-
Neuroimaging Clinics of North America Feb 2019Many bone dysplasias, some common and others rare, may involve the temporal bone causing conductive, sensorineural, or mixed hearing loss, vestibular dysfunction, or... (Review)
Review
Many bone dysplasias, some common and others rare, may involve the temporal bone causing conductive, sensorineural, or mixed hearing loss, vestibular dysfunction, or skull base foraminal narrowing, potentially affecting quality of life. Some conditions may affect only the temporal bone, whereas others may be more generalized, involving different regions of the body. High-resolution computed tomography may detect subtle osseous changes that can help define the type of dysplasia, and MR imaging can help define the degree of activity of lesions and potential associated complications.
Topics: Bone Diseases, Developmental; Humans; Magnetic Resonance Imaging; Otosclerosis; Temporal Bone; Tomography, X-Ray Computed
PubMed: 30466643
DOI: 10.1016/j.nic.2018.09.004 -
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 -
Ceskoslovenska Patologie 2023We present a comprehensive review dealing with rare genetic skeletal disorders. More than 400 entities are included in the latest classification. The most severe or... (Review)
Review
We present a comprehensive review dealing with rare genetic skeletal disorders. More than 400 entities are included in the latest classification. The most severe or lethal phenotypes are identifiable in the prenatal period and the pregnancy can be terminated. Perinatal autopsy and posmortem X-rays are crucial in providing a definitive diagnosis. The number of cases confirmed by genetic testing is increasing. We report our own experience with genetic skeletal disorders based on 41 illustrative fetal and neonatal cases which we encountered over a 10-year period. Thanatophoric dysplasia and osteogenesis imperfecta represent approximately half of the cases coming to autopsy. Achondrogenesis type 2 and hypochondrogenesis, short-rib dysplasia, chondrodysplasia punctata, campomelic dysplasia and achondroplasia are less common. Skeletal dysplasias with autosomal recessive inheritance are the least frequent, e.g. perinatally lethal hypophophatasia, achondrogenesis type 1A, diastrophic dysplasia/atelosteogenesis type 2 or mucolipidosis type 2 (I cell disease).
Topics: Pregnancy; Female; Humans; Osteochondrodysplasias; Thanatophoric Dysplasia; Campomelic Dysplasia; Receptor, Fibroblast Growth Factor, Type 3; Fetus
PubMed: 37468326
DOI: No ID Found -
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 -
Surgical Pathology Clinics Sep 2017The jaws combine several unique properties that mainly result from their distinct embryonic development and their role in providing anchorage for the teeth and their... (Review)
Review
The jaws combine several unique properties that mainly result from their distinct embryonic development and their role in providing anchorage for the teeth and their supporting structures. As a consequence, several bone-related lesions almost exclusively develop in the jaws (eg, osseous dysplasias, ossifying fibromas), have distinct clinical features (eg, osteosarcoma), or hardly ever occur at this location (eg, osteochondroma, enchondroma). The specific characteristics of these tumors and tumorlike lesions are outlined in this article.
Topics: Bone Cysts, Aneurysmal; Cherubism; Fibroma, Ossifying; Fibrous Dysplasia of Bone; Granuloma, Giant Cell; Humans; Jaw Diseases; Jaw Neoplasms; Osteosarcoma
PubMed: 28797509
DOI: 10.1016/j.path.2017.04.007 -
Matrix Biology : Journal of the... Jul 2019The fibrillins are large extracellular matrix molecules that polymerize to form microfibrils. Fibrillin microfibrils are distinctive architectural elements that are both... (Review)
Review
The fibrillins are large extracellular matrix molecules that polymerize to form microfibrils. Fibrillin microfibrils are distinctive architectural elements that are both ubiquitous in the connective tissue space and also unique, displaying tissue-specific patterns. Mutations in the genes for fibrillin-1 (FBN1) result in multiple distinct pleiotropic disorders. Most of the more than 3000 mutations known today in FBN1 cause the Marfan syndrome. Marfan mutations can occur in any of the 56 domains that compose fibrillin-1. In contrast, rare mutations in FBN1 that are confined to only certain domains cause several different types of acromelic dysplasia. These genetic disorders demonstrate that specific domains of fibrillin-1 perform roles important to musculoskeletal growth. Many of the phenotypes of acromelic dysplasias are the opposite of those found in Marfan syndrome. Knowledge of the functions and structural organization of fibrillin molecules within microfibrils is required to understand how one protein and one gene can be the basis for multiple genetic disorders.
