scholarly journals Congenital Malformation of The Great Toe in Children. Did You Exclude Fibrodysplasia Ossificans Progressiva – FOP.

2021 ◽  
Author(s):  
Maria Kirstine Møller - Madsen ◽  
Darko Antičević
Keyword(s):  
Congenital Malformation ◽  
Genetic Disorder ◽  
Joint Stiffness ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Great Toe ◽  
Therapeutic Approaches ◽  
Dna Test ◽  
Growth Defects ◽  
Minor Injuries ◽  
Conventional Radiology

Abstract Background: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare and severely disabling genetic disorder. The worldwide prevalence is approximately 1 per 2 million. Heterozygous mutations in ACVR1/ALK2 gene exist in all sporadic and familial cases of FOP. The primary aim of this study is to describe the clinical course of three children suffering from FOP and followed for fifteen, twenty-two and forty years, respectively Secondary aim is to provide clinical advice on how to diagnose the condition with special reference to the great toes malformation and give current best therapeutic approaches.Results: All three cases characterized with malformed great toes initially followed by progressive loss of mobility for a period from fifteen to forty years. Conventional radiology indicates the diagnosis and RNA/DNA test confirm it.Conclusion: Congenital malformation of the great toes in early childhood may be the first clinical sign of FOP. A devastating disease due to its progressive formation of heterotopic ossifications in soft tissue even after minor injuries. Leading to progressive immobility, skeletal deformities, chronic pain, growth defects and disabling joint stiffness. No curative treatment exists today. Management is symptomatic combined with a prophylactic lifestyle avoiding blunt and pointed trauma including surgery.

Conductive Hearing Loss in Individuals with Fibrodysplasia Ossificans Progressiva

1999 ◽  
Vol 8 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Charles E. Levy ◽  
Albert T. Lash ◽  
Hal B. Janoff ◽  
Frederick S. Kaplan
Keyword(s):  
Hearing Loss ◽  
Heterotopic Ossification ◽  
Congenital Malformation ◽  
Large Scale ◽  
Soft Tissues ◽  
Conductive Hearing Loss ◽  
Genetic Disorder ◽  
Postal Survey ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Conductive Hearing

Fibrodysplasia ossificans progressiva (FOP) is a very rare genetic disorder that is characterized by progressive heterotopic ossification of soft tissues and congenital malformation of the great toes. Although previous case studies have reported hearing loss in individuals with FOP, there have been no large-scale studies regarding the nature or cause of the hearing loss. Here, we report the findings of a two-part study. In Part I, we report the findings of a postal survey regarding hearing loss that was sent to 102 individuals with FOP. In Part II, we report the findings of on-site hearing evaluations of eight individuals with FOP. The findings of both studies indicate that individuals with FOP are at risk for hearing loss and that the type of loss is predominantly conductive in nature, similar to that seen in individuals who have otosclerosis.

scholarly journals Editorial of Special Issue “Fibrodysplasia Ossificans Progressiva: Studies on Disease Mechanism towards Novel Therapeutic Approaches”

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 140
Author(s):  
Roberto Ravazzolo
Keyword(s):  
Genetic Disorder ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Special Issue ◽  
Therapeutic Approaches ◽  
Disease Mechanism ◽  
Rare Genetic Disorder ◽  
Review Articles ◽  
Novel Therapeutic

The Special Issue on “Fibrodysplasia Ossificans Progressiva: Studies on Disease Mechanism towards Novel Therapeutic Approaches” has published interesting and useful review articles and original experimental articles on fibrodysplasia ossificans progressiva (FOP), a very rare genetic disorder for which much effort is being devoted to search for a cure. In this editorial, I briefly cite the essential content of all the published articles.

scholarly journals The Developmental Phenotype of the Great Toe in Fibrodysplasia Ossificans Progressiva

2020 ◽  
Vol 8 ◽  
Author(s):  
O. Will Towler ◽  
Frederick S. Kaplan ◽  
Eileen M. Shore
Keyword(s):  
Embryonic Development ◽  
Genetic Disorder ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Great Toe ◽  
Ectopic Ossification ◽  
High Prevalence ◽  
Skeletal Formation ◽  
Benign Nature ◽  
Ossification Centers ◽  
Developmental Features

