificans progressiva in myoblasts enhanced the formation of osteoclasts from its precursor through TGF-β in muscle tissues. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - June 12, 2014 Category: Chemistry Authors: Yano, M., Kawao, N., Okumoto, K., Tamura, Y., Okada, K., Kaji, H. Tags: Cell Biology Source Type: research
Evaluation of the Cellular Origins of Heterotopic Ossification.
Abstract EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Update the current knowledge about candidate cell populations as heterotopic ossification (HO) contributors. 2. Understand the potential limitations of the experimental designs and techniques underlying the identification of putative HO contributors. 3. Clarify the confusion about the phenotypes of candidate populations in the literature. 4. Contrast the fundamental cellular differences between HO and normal skeletogenesis to identify potential disease-specific targets. Heterotopic ossification (HO), acquired or he...
Source: Orthopedics - May 1, 2014 Category: Orthopaedics Authors: Kan L, Kessler JA Tags: Orthopedics Source Type: research
Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma
We report the identification of recurrent activating mutations in the ACVR1 gene, which encodes a type I activin receptor serine/threonine kinase, in 21% of DIPG samples. Strikingly, these somatic mutations (encoding p.Arg206His, p.Arg258Gly, p.Gly328Glu, p.Gly328Val, p.Gly328Trp and p.Gly356Asp substitutions) have not been reported previously in cancer but are identical to mutations found in the germ line of individuals with the congenital childhood developmental disorder fibrodysplasia ossificans progressiva (FOP) and have been shown to constitutively activate the BMP–TGF-β signaling pathway. These mutations r...
Source: Nature Genetics - April 6, 2014 Category: Genetics & Stem Cells Authors: Kathryn R TaylorAlan MackayNathalène TruffauxYaron S ButterfieldOlena MorozovaCathy PhilippeDavid CastelCatherine S GrassoMaria VinciDiana CarvalhoAngel M CarcabosoCarmen de TorresOfelia CruzJaume MoraNatacha Entz-WerleWendy J IngramMichelle MonjeDarren Tags: Letter Source Type: research
Clinical Aspects And Conservative Dental Management of a Patient With Fibrodysplasia Ossificans Progressiva
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by skeletal malformations and ectopic ossifications in skeletal muscles, tendons, ligaments, and aponeurosis. Exacerbation of these ossifications can be caused by dental treatment. Man, 26, with a diagnosis of FOP was referred for dental treatment. Conservative dental procedures, such as oral hygiene instructions and recurrent topical fluoride applications, were performed in addition to endodontic and restorative treatments. Brief dental appointments were conducted without using regional anesthesia or dental dam clamps. The dental chair was...
Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics - January 21, 2014 Category: ENT & OMF Authors: CLARISSA PESSOA FERNANDES, FRANCISCO ARTUR FORTE OLIVEIRA, MALENA REGINA FREITAS E SILVA, RENATA VERAS CARVALHO MOURÃO OKA, CAMILA CARVALHO DE OLIVEIRA, MÁRIO ROGÉRIO LIMA MOTA, ANA PAULA NEGREIROS NUNES ALVES Tags: Online Only Articles Source Type: research
Stem cells used to model disease that causes abnormal bone growth (EurekAlert, 7 January 2014)
A US-Japan study published in the Orphanet Journal of Rare Diseases uses stem cells obtained from patients with the rare genetic condition fibrodysplasia ossificans progressiva to model abnormal bone growth, which the authors suggest could also model similar destructive processes occuring following major trauma. Full article (Source: Society for Endocrinology)
Source: Society for Endocrinology - January 9, 2014 Category: Endocrinology Source Type: news
[Erratum]A Correction to the Editors' Choice Summary Titled "Keeping Bone Where Bone Belongs" by Leslie K. Ferrarelli
Activating mutations in GNAS were mistakenly attributed as causing fibrodysplasia ossificans progressiva, instead of fibrous dysplasia. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - December 18, 2013 Category: Science Authors: Nancy Gough (mailto:ngough at aaas.org) Source Type: news
Induced pluripotent stem cells from patients with human fibrodysplasia ossificans progressiva show increased mineralization and cartilage formation
Conclusions: Our findings establish a FOP disease cell model for in vitro experimentation and provide a proof-of-concept for using human iPS cell models to understand human skeletal disorders. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - December 9, 2013 Category: Internal Medicine Authors: Yoshihisa MatsumotoYohei HayashiChristopher SchlieveMakoto IkeyaHannah KimTrieu NguyenSalma SamiShiro BabaEmilie BarruetAkira NasuIsao AsakaTakanobu OtsukaShinya YamanakaBruce ConklinJunya ToguchidaEdward Hsiao Source Type: research
Fibrodysplasia ossificans progressiva presenting as a neck mass
(Source: International Journal of Pediatric Otorhinolaryngology)
Source: International Journal of Pediatric Otorhinolaryngology - December 1, 2013 Category: ENT & OMF Tags: Abstracts Source Type: research
Fibrodysplasia ossificans progressiva: a case report.
