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Japanese Journal of Radiology Mar 2022Skeletal dysplasia encompasses a heterogeneous group of over 400 genetic disorders. They are individually rare, but collectively rather common with an approximate... (Review)
Review
Skeletal dysplasia encompasses a heterogeneous group of over 400 genetic disorders. They are individually rare, but collectively rather common with an approximate incidence of 1/5000. Thus, radiologists occasionally encounter skeletal dysplasias in their daily practices, and the topic is commonly brought up in radiology board examinations across the world. However, many radiologists and trainees struggle with this issue because of the lack of proper resources. The radiological diagnosis of skeletal dysplasias primarily rests on pattern recognition-a method that is often called the "Aunt Minnie" approach. Most skeletal dysplasias have an identifiable pattern of skeletal changes composed of unique findings and even pathognomonic findings. Thus, skeletal dysplasias are the best example to which the Aunt Minnie approach is readily applicable.
Topics: Humans; Osteochondrodysplasias; Radiography
PubMed: 34693503
DOI: 10.1007/s11604-021-01206-5 -
Advances in Therapy May 2020Metabolic skeletal dysplasias comprise an extensive group of diseases capable of causing changes, usually progressive, in the bone and are due to hereditary disorders in...
Metabolic skeletal dysplasias comprise an extensive group of diseases capable of causing changes, usually progressive, in the bone and are due to hereditary disorders in many cases. The diagnosis and treatment of these diseases are not without difficulty, both because of their rarity and their possible confusion with more common diseases. A paradigmatic case of these metabolic skeletal dysplasias is X-linked hypophosphataemic rickets, which causes phosphaturia, a condition that alters the phosphate-calcium metabolism balance consequently causing, among other conditions, skeletal deformities and short stature. The genetic advances in recent years allow a much more accurate diagnosis of this disease when suspected, making differential diagnosis easier with similar entities but whose real causes are different. A better understanding of the phosphate-calcium metabolism allows us to replace the symptomatic treatment currently available with one that involves rebalancing the excess of fibroblast growth factor 23 (FGF23) by using monoclonal antibodies. In November 2018, a symposium sponsored by Kyowa Kirin Pharmaceuticals took place in Madrid, in which national and international experts addressed several aspects of these rare kidney diseases. Some topics addressed were the present and future genetic diagnosis, the use of multi-gene panels in renal or skeletal diseases, the role of animal models to better understand underlying skeletal changes, and the role of conventional radiology and surgery in the diagnosis and final treatment of bone deformities; all these without forgetting the important role of FGF23 and Klotho imbalances that result in the genetic change causing this disease. The optimization and limitations of conventional treatments currently available was also a topic addressed extensively, as well as the implications that new treatments against FGF23 could have in the future. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by the author.
Topics: Biomarkers; Bone Diseases, Metabolic; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Genetic Predisposition to Disease; Glucuronidase; Humans; Hypophosphatemia; Klotho Proteins; Male
PubMed: 32236867
DOI: 10.1007/s12325-019-01177-0 -
Developmental Dynamics : An Official... Apr 2022Primary cilia are dynamic compartments that regulate multiple aspects of cellular signaling. The production, maintenance, and function of cilia involve more than 1000... (Review)
Review
Primary cilia are dynamic compartments that regulate multiple aspects of cellular signaling. The production, maintenance, and function of cilia involve more than 1000 genes in mammals, and their mutations disrupt the ciliary signaling which manifests in a plethora of pathological conditions-the ciliopathies. Skeletal ciliopathies are genetic disorders affecting the development and homeostasis of the skeleton, and encompass a broad spectrum of pathologies ranging from isolated polydactyly to lethal syndromic dysplasias. The recent advances in forward genetics allowed for the identification of novel regulators of skeletogenesis, and revealed a growing list of ciliary proteins that are critical for signaling pathways implicated in bone physiology. Among these, a group of protein kinases involved in cilia assembly, maintenance, signaling, and disassembly has emerged. In this review, we summarize the functions of cilia kinases in skeletal development and disease, and discuss the available and upcoming treatment options.
