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American Journal of Medical Genetics.... Oct 2016Quantum advances have occurred in the field of human genetics in the six decades since Watson and Crick expressed their "wish to suggest a structure for the salt of... (Review)
Review
Quantum advances have occurred in the field of human genetics in the six decades since Watson and Crick expressed their "wish to suggest a structure for the salt of deoxyribose nucleic acid." These culminated with the human genome project, which has opened up myriad possibilities, including that of individualized genetic medicine, the ability to deliver medical advice, management, and therapy tailored to an individual's genetic blueprint. Advances in genetic diagnostic capabilities have been rapid, to the point where the genome can be sequenced for several thousand dollars. Crucially, it has facilitated the identification of targets for "precision" treatments to combat genetic diseases at their source. This manuscript will review the innovative, pathogenesis-based therapies that are revolutionizing management of skeletal dysplasias, giving patients and families new options and outcomes. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Combined Modality Therapy; Genetic Association Studies; Humans; Molecular Targeted Therapy; Mutation; Osteochondrodysplasias; Signal Transduction; Treatment Outcome
PubMed: 27155200
DOI: 10.1002/ajmg.a.37734 -
Modern Pathology : An Official Journal... Jan 2017Upper aerodigestive tract (UADT) mucosal premalignant lesions include non-keratinizing and keratinizing intraepithelial dysplasia. The keratinizing type of... (Review)
Review
Upper aerodigestive tract (UADT) mucosal premalignant lesions include non-keratinizing and keratinizing intraepithelial dysplasia. The keratinizing type of intraepithelial dysplasia represents the majority of UADT dysplasias. Historically, grading of UADT dysplasias has followed a three tier system to include mild, moderate and severe dysplasia. Recent recommendations have introduced a two tier grading scheme to including low-grade (ie, mild dysplasia) and high-grade (moderate and severe dysplasia/carcinoma in situ) providing for better consensus among pathologists in the interpretation of such dysplastic lesions. Squamous cell carcinoma is the most common malignant neoplasm of the UADT. Several variants of squamous cell carcinoma are recognized among which the more common types include papillary squamous cell carcinoma, verrucous carcinoma, spindle cell squamous cell carcinoma (sarcomatoid carcinoma) and basaloid squamous cell carcinoma. Each of these variants of squamous cell carcinoma poses diagnostic challenges and each correlates to specific therapy and prognosis. This review details the proposed update in the grading of UADT dysplasia to a two-tiered system as well as providing the key diagnostic features for select variants of squamous cell carcinoma.
Topics: Carcinoma, Squamous Cell; Humans; Hyperplasia; Oropharyngeal Neoplasms; Precancerous Conditions
PubMed: 28060368
DOI: 10.1038/modpathol.2016.207 -
Clinical Endoscopy Sep 2017Long-standing intestinal inflammation in patients with inflammatory bowel disease (IBD) induces dysplastic change in the intestinal mucosa and increases the risk of... (Review)
Review
Long-standing intestinal inflammation in patients with inflammatory bowel disease (IBD) induces dysplastic change in the intestinal mucosa and increases the risk of subsequent colorectal cancer. The evolving endoscopic techniques and technologies, including dye spraying methods and high-definition images, have been replacing random biopsies and have been revealed as more practical and efficient for detection of dysplasia in IBD patients. In addition, they have potential usefulness in detailed characterization of lesions and in the assessment of endoscopic resectability. Most dysplastic lesions without an unclear margin, definite ulceration, non-lifting sign, and high index of malignant change with suspicion for lymph node or distant metastases can be removed endoscopically. However, endoscopic resection of dysplasia in chronic IBD patients is usually difficult because it is often complicated by submucosal fibrosis. In patients with dysplasias that demonstrate submucosa fibrosis or a large size (≥20 mm), endoscopic submucosal dissection (ESD) or ESD with snaring (simplified or hybrid ESD) is an alternative option and may avoid a colectomy. However, a standardized endoscopic therapeutic approach for dysplasia in IBD has not been established yet, and dedicated specialized endoscopists with interest in IBD are needed to fully investigate recent emerging techniques and technologies.
PubMed: 29017293
DOI: 10.5946/ce.2017.132 -
Ceskoslovenska Patologie 2018Columnar lined esophagus is a complication of long term gastroesophageal reflux disease and the main precursor of esophageal adenocarcinoma. Incomplete intestinal...
