Review
Biochemistry & Molecular Biology
Fatima Khan, Xiaobing Yu, Edward C. Hsiao
Summary: Fibrodysplasia Ossificans Progressiva (FOP) is an ultra-rare disorder characterized by heterotopic ossifications at extraskeletal sites. It is caused by gain-of-function mutations in the Acvr1/Alk2 gene, leading to severe cardiopulmonary and neurological dysfunctions.
Article
Genetics & Heredity
Daniele De Brasi, Francesca Orlando, Valeria Gaeta, Maria De Liso, Fabio Acquaviva, Luigi Martemucci, Augusto Mastrominico, Maja Di Rocco
Summary: FOP is an ultra-rare genetic condition characterized by extraskeletal bone formation, with activating mutations of the ACVR1 gene being responsible for the skeletal and nonskeletal features. The clinical phenotype includes congenital bilateral hallux valgus malformation and early-onset heterotopic ossification, with essential care interventions focusing on avoiding unnecessary surgeries and administering medications to control inflammation.
Review
Biochemistry & Molecular Biology
Francesc Ventura, Eleanor Williams, Makoto Ikeya, Alex N. Bullock, Peter ten Dijke, Marie-Jose Goumans, Gonzalo Sanchez-Duffhues
Summary: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare congenital disease caused by heterozygous gene point mutations in the ACVR1 gene, leading to ectopic bone formation. Although there is no approved cure for FOP yet, multiple clinical trials are underway to find safe and effective treatments for this condition.
Article
Endocrinology & Metabolism
Robert J. Pignolo, Miriam Kimel, John Whalen, Ariane K. Kawata, Alexander Artyomenko, Frederick S. Kaplan
Summary: This study assessed the reliability and validity of age-specific versions of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) in measuring the impact of FOP on physical function and activities of daily living. The results confirmed that the FOP-PFQ is a reliable and valid measure, demonstrating good internal consistency and test-retest reliability, as well as convergent validity with other assessment measures. Known-groups validity was also demonstrated. However, results for pediatric versions were inconclusive. Overall, the FOP-PFQ is a valuable tool for evaluating individuals with FOP.
Editorial Material
Rheumatology
Carlos Enrique Suarez Acosta, Esperanza Romero Fernandez
Summary: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by progressive disability due to extensive bone formation and malformed big toes. The disease immobilizes joints and renders movement impossible, with no current effective prevention or cure available. Prompt genetic counseling is important in families with FOP due to its autosomal dominant inheritance.
JCR-JOURNAL OF CLINICAL RHEUMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Yeon-Suk Yang, Jung-Min Kim, Jun Xie, Sachin Chaugule, Chujiao Lin, Hong Ma, Edward Hsiao, Jaehyoung Hong, Hyonho Chun, Eileen M. Shore, Frederick S. Kaplan, Guangping Gao, Jae-Hyuck Shim
Summary: The study developed gene therapy approaches that demonstrated efficacy in mouse models and human induced pluripotent stem cells, showing potential for preventing disabling heterotopic ossification in fibrodysplasia ossificans progressiva. These promising treatments could offer significant clinical benefits for patients with this rare genetic disorder.
NATURE COMMUNICATIONS
(2022)
Review
Medicine, General & Internal
Ton Schoenmaker, Amine Dahou Bouchankouk, Semih ozkan, Marjolijn Gilijamse, Elinor Bouvy-Berends, Coen Netelenbos, Frank Lobbezoo, Elisabeth Marelise W. Eekhoff, Teun J. de Vries
Summary: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by abnormal bone formation in the muscles, tendons, and ligaments. This study aimed to evaluate the age of onset and location of bone formation and the resulting functional restrictions in the jaw of FOP patients. The results showed that bone formation is more common in females and trauma-induced bone formation occurs at a younger age than spontaneous bone formation. Additionally, the location of bone formation in the maxillofacial region affects the degree of restriction in jaw movement.
FRONTIERS IN MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Roberto Ravazzolo, Renata Bocciardi
Summary: This article summarizes the basic research on the genetic mutation responsible for FOP, including advancements in related fields and potential therapeutic approaches. It also explores the reasons why the single mutation R206H in the ACVR1 gene is highly prevalent in FOP patients, as well as factors that may modulate FOP expression.