Abstract Fibrodysplasia ossificans progressiva or myositis ossificans is a rare disease characterised by bony deposits or the ossification of soft tissues. It transforms skeletal muscles, tendons, ligaments, fascia, and aponeuroses into heterotopic bony deposits through an endochondral process. This leads to progressive immobility; patients are usually wheelchair-bound by the second decade of life and die of thoracic insufficiency by the fourth decade of life. There is no treatment apart from symptomatic treatment with steroids during flare-ups. Excision of heterotopic ossification is not recommended as it can prov...
Source: Journal of Orthopaedic Surgery - December 1, 2013 Category: Orthopaedics Authors: Dhamangaonkar AC, Tawari AA, Goregaonkar AB Tags: J Orthop Surg (Hong Kong) Source Type: research
ACVR1 (587T>C) mutation in a variant form of fibrodysplasia ossificans progressiva: Second report
We report on the second patient worldwide with ACVR1 (587T>C) mutation. A 22‐year‐old Japanese male with no family history of heterotopic ossification did not show any malformation of the great toes and showed normal development from birth to the age of 17 years, when heterotopic ossification appeared in the lumbar area. The clinical symptoms were similar to those reported previously: the delayed onset with a slower and mild clinical course and little finger camptodactyly. Gene analysis revealed that the patient was heterozygous for ACVR1 (587T>C) mutation, the same one as reported in 2011, suggesting a correlati...
Source: American Journal of Medical Genetics Part A - November 20, 2013 Category: Genetics & Stem Cells Authors: Y. Nakahara, T. Katagiri, N. Ogata, N. Haga Tags: Clinical Report Source Type: research
The phenotype and genotype of fibrodysplasia ossificans progressiva in China: A report of 72 cases
Abstract: Fibrodysplasia ossificans progressiva, an ultra-rare and disabling genetic disorder of skeletal malformations and progressive heterotopic ossification (HO), is the most catastrophic condition of skeletal metamorphosis in humans. We studied 72 patients with FOP in China and analyzed their phenotypes and genotypes comprising the world's largest ethnically homogeneous population of FOP patients. Ninety-nine percent of patients (71/72 cases) were of Han nationality; and 1% of patients (1/72 cases) were of Hui nationality. Based on clinical examination, 92% of patients (66/72 cases) had classic FOP; 4% of patients (3/...