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder in which extensive heterotopic ossification (HO) begins to form during early childhood and progresses throughout life. Although HO does not occur during embryonic development, children who carry the ACVR1R206H mutation that causes most cases of FOP characteristically exhibit malformation of their great toes at birth, indicating that the mutation acts during embryonic development to alter skeletal formation. Despite the high prevalence of the great toe malformation in the FOP population, it has received relatively little attention due to its clinically benign nature. In this study, we examined radiographs from a cohort of 41 FOP patients ranging from 2 months to 48 years of age to provide a detailed analysis of the developmental features, progression, and variability of the great toe malformation of FOP, which include absent skeletal structures, malformed epiphyses, ectopic ossification centers, malformed first metatarsals and phalangeal fusion.

The congenital great toe malformation of fibrodysplasia ossificans progressiva? - A close call

2017 ◽  
Vol 60 (7) ◽  
pp. 399-402 ◽  
Author(s):  
O. Will Towler ◽  
Eileen M. Shore ◽  
Meiqi Xu ◽  
Abbey Bamford ◽  
Ilse Anderson ◽  
...  
Keyword(s):  
Fibrodysplasia Ossificans Progressiva ◽  
Great Toe ◽  
Close Call

Neuroinflammation in Huntington’s disease: A starring role for astrocyte and microglia

2021 ◽  
Vol 19 ◽  
Author(s):  
Julieta Saba ◽  
Federico López Couselo ◽  
Julieta Bruno ◽  
Lila Carniglia ◽  
Daniela Durand ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Genetic Disorder ◽  
Cag Repeat ◽  
Inflammatory Factors ◽  
Therapeutic Approaches ◽  
Reactive Microglia ◽  
New Treatments ◽  
The Brain

: Huntington’s disease (HD) is a neurodegenerative genetic disorder caused by a CAG repeat expansion in the huntingtin gene. HD causes motor, cognitive, and behavioral dysfunction. Since no existing treatment affects the course of this disease, new treatments are needed. Inflammation is frequently observed in HD patients before symptom onset. Neuroinflammation, characterized by the presence of reactive microglia and astrocytes and inflammatory factors within the brain, is also detected early. However, in comparison with other neurodegenerative diseases, the role of neuroinflammation in HD is much less known. Work has been dedicated to altered microglial and astrocytic functions in the context of HD, but less attention has been given to glial participation in neuroinflammation. This review describes evidence of inflammation in HD patients and animal models. It also discusses recent knowledge on neuroinflammation in HD, highlighting astrocyte and microglia involvement in the disease and considering anti-inflammatory therapeutic approaches.

scholarly journals New perspectives on the treatment of skeletal dysplasia

2020 ◽  
Vol 11 ◽  
pp. 204201882090401 ◽  
Author(s):  
Pauline Marzin ◽  
Valérie Cormier-Daire
Keyword(s):  
Skeletal Dysplasia ◽  
Multidisciplinary Approach ◽  
Cellular Therapy ◽  
Genetic Disorders ◽  
Pharmacological Therapy ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Morquio A ◽  
Underlying Pathophysiology

The last few decades have been marked by the identification of numerous genes implicated in genetic disorders, helping in the elucidation of the underlying pathophysiology of these conditions. This has allowed new therapeutic approaches to emerge such as cellular therapy, gene therapy, or pharmacological therapy for various conditions. Skeletal dysplasias are good models to illustrate these scientific advances. Indeed, several therapeutic strategies are currently being investigated in osteogenesis imperfecta; there are ongoing clinical trials based on pharmacological approaches, targeting signaling pathways in achondroplasia and fibrodysplasia ossificans progressiva or the endoplasmic reticulum stress in metaphyseal dysplasia type Schmid or pseudoachondroplasia. Moreover, the treatment of hypophosphatasia or Morquio A disease illustrates the efficacy of enzyme drug replacement. To provide a highly specialized multidisciplinary approach, these treatments are managed by reference centers. The emergence of treatments in skeletal dysplasia provides new perspectives on the prognosis of these severe conditions and may change prenatal counseling in these diseases over the coming years.