Columnar lined esophagus is a complication of long term gastroesophageal reflux disease and the main precursor of esophageal adenocarcinoma. Incomplete intestinal metaplasia in reflux esophagitis represents one of the most important risk factors for neoplastic transformation through the metaplasia-dysplasia-adenocarcinoma sequence. However, recent studies suggest that cardiac type mucosa also shows molecular abnormalities which are similar to those of incomplete intestinal metaplasia. Immunohistochemically, three types of esophageal dysplasia and adenocarcinoma are recognized: adenomatous-intestinal, hybrid/mixed and foveolar gastric types. We are interested in the phenotypes of these dysplasias and adenocarcinomas, especially in the possible relationship between them. For this reason, we evaluated the immunohistochemical expression of intestinal and gastric markers in a series of 30 cases of esophageal high-grade dysplasia (high-grade intraepithelial neoplasia) and of 70 adenocarcinomas. For immunohistochemical classification, we used double immunohistochemical reactions CDX2/MUC5AC and CDX2/MUC6, respectively. In cases of incomplete intestinal metaplasia, hybrid/mixed high-grade dysplasia and hybrid/mixed adenocarcinoma, we found the expression of gastric mucins MUC5AC and MUC6 only in cells with intestinal differentiation (with nuclear positivity for CDX2). The double immunostaining excluded the presence of the cells with "pure" foveolar gastric phenotype in hybrid lesions. Thus, the hybrid category actually represents the intestinal type dysplasia/adenocarcinoma (which is known to have a better prognosis than the foveolar gastric type). Keywords: immunohistochemistry - double immunostaining - reflux esophagitis - Barrett esophagus - esophageal dysplasia - esophageal adenocarcinoma.
Topics: Adenocarcinoma; Barrett Esophagus; Esophageal Neoplasms; Humans; Immunohistochemistry; Metaplasia; Precancerous Conditions; Stomach
PubMed: 30441967
DOI: No ID Found -
American Journal of Medical Genetics.... Oct 2014The ectodermal dysplasias (EDs) are a heterogeneous group of disorders characterized by a deficiency of ectoderm- and mesoderm-derived tissues and appendages,... (Review)
Review
The ectodermal dysplasias (EDs) are a heterogeneous group of disorders characterized by a deficiency of ectoderm- and mesoderm-derived tissues and appendages, particularly hair, skin, teeth, and nails. Many of these disorders are associated with a greater risk of respiratory disease than found in the general population. There are no published papers that comprehensively describe these findings and the possible etiologies. Patients have been reported with dramatic decrease in mucous glands in the respiratory tract. Anatomic defects, including cleft palate, that predispose to respiratory infection, are associated with several of the ED syndromes. Atopy and immune deficiencies have been shown to have a higher prevalence in ED syndromes. Clinicians who care for patients affected by ED syndromes should be aware of the potential respiratory complications, and consider evaluation for structural anomalies, atopy and immunodeficiency in individuals with recurrent or chronic respiratory symptoms.
Topics: Cleft Palate; Ectodermal Dysplasia; Humans; Immunologic Deficiency Syndromes; Respiratory Mucosa; Respiratory System; Respiratory Tract Diseases
PubMed: 24842607
DOI: 10.1002/ajmg.a.36600 -
Seminars in Musculoskeletal Radiology Feb 2018Skeletal dysplasia is a heterogeneous group of abnormalities affecting growth and development of bone and cartilage characterized by disproportionate shortening of the... (Review)
Review
Skeletal dysplasia is a heterogeneous group of abnormalities affecting growth and development of bone and cartilage characterized by disproportionate shortening of the limbs and/or spine. A systematic radiographic approach combined with pertinent clinical details can help guide specific genetic testing and treatment. We provide a discussion and examples of a few common and notable skeletal dysplasias to help familiarize general, pediatric, and musculoskeletal radiologists who do not commonly encounter children with these entities in their daily practices.
Topics: Child; Diagnosis, Differential; Humans; Musculoskeletal Abnormalities; Osteochondrodysplasias
PubMed: 29409074
DOI: 10.1055/s-0037-1608005 -
Balkan Journal of Medical Genetics :... May 2023Diastrophic dysplasia (DTD) is an uncommon pathology which falls under the group of skeletal dysplasias with its first symptoms observed from birth. The pathology is...
Diastrophic dysplasia (DTD) is an uncommon pathology which falls under the group of skeletal dysplasias with its first symptoms observed from birth. The pathology is often featured by short stature and abnormally short extremities (also known as short-limbed dwarfism); the osseous structures of the body (bones and joints) are characterized through defective development in many body regions. More than 300 genes were reported to be involved in DTD etiology with autosomal recessive, autosomal dominant and X-linked manner. We describe clinical case of a 42-year-old woman from the west of Ukraine with diastrophic dysplasia and two pathogenic variants and identified in gene. SLC26A2-related diastrophic dysplasia was confirmed based on the presence of pathogenic variants in , which is associated with autosomal recessive forms of skeletal dysplasia, combined with phenotypic symptoms and radiographic findings.