Source: Bone - November 1, 2013 Category: Orthopaedics Authors: Wei Zhang, Keqin Zhang, Lige Song, Jing Pang, Hongxing Ma, Eileen M. Shore, Frederick S. Kaplan, Peijun Wang Tags: Original Articles Source Type: research
Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: an open-labeled clinical trial
Conclusions: We could not prove the efficacy of oral Pex administration in the prevention of heterotopic ossifications in FOP. Serum levels of ALP and BAP appear to be promising biomarkers for monitoring the development of ectopic ossifications and efficacy of the therapy. Quantification of change in the total bone volume by whole body CT scanning could be a reliable evaluation tool for disease progression in forthcoming clinical trials of FOP. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - October 16, 2013 Category: Internal Medicine Authors: Hiroshi KitohMasataka AchiwaHiroshi KanekoKenichi MishimaMasaki MatsushitaIzumi KadonoJohn HorowitzBenedetta SallustioKinji OhnoNaoki Ishiguro Source Type: research
Identification and characterization of regulatory elements in the promoter of ACVR1, the gene mutated in Fibrodysplasia Ossificans Progressiva
Conclusions: Our results showed that several transcription factors such as Egr-1, Egr-2, ZBTB7A/LRF, and Hey1, regulate the ACVR1 promoter by binding to the -762/-308 region, which is essential to confer maximal transcriptional activity. The Sp1 transcription factor acts at the most proximal promoter segment upstream of the transcription start site. We observed significant differences in different cell types suggesting tissue specificity of transcriptional regulation. These findings provide novel insights into the molecular mechanisms that regulate expression of the ACVR1 gene and that could be targets of new strategies fo...
Source: Orphanet Journal of Rare Diseases - September 18, 2013 Category: Internal Medicine Authors: Francesca GiacopelliSerena CappatoLaura TonachiniMarzia MuraSimona Di LascioDiego FornasariRoberto RavazzoloRenata Bocciardi Source Type: research
Fibrodysplasia ossificans progressiva presenting as a neck mass
Abstract: Objective: To report a case of fibrodysplasia ossificans progressiva (FOP) initially presenting as a neck mass and alert the practicing otolaryngologist to the imperative to avoid harmful biopsy.Case: A 2-year-old male presented with a firm left posterior neck mass and bilateral great toe malformations. Imaging was non-diagnostic and after 2 weeks of antibiotics the lesion was larger. At surgical biopsy, the mass was pale, firm, and avascular. Histopathology showed low grade fibromyxoid tissue. Rheumatology service diagnosed FOP based on clinical examination of neck mass, bilateral great toe deformities, stiff jo...
Source: International Journal of Pediatric Otorhinolaryngology Extra - September 9, 2013 Category: ENT & OMF Authors: Robert J. Tibesar, Lindsay Eisler, Mona M. LaPlant, James D. Sidman Tags: Case reports Source Type: research
Girl, 17, battling rare disease that turns muscle into a second skeleton and will turn her into a living STATUE
Seanie Nammock, from West London, is suffering from fibrodysplasia ossificans progressiva (FOP), a condition that is turning her muscle and tendon into bone. (Source: the Mail online | Health)
Source: the Mail online | Health - July 29, 2013 Category: Consumer Health News Source Type: news
The skeleton in the closet.
Abstract The origins of fibrodysplasia ossificans progressiva (FOP) in human history are unknown but the condition has been well described since Freke's account in 1740. Important contributions by physicians and scientists in the past two and a half centuries have converged on the remarkable skeleton of Harry Eastlack at The Mutter Museum of The College of Physicians in Philadelphia. PMID: 23810943 [PubMed - as supplied by publisher] (Source: Gene)
Source: Gene - June 25, 2013 Category: Genetics & Stem Cells Authors: Kaplan FS Tags: Gene Source Type: research
Treatment of an intractable cutaneous ulcer in the right lateral malleolus in fibrodysplasia ossificans progressiva.
Abstract Abstract is missing (Letter). PMID: 23722929 [PubMed - as supplied by publisher] (Source: Acta Dermato-Venereologica)
Source: Acta Dermato-Venereologica - May 27, 2013 Category: Dermatology Authors: Matsuda K, Goto M, Ito Y, Shimizu F, Hatan Y, Fujiwara S Tags: Acta Derm Venereol Source Type: research
Fibrodysplasia ossificans progressiva: diagnosis in primary care
OBJETIVO: Buscou-se demonstrar ser possível diagnosticar a fibrodisplasia ossificante progressiva na atenção primária à saúde. DESCRIÇÃO DO CASO: Paciente de dez anos que, desde os quatro anos, mostrava rigidez progressiva nas articulações e na coluna vertebral, além de ossificações de partes moles, muitas vezes associadas a traumatismos. Havia desvio de hálux valgo dos primeiros artelhos de ambos os pés, presente desde o nascimento. Por meio de radiografias, demonstrou-se a presença de ossificações heterotópicas. COMENTÁRIOS: É possível realizar o diagnóstico desta doença com recursos disponíveis ...
