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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 -
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 -
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 -
Indian Journal of Pathology &... May 2022Focal cortical dysplasias (FCDs) represent the third most frequent cause of drug-resistant focal epilepsy in adults (after hippocampal sclerosis and tumours) submitted... (Review)
Review
Focal cortical dysplasias (FCDs) represent the third most frequent cause of drug-resistant focal epilepsy in adults (after hippocampal sclerosis and tumours) submitted to surgery, and the most common in the pediatric age group. The International League Against Epilepsy (ILAE) classification of focal cortical dysplasia is still a reference and consists of a three-tiered system: FCD type I refers to isolated abnormalities in cortical layering; FCD type II refers to cases with abnormalities in cortical architecture and dysmorphic neurons with or without balloon cells; and FCD type III refers to abnormalities in cortical layering associated with other lesions. Recent studies have demonstrated that somatic mutations occurring post-zygotically during embryonal development and leading to mosaicism, underlie most brain malformations. The molecular pathogenesis of FCD type II is associated with activation of the mTOR pathway. Pathogenic variants in this pathway are recognized in up to 63% of cases and may occur both through single activating variants in activators of the mTOR signaling pathway or double-hit inactivating variants in repressors of the signaling pathway. The newly described mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy, has been found to show recurrent pathogenic variants in SLC35A2 with mosaicism. The present review describes the lesions of FCD and discusses the molecular pathogenesis and proposal for a revised classification.
Topics: Adult; Child; Epilepsy; Humans; Malformations of Cortical Development; Mosaicism; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 35562149
DOI: 10.4103/ijpm.ijpm_1226_21