Topics: Animals; Cilia; Ciliopathies; Homeostasis; Mammals; Polydactyly; Proteins
PubMed: 34582081
DOI: 10.1002/dvdy.426 -
Respiratory Medicine Oct 2017Skeletal dysplasia encompasses a variety of developmental disorders of the bone and cartilage that manifest as disproportionate shortening of limbs and trunk in the... (Review)
Review
BACKGROUND
Skeletal dysplasia encompasses a variety of developmental disorders of the bone and cartilage that manifest as disproportionate shortening of limbs and trunk in the neonate. Many types of skeletal dysplasia are complicated by respiratory failure at or soon after birth and require intensive care and prolonged hospitalization. Respiratory complications in these infants are complex and are characterized by airway anomalies, restrictive lung disease due to a narrow and abnormally compliant chest wall, pulmonary hypoplasia, and central apnea. Appropriate management of these unique patients requires a clear understanding of the pathophysiology and use of pulmonary function tests for early recognition and management of complications.
CONCLUSION
This review provides an overview of the underlying respiratory pathology and a practical guide to the newborn care provider for the diagnosis and management of respiratory complications in infants with skeletal dysplasia.
Topics: Bone Diseases, Developmental; Disease Management; Humans; Infant; Infant, Newborn; Lung; Lung Diseases; Respiratory Function Tests; Respiratory Insufficiency; Sleep Apnea, Central; Thoracic Wall
PubMed: 28947027
DOI: 10.1016/j.rmed.2017.07.063 -
Bone Nov 2020Small regulatory microRNAs (miRNAs) post-transcriptionally suppress gene expression. MiRNAs expressed in skeletal progenitor cells and chondrocytes regulate diverse... (Review)
Review
Small regulatory microRNAs (miRNAs) post-transcriptionally suppress gene expression. MiRNAs expressed in skeletal progenitor cells and chondrocytes regulate diverse aspects of cellular function and thus skeletal development. In this review, we discuss the role of miRNAs in skeletal development, particularly focusing on those whose physiological roles were revealed in vivo. Deregulation of miRNAs is found in multiple acquired diseases such as cancer; however congenital diseases caused by mutations in miRNA genes are very rare. Among those are mutations in miR-140 and miR-17~92 miRNAs which cause skeletal dysplasias. We also discuss pathological mechanisms underlining these skeletal dysplasias.
Topics: Animals; Bone Diseases; Cartilage; Chondrocytes; Humans; MicroRNAs; Stem Cells
PubMed: 32745689
DOI: 10.1016/j.bone.2020.115564 -
Frontiers in Genetics 2021In 2019, the Nosology Committee of the International Skeletal Dysplasia Society provided an updated version of the Nosology and Classification of Genetic Skeletal... (Review)
Review
In 2019, the Nosology Committee of the International Skeletal Dysplasia Society provided an updated version of the Nosology and Classification of Genetic Skeletal Disorders. This is a reference list of recognized diseases in humans and their causal genes published to help clinician diagnosis and scientific research advances. Complementary to mammalian models, zebrafish has emerged as an interesting species to evaluate chemical treatments against these human skeletal disorders. Due to its versatility and the low cost of experiments, more than 80 models are currently available. In this article, we review the state-of-art of this "aquarium to bedside" approach describing the models according to the list provided by the Nosology Committee. With this, we intend to stimulate research in the appropriate direction to efficiently meet the actual needs of clinicians under the scope of the Nosology Committee.
PubMed: 34490030
DOI: 10.3389/fgene.2021.675331 -
Annual Review of Genomics and Human... Aug 2023The transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways play a pivotal role in bone development and skeletal health. More than... (Review)
Review
The transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways play a pivotal role in bone development and skeletal health. More than 30 different types of skeletal dysplasia are now known to be caused by pathogenic variants in genes that belong to the TGF-β superfamily and/or regulate TGF-β/BMP bioavailability. This review describes the latest advances in skeletal dysplasia that is due to impaired TGF-β/BMP signaling and results in short stature (acromelic dysplasia and cardiospondylocarpofacial syndrome) or tall stature (Marfan syndrome). We thoroughly describe the clinical features of the patients, the underlying genetic findings, and the pathomolecular mechanisms leading to disease, which have been investigated mainly using patient-derived skin fibroblasts and mouse models. Although no pharmacological treatment is yet available for skeletal dysplasia due to impaired TGF-β/BMP signaling, in recent years advances in the use of drugs targeting TGF-β have been made, and we also discuss these advances.