Source: Revista Paulista de Pediatria - April 26, 2013 Category: Pediatrics Source Type: research
Imaging diagnosis: fibrodysplasia ossificans progressiva in a cat
A 1‐year‐old female cat was presented for progressive alopecia, gait abnormalities, and stiffness. Radiography demonstrated multiple calcified lesions within the soft tissues of the cervical and thoracic spine, shoulder, and limbs. Postmortem computed tomography provided more detailed information on the distribution, pattern, and extension of lesions. In addition, computed tomography helped guide sample selection for histopathology. The final diagnosis was fibrodysplasia ossificans progressiva. This is a rare disorder of unknown etiology, characterized by fibrosis and heterotopic bone formation in connective tissues. T...
Source: Veterinary Radiology and Ultrasound - April 11, 2013 Category: Veterinary Research Authors: Andrea Klang, Sibylle Kneissl, Romana Glänzel, Andrea Fuchs‐Baumgartinger Tags: Imaging Diagnosis Source Type: research
Fibrodysplasia ossificans progressiva (FOP): Report of a case with extra-articular ankylosis of the mandible
This report outlines the management of a patient with FOP limited to the maxillofacial region where the FOP lesion produced a fusion between the mandibular ramus and the zygomatic complex and trismus. The patient underwent three surgical procedures and various medical treatments during a 19-year period in attempts to manage the trismus, all in vain. The initial difficulty in establishing the diagnosis and ignorance of the true nature of the disease led to unsuccessful surgery. (Source: Journal of Cranio-Maxillofacial Surgery)
Source: Journal of Cranio-Maxillofacial Surgery - March 18, 2013 Category: ENT & OMF Authors: R.K. Kriegbaum, S. Hillerup Source Type: research
Fibrodysplasia ossificans progressiva (FOP): A disorder of extraskeletal endochondral ossification
Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder in which extraskeletal bone forms in soft connective tissues, initiating during childhood and continuing throughout adult life. This heterotopic bone is qualitatively normal and forms through endochondral ossification. Episodes of bone formation often occur in response to injury. In addition to heterotopic ossification, FOP is associated with altered skeletal development, the most characteristic of which is malformation of the great toes. All FOP patients that we have examined carry mutations in ACVR1, the gene encoding the ALK2 BMP type I receptor. Most pat...
Source: Seminars in Arthritis and Rheumatism - February 11, 2013 Category: Rheumatology Authors: Eileen M. Shore Tags: Conference Proceedings Source Type: research
[Is there a place in primary care for rare diseases? The case of fibrodysplasia ossificans progressiva.]
Abstract Fibrodysplasia ossificans progressiva is one of the most devastating constitutional diseases of the bone, and may be a valid example to establish the role of Primary Care in the care of rare diseases. Although rare diseases usually present with marked anomalies, they can mimic signs and symptoms of common disorders, with the risk of going unnoticed. For this reason, all health professionals should proceed with a reasonable suspicion when confronted with a patient with an apparently common disease with atypical symptoms and a non-conventional progress. The care given by the Primary Care team along with othe...
Source: Atencion Primaria - January 28, 2013 Category: Primary Care Authors: Morales-Piga A, García Ribes M, Arribas Álvaro P, Casado Álvaro C, Posada de La Paz M, Bachiller-Corral J Tags: Aten Primaria Source Type: research
Genetic abnormalities in Fibrodysplasia Ossificans Progressiva.