scholarly journals Limb specific Acvr1‐knockout during embryogenesis in mice exhibits great toe malformation as seen in Fibrodysplasia Ossificans Progressiva (FOP)

2019 ◽  
Vol 248 (5) ◽  
pp. 396-403 ◽  
Author(s):  
Laura Hildebrand ◽  
Mareen Schmidt‐von Kegler ◽  
Maria Walther ◽  
Petra Seemann ◽  
Katja Stange
Keyword(s):  
Fibrodysplasia Ossificans Progressiva ◽  
Great Toe

scholarly journals Mutant Activin-Like Kinase 2 in Fibrodysplasia Ossificans Progressiva are Activated via T203 by BMP Type II Receptors

2015 ◽  
Vol 29 (1) ◽  
pp. 140-152 ◽  
Author(s):  
Mai Fujimoto ◽  
Satoshi Ohte ◽  
Kenji Osawa ◽  
Arei Miyamoto ◽  
Sho Tsukamoto ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Soft Tissues ◽  
Genetic Disorder ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Type I ◽  
Type Ii ◽  
Activin Receptor ◽  
Bmp Receptors

Abstract Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder characterized by progressive heterotopic ossification in soft tissues, such as the skeletal muscles. FOP has been shown to be caused by gain-of-function mutations in activin receptor-like kinase (ALK)-2, which is a type I receptor for bone morphogenetic proteins (BMPs). In the present study, we examined the molecular mechanisms that underlie the activation of intracellular signaling by mutant ALK2. Mutant ALK2 from FOP patients enhanced the activation of intracellular signaling by type II BMP receptors, such as BMPR-II and activin receptor, type II B, whereas that from heart disease patients did not. This enhancement was dependent on the kinase activity of the type II receptors. Substitution mutations at all nine serine and threonine residues in the ALK2 glycine- and serine-rich domain simultaneously inhibited this enhancement by the type II receptors. Of the nine serine and threonine residues in ALK2, T203 was found to be critical for the enhancement by type II receptors. The T203 residue was conserved in all of the BMP type I receptors, and these residues were essential for intracellular signal transduction in response to ligand stimulation. The phosphorylation levels of the mutant ALK2 related to FOP were higher than those of wild-type ALK2 and were further increased by the presence of type II receptors. The phosphorylation levels of ALK2 were greatly reduced in mutants carrying a mutation at T203, even in the presence of type II receptors. These findings suggest that the mutant ALK2 related to FOP is enhanced by BMP type II receptors via the T203-regulated phosphorylation of ALK2.

Neurosurgical management of symptomatic thoracic spinal ossification in a patient with fibrodysplasia ossificans progressiva

2012 ◽  
Vol 16 (3) ◽  
pp. 285-288 ◽  
Author(s):  
Bartosz T. Grobelny ◽  
David Rubin ◽  
Peter Fleischut ◽  
Elayna Rubens ◽  
Patricia Fogarty Mack ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Genetic Disorder ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Anesthetic Technique ◽  
Minor Trauma ◽  
Thoracic Insufficiency Syndrome ◽  
Canal Stenosis ◽  
Thoracic Spinal ◽  
Muscle Tissues ◽  
Insufficiency Syndrome

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by heterotopic ossification of soft connective and muscle tissues, often as the result of minor trauma. The sequelae include joint fusion, accumulation of calcified foci within soft tissues, thoracic insufficiency syndrome, and progressive immobility. The authors report on a patient with FOP who developed severe spinal canal stenosis in the thoracic spine causing substantial myelopathy. He underwent a thoracic laminectomy and resection of a large posterior osteophyte. Unique considerations are required in treating patients with FOP, including steroid administration to prevent ossification and anesthetic technique. The nuances of neurosurgical and medical management as they pertain to this disease are discussed.

Sign in / Sign up

Export Citation Format

Share Document