Topics: Animals; Mice; Osteochondrodysplasias; Osteosclerosis; Biological Availability; Bone Development; Transforming Growth Factor beta
PubMed: 37624666
DOI: 10.1146/annurev-genom-120922-094107 -
Annual Review of Genomics and Human... 2015Skeletal dysplasias result from disruptions in normal skeletal growth and development and are a major contributor to severe short stature. They occur in approximately... (Review)
Review
Skeletal dysplasias result from disruptions in normal skeletal growth and development and are a major contributor to severe short stature. They occur in approximately 1/5,000 births, and some are lethal. Since the most recent publication of the Nosology and Classification of Genetic Skeletal Disorders, genetic causes of 56 skeletal disorders have been uncovered. This remarkable rate of discovery is largely due to the expanded use of high-throughput genomic technologies. In this review, we discuss these recent discoveries and our understanding of the molecular mechanisms behind these skeletal dysplasia phenotypes. We also cover potential therapies, unusual genetic mechanisms, and novel skeletal syndromes both with and without known genetic causes. The acceleration of skeletal dysplasia genetics is truly spectacular, and these advances hold great promise for diagnostics, risk prediction, and therapeutic design.
Topics: Animals; Body Height; Bone Diseases, Developmental; Disease Models, Animal; Dwarfism; Epigenesis, Genetic; High-Throughput Nucleotide Sequencing; Histone Acetyltransferases; Humans; Mice; MicroRNAs; Mutation; Osteochondrodysplasias; Proteus Syndrome
PubMed: 25939055
DOI: 10.1146/annurev-genom-090314-045904 -
Diagnostics (Basel, Switzerland) Sep 2023This paper presents a rare case of fetal hydrops detected at just 23 weeks of gestation in a 22-year-old woman's first pregnancy. The fetal ultrasound revealed severe...
This paper presents a rare case of fetal hydrops detected at just 23 weeks of gestation in a 22-year-old woman's first pregnancy. The fetal ultrasound revealed severe skeletal anomalies, craniofacial deformities, and thoracic abnormalities, suggesting a complex and severe skeletal dysplasia, potentially type IA Achondrogenesis-a lethal autosomal recessive condition marked by ossification delay. This case highlights the significance of advanced genetic testing, such as next-generation sequencing (NGS) and whole-genome sequencing (WGS), in diagnosing and understanding skeletal dysplasias. Skeletal dysplasias represent a group of genetic disorders that affect osteogenesis. The prevalence of this condition is 1 in 4000 births. Sadly, 25% of affected infants are stillborn, and around 30% do not survive the neonatal period. There is a wide range of rare skeletal dysplasias, each with its own specific recurrence risk, dysmorphic expression, and implications for neonatal survival and quality of life. When skeletal dysplasia is incidentally discovered during routine ultrasound screening in a pregnancy not known to be at risk of a specific syndrome, a systematic examination of the limbs, head, thorax, and spine is necessary to reach the correct diagnosis. Prenatal diagnosis of skeletal dysplasia is crucial for providing accurate counselling to future parents and facilitating the proper management of affected pregnancies. An accurate diagnosis can be a real challenge due to the wide spectrum of clinical presentations of skeletal dysplasia but advances in imaging technologies and molecular genetics have improved accuracy. Additionally, some of these skeletal dysplasias may present clinical overlap, making it especially difficult to distinguish. After the 11th revision of genetic skeletal disorder nosology, there are 771 entities associated with 552 gene mutations. The most common types of skeletal dysplasia are thanatophoric dysplasia, osteogenesis imperfect, achondroplasia, achondrogenesis, and asphyxiating thoracic dystrophy.
PubMed: 37761271
DOI: 10.3390/diagnostics13182905