Abstract Fibrodysplasia ossificans progressiva (FOP), characterized by congenital malformation of bones, is an autosomal dominant disorder. This is a rare genetic disorder and its worldwide prevalence is approximately 1/2,000,000. There is no ethnic, racial, gender, or geographic predilection to FOP. It is regarded as one of the intractable disorders, which is not only an extremely disabling disease but also a condition of considerably shortened lifespan. Although the genetic defects of FOP are not completely known, several clinical and animal model studies have implicated that mutations in bone morphogenetic prote...
Source: Genes and Genetic Systems - December 24, 2012 Category: Genetics & Stem Cells Authors: Miao J, Zhang C, Wu S, Peng Z, Tania M Tags: Genes Genet Syst Source Type: research
Intrathoracic Fibrodysplasia Ossificans Progressiva.
Abstract Fibrodysplasia ossificans progressiva is an extremely rare disease that is usually seen in the form of sporadic cases and seems to be localized outside of the thoracic cavity. Inflammation and trauma are accused in the etiology, and too many diagnostic mistakes are done. The disease, which may present genetic transmission and has not a definitive treatment, was seen as an intrathoracic mass for the first time. Intrathoracic mass was excised, and the cure was achieved in our patient, who was defined to be sporadic as a result of familial screening. PMID: 23196878 [PubMed - as supplied by publisher] (Sou...
Source: The Thoracic and Cardiovascular Surgeon - November 29, 2012 Category: Cardiovascular & Thoracic Surgery Authors: Ozkan S, Alp E, Demirağ F, Yazıcı U, Karaoğlanoğlu N Tags: Thorac Cardiovasc Surg Source Type: research
Structural Insights into ALK2 Activation in FOP [Molecular Bases of Disease]
Bone morphogenetic protein (BMP) receptor kinases are tightly regulated to control development and tissue homeostasis. Mutant receptor kinase domains escape regulation leading to severely degenerative diseases and represent an important therapeutic target. Fibrodysplasia ossificans progressiva (FOP) is a rare but devastating disorder of extraskeletal bone formation. FOP-associated mutations in the BMP receptor ALK2 reduce binding of the inhibitor FKBP12 and promote leaky signaling in the absence of ligand. To establish structural mechanisms of receptor regulation and to address the effects of FOP mutation, we determined th...
Source: Journal of Biological Chemistry - October 26, 2012 Category: Chemistry Authors: Chaikuad, A., Alfano, I., Kerr, G., Sanvitale, C. E., Boergermann, J. H., Triffitt, J. T., von Delft, F., Knapp, S., Knaus, P., Bullock, A. N. Tags: Protein Structure and Folding Source Type: research
Clinically applicable antianginal agents suppress osteoblastic transformation of myogenic cells and heterotopic ossifications in mice
Abstract Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by progressive heterotopic ossification. FOP is caused by a gain-of-function mutation in ACVR1 encoding the bone morphogenetic protein type II receptor, ACVR1/ALK2. The mutant receptor causes upregulation of a transcriptional factor, Id1. No therapy is available to prevent the progressive heterotopic ossification in FOP. In an effort to search for clinically applicable drugs for FOP, we screened 1,040 FDA-approved drugs for suppression of the Id1 promoter activated by the mutant ACVR1/ALK2 in C2C12 cells. ...
Source: Journal of Bone and Mineral Metabolism - September 25, 2012 Category: Orthopaedics Tags: Journal of Bone and Mineral Metabolism Source Type: research
The complex craniofacial signature of fibrodysplasia ossificans progressiva: Whose handwriting is it?