PubMed: 37265969
DOI: 10.2478/bjmg-2022-0018 -
American Journal of Medical Genetics.... Oct 2014Ectodermal dysplasias are a large group of heterogeneous heritable conditions characterized by congenital defects of one or more ectodermal structures and their... (Review)
Review
Ectodermal dysplasias are a large group of heterogeneous heritable conditions characterized by congenital defects of one or more ectodermal structures and their appendages. The skin and its appendages are mainly composed by ectodermal components but development initiation of appendages is orchestrated by signals of the mesoderm with the help of placodes. A complex network of signaling pathways coordinates the formation and function of ectodermal structures. In recent years much has been discovered regarding the molecular mechanisms of ectodermal embryogenesis and this facilitates a rational basis for classification of ectodermal dysplasia. Interestingly, not only complex ectodermal syndromes but also mono- or oligosymptomatic ectodermal malformations may result from a mutation in a gene that is critical for ectodermal development. Mesodermal, and occasionally endodermal malformations may coexist. Embryogenesis occurs in distinct tissue organizational fields and specific interactions among the germ layers exist that may lead to a wide range of ectodermal dysplasias. Of the approximately 200 different ectodermal dysplasias, about 80 have been characterized at the molecular level with identification of the genes that are mutated in these disorders. Modern molecular genetics will increasingly elucidate the basic defects of these distinct syndromes and shed more light into the regulatory mechanisms of embryology. The upcoming classification of ectodermal dysplasias will combine detailed clinical and molecular knowledge.
Topics: Animals; Ectodermal Dysplasia; Embryonic Development; Humans; Mutation; Skin
PubMed: 24715647
DOI: 10.1002/ajmg.a.36550 -
Journal of Postgraduate Medicine 2018We aimed to review the contributions by Indian researchers to the subspecialty of skeletal dysplasias (SDs). Literature search using specific keywords in PubMed was... (Review)
Review
We aimed to review the contributions by Indian researchers to the subspecialty of skeletal dysplasias (SDs). Literature search using specific keywords in PubMed was performed to retrieve all the published literature on SDs as on July 6, 2017. All published literature on SDs wherein at least one author was from an Indian institute was included. Publications were grouped into different categories based on the major emphasis of the research paper. Five hundred and forty publications in English language were retrieved and categorized into five different groups. The publications were categorized as reports based on: (i) phenotypes (n = 437), (ii) mutations (n = 51), (iii) novel genes (n = 9), (iv) therapeutic interventions (n = 31), and (v) reviews (n = 12). Most of the publications were single-patient case reports describing the clinical and radiological features of the patients affected with SDs (n = 352). We enlisted all the significant Indian contributions. We have also highlighted the reports in which Indians have contributed to discovery of new genes and phenotypes. This review highlights the substantial Indian contributions to SD research, which is poised to reach even greater heights given the size and structure of our population, technological advances, and expanding national and international collaborations.
Topics: Bibliometrics; Biomedical Research; Humans; India; Osteochondrodysplasias; Publishing
PubMed: 29692401
DOI: 10.4103/jpgm.JPGM_527_17 -
Orthopaedics & Traumatology, Surgery &... Feb 2022Trochlear dysplasia consists in deficient trochlear concavity, giving rise to a flat or convex trochlea, and is the main risk factor for patellar dislocation. Surgical... (Review)
Review
Trochlear dysplasia consists in deficient trochlear concavity, giving rise to a flat or convex trochlea, and is the main risk factor for patellar dislocation. Surgical indications depend on familiarity with trochlear dysplasias, and especially those of high grade, identified on clinical examination and standard and cross-sectional imaging, and on quantification of associated instability factors. Treatment strategy is accordingly determined "à la carte" to correct these factors one by one. Sulcus deepening trochleoplasty corrects the morphology and is the appropriate etiological treatment. It gives good results in terms of recurrence of dislocation, but tends to cause knee stiffness and patellofemoral osteoarthritis. Indications are based on objective patellar instability associated to high-grade B or D dysplasia. Medial patellofemoral ligament reconstruction should be systematically associated. The lateral retinaculum is systematically sectioned, as patellar tilt is never reducible in such high-grade dysplasia. Trochleoplasty corrects the sulcus defect, resolves protrusion and enables proximal realignment. The main complications are stiffness and pain due to persistence or onset of cartilage lesions. Trochleoplasty is indicated: 1) in first line for objective patellar instability associated with high-grade dysplasia; or 2) for recurrence in high-grade dysplasia previously managed by other surgery. The aim of the present study was to review the literature on trochleoplasty and address the following questions: how to define high-grade dysplasia? What are the key clinical and radiologic points? What are the risk factors for patellar dislocation? What trochleoplasty techniques are available? What results can be expected? Level of evidence: V; expert opinion.
Topics: Femur; Humans; Joint Instability; Ligaments, Articular; Patellar Dislocation; Patellofemoral Joint
PubMed: 34863959
DOI: 10.1016/j.otsr.2021.103160