Article
Pediatrics
Ambika Gupta, Puneeta Mishra, Madhumita Roy Chowdhury, Shah Alam Khan, Manisha Jana, Madhulika Kabra, Neerja Gupta
Summary: This study evaluates the natural history of Fibrodysplasia Ossificans Progressiva (FOP) and highlights possible masqueraders causing diagnostic delay and iatrogenic interventions. The findings indicate that clinical suspicion followed by molecular testing is a straightforward and effective method for confirming FOP. Diagnostic delay may result in disease progression and unnecessary invasive interventions.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Review
Biotechnology & Applied Microbiology
Elisabeth M. W. Eekhoff, Ruben D. de Ruiter, Bernard J. Smilde, Ton Schoenmaker, Teun J. de Vries, Coen Netelenbos, Edward C. Hsiao, Christiaan Scott, Nobuhiko Haga, Zvi Grunwald, Carmen L. De Cunto, Maja di Rocco, Patricia L. R. Delai, Robert J. Diecidue, Vrisha Madhuri, Tae-Joon Cho, Rolf Morhart, Clive S. Friedman, Michael Zasloff, Gerard Pals, Jae-Hyuck Shim, Guangping Gao, Frederick Kaplan, Robert J. Pignolo, Dimitra Micha
Summary: Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease where soft connective tissue turns into heterotopic bone. Although the genetic defect is known, effective treatments have been hindered by the complexity of the disease. Gene therapy shows promise as a therapeutic option for FOP, but the role of the immune system and the primary causative cell remain unknown.
HUMAN GENE THERAPY
(2022)
Article
Pediatrics
Joshua Chun Ki Chan, Evelyn Eugenie Kuong, Joyce Pui Kwan Chan, Ho Ming Luk, Jasmine Lee Fong Fung, Joanna Yuet-ling Tung, Brian Hon Yin Chung
Summary: Fibrodysplasia ossificans progressiva (FOP) is a rare condition with challenging diagnosis due to its rarity and non-specific symptoms. Early diagnosis and suitable management are crucial for preserving patients' function and quality of life. This report shares the diagnostic journeys and clinical courses of 8 FOP patients in Hong Kong, highlighting the associated challenges.
FRONTIERS IN PEDIATRICS
(2023)
Article
Biochemistry & Molecular Biology
Yeon-Suk Yang, Chujiao Lin, Hong Ma, Jun Xie, Frederick S. Kaplan, Guangping Gao, Jae-Hyuck Shim
Summary: Gene therapy using adeno-associated virus has been developed to suppress trauma-induced heterotopic ossification in mice with fibrodysplasia ossificans progressiva (FOP), while limiting expression in non-skeletal organs. The therapy effectively inhibits aberrant signaling pathway activation and osteogenic differentiation in skeletal progenitor cells.
Article
Genetics & Heredity
Robert J. Pignolo, Genevieve Baujat, Matthew A. Brown, Carmen De Cunto, Edward C. Hsiao, Richard Keen, Mona Al Mukaddam, Kim-Hanh Le Quan Sang, Amy Wilson, Rose Marino, Andrew Strahs, Frederick S. Kaplan
Summary: This study presents the first prospective, international, natural history study of fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder. The results demonstrate the debilitating effects and progressive nature of FOP, with the most significant progression observed during childhood and early adulthood.
GENETICS IN MEDICINE
(2022)
Article
Genetics & Heredity
Carolyn E. Schwartz, Roland B. Stark, David Cella, Katrina Borowiec, Katherine L. Gooch, Ivana F. Audhya
Summary: This study developed a condition-specific caregiver proxy-report measure for Duchenne Muscular Dystrophy (DMD) utilizing item banks from the PROMIS system, aiming to understand the impact of DMD on caregivers. The study sample included 521 DMD caregivers and showed strong psychometric characteristics in most domains. Future research will focus on assessing the responsiveness and validity of the measure over time and its comparison to DMD patient self-report.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Medicine, Research & Experimental
John B. Lees-Shepard, Sean J. Stoessel, Julian T. Chandler, Keith Bouchard, Patricia Bento, Lorraine N. Apuzzo, Parvathi M. Devarakonda, Jeffrey W. Hunter, David J. Goldhamer
Summary: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by progressive and catastrophic heterotopic ossification (HO). This study found that a monoclonal blocking antibody, JAB0505, exacerbated injury-induced HO in FOP mouse models, raising concerns about its safety and efficacy for treating FOP patients.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