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - September 17, 2012 Category: Genetics & Stem Cells Authors: Peter Hammond, Michael Suttie, Raoul C. Hennekam, Judith Allanson, Eileen M. Shore, Frederick S. Kaplan Tags: Correspondence Source Type: research
The signature of craniofacial deformation in fibrodysplasia ossificans progressiva
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - September 17, 2012 Category: Genetics & Stem Cells Authors: Daniel Rocha Carvalho, Luciano Farage, Carlos Eduardo Speck‐Martins Tags: Correspondence Source Type: research
T.O.2 Allele-specific silencing against the ALK2 mutants, R206H and G356D, in fibrodysplasia ossificans progressiva (FOP)
Abstract: Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant congenital disorder characterized by postnatal progressive heterotopic ossification in soft tissues, especially skeletal muscle. In FOP, acute heterotopic ossification is induced by muscle injury, such as accidental trauma or surgical operations. Currently, no definitive treatment exists for FOP. The activin receptor type IA/ activin-like kinase 2 (ACVR1/ALK2) gene has been identified as the responsible gene for both familial and sporadic cases of FOP, and disease-associated ALK2 mutations have been found. ALK2 protein, which is one of the signa...
Source: Neuromuscular Disorders - August 31, 2012 Category: Neurology Authors: H. Furuya, M. Takahashi, T. Katagiri, H. Hohjoh Source Type: research
The danger of biopsy in fibrodysplasia ossificans progressiva
A 2-year-old girl presented with episodic soft tissue swellings for over a year and polyarticular stiffness for half a year. The swellings were painful and mainly involved her head, neck and back region (figure 1). Her neck and shoulders had very limited mobility. Malformations of the great toes were discovered during the physical examination (figure 2). The biopsy of the cephalic swelling done in the local hospital suggested aggressive juvenile fibromatosis, but the swelling enlarged rapidly immediately after the biopsy (figure 3). Fibrodysplasia ossificans progressiva (FOP) was suspected, and the diagnosis was confirmed ...
Source: Archives of Disease in Childhood - August 30, 2012 Category: Pediatrics Authors: Zan, X., Wang, J., You, C. Tags: Miscellaneous Source Type: research
Fibrodysplasia ossificans progressiva in Spain: epidemiological, clinical, and genetic aspects
We report the characteristics of FOP in an endogenous Spanish population. ► The majority of “classic FOP” cases display the c.617G>A mutation in the ACVR1 gene. ► Genotype-phenotype correlation exists between ACVR1 mutations and clinical traits. (Source: Bone)
Source: Bone - August 1, 2012 Category: Orthopaedics Authors: A. Morales-Piga, J. Bachiller-Corral, M.J. Trujillo-Tiebas, A. Villaverde-Hueso, M.L. Gamir-Gamir, V. Alonso-Ferreira, M. Vázquez-Díaz, M. Posada de la Paz, C. Ayuso-García Tags: Articles Source Type: research
Fibrodysplasia ossificans progressiva in Spain: epidemiological, clinical, and genetic aspects
Source: Bone - August 1, 2012 Category: Orthopaedics Authors: A. Morales-Piga, J. Bachiller-Corral, M.J. Trujillo-Tiebas, A. Villaverde-Hueso, M.L. Gamir-Gamir, V. Alonso-Ferreira, M. Vázquez-Díaz, M. Posada de la Paz, C. Ayuso-García Source Type: research
Fibrodysplasia ossificans progressiva in Spain: epidemiological, clinical, and genetic aspects
We aimed to investigate the epidemiological determinants, clinical features, and genetic pattern of FOP in our country by evaluating the entire population of patients identified according to a combination of methods. To achieve this, 24 individuals were confirmed as FOP cases, 17 of whom were alive at the end of 2011 (point prevalence=0.36×10−6). The gender distribution (male/female ratio=13/11) and the concurrent range of ages (from 4 to 53years; mean±SD: 30.2±13.8) are in agreement with similar reports. (Source: Bone)
Source: Bone - August 1, 2012 Category: Orthopaedics Authors: A. Morales-Piga, J. Bachiller-Corral, M.J. Trujillo-Tiebas, A. Villaverde-Hueso, M.L. Gamir-Gamir, V. Alonso-Ferreira, M. Vázquez-Díaz, M. Posada de la Paz, C. Ayuso-García Tags: Original Full Length Article Source Type: research