Topics: Bone Diseases, Developmental; Contracture; Fibrillin-1; Genetic Predisposition to Disease; Humans; Limb Deformities, Congenital; Musculoskeletal Development; Mutation; Protein Domains; Skin Diseases, Genetic
PubMed: 30219651
DOI: 10.1016/j.matbio.2018.09.005 -
Dermatologic Clinics Oct 2018Trichoscopy allows analyzing the structure and size of growing hair shafts in their natural environment in children and adults. The method replaces light microscopy,... (Review)
Review
Trichoscopy allows analyzing the structure and size of growing hair shafts in their natural environment in children and adults. The method replaces light microscopy, which requires pulling of multiple hairs for investigation. In monilethrix, trichoscopy shows uniform elliptical nodosities with intermittent constrictions. In trichorrhexis nodosa nodular thickenings along hairs shafts are visible (low magnification) or splitting into numerous small fibers along the hair shaft may be observed (high magnification). In trichorrhexis invaginata (bamboo hair) the hair shaft telescopes into itself at several points along the shaft. Trichoscopy shows small nodules along the shaft. Hairs bend and break in these diseases. Trichoscopy of pili torti shows twists of hair shafts along their long axis. In pili annulati hair shafts with alternating white and dark bands are visible. In woolly hair the examination demonstrates hair shafts with waves at very short intervals. For trichothiodystrophy polarized trichoscopy should be used. In ectodermal dysplasias, trichoscopy shows a variety of hair abnormalities, but the most characteristic finding is hair shaft pigmentation heterogeneity.
Topics: Dermoscopy; Ectodermal Dysplasia; Hair; Hair Diseases; Hair Follicle; Humans; Monilethrix; Netherton Syndrome; Trichothiodystrophy Syndromes
PubMed: 30201151
DOI: 10.1016/j.det.2018.05.009 -
Clinical Genetics Apr 2020Ectodermal dysplasias are a family of genodermatoses commonly associated with variants in the ectodysplasin/NF-κB or the Wnt/β-catenin pathways. Both pathways are...
Ectodermal dysplasias are a family of genodermatoses commonly associated with variants in the ectodysplasin/NF-κB or the Wnt/β-catenin pathways. Both pathways are involved in signal transduction from ectoderm to mesenchyme during the development of ectoderm-derived structures. Wnt/β-catenin pathway requires the lymphoid enhancer-binding factor 1 (LEF1), a nuclear mediator, to activate target gene expression. In mice, targeted inactivation of the LEF1 gene results in a complete block of development of multiple ectodermal appendages. We report two unrelated patients with 4q25 de novo deletion encompassing LEF1, associated with severe oligodontia of primary and permanent dentition, hypotrichosis and hypohidrosis compatible with hypohidrotic ectodermal dysplasia. Taurodontism and a particular alveolar bone defect were also observed in both patients. So far, no pathogenic variants or variations involving the LEF1 gene have been reported in human. We provide further evidence for LEF1 haploinsufficiency role in ectodermal dysplasia and delineate its clinical phenotype.
Topics: Adult; Animals; Child, Preschool; Ectodermal Dysplasia; Ectodermal Dysplasia 1, Anhidrotic; Female; Haploinsufficiency; Humans; Lymphoid Enhancer-Binding Factor 1; Male; Mice; NF-kappa B; Signal Transduction; Young Adult; beta Catenin
PubMed: 32022899
DOI: 10.1111/cge.13714 -
European Journal of Medical Genetics Apr 2016Acromesomelic dysplasia is a type of skeletal malformation affecting distal and middle segments of the extremities. It occurs in both isolated (non-syndromic) and... (Review)
Review
Acromesomelic dysplasia is a type of skeletal malformation affecting distal and middle segments of the extremities. It occurs in both isolated (non-syndromic) and syndromic forms. In later case, it shows association with cardiac, respiratory, neurological and genital abnormalities. Acromesomelic dysplasia segregates in autosomal recessive mode. Mutations in three genes (GDF5, NPR2, BMPR1B) have been reported to cause different forms of acromesomelic dysplasia. In the present review, we have discussed clinical spectrum, genetics and signalopathies of isolated acromesomelic dysplasias.
Topics: Bone Morphogenetic Protein Receptors, Type I; Consanguinity; Dwarfism; Growth Differentiation Factor 5; Humans; Musculoskeletal Abnormalities; Mutation; Osteochondrodysplasias; Pedigree; Phenotype; Receptors, Atrial Natriuretic Factor
PubMed: 26926249
DOI: 10.1016/j.ejmg.2016.02.011