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American Journal of Medical Genetics.... Dec 2015Fractures in infancy or early childhood require prompt evaluation with consideration of accidental or non-accidental trauma as well as a large number of genetic... (Review)
Review
Fractures in infancy or early childhood require prompt evaluation with consideration of accidental or non-accidental trauma as well as a large number of genetic disorders that predispose to fractures. Bone fragility has been reported in more than 100 genetic disorders, including skeletal dysplasias, inborn errors of metabolism and congenital insensitivity to pain. Most of these disorders are rare but often have distinctive clinical or radiographic findings to assist in the diagnosis. Gene sequencing is available, albeit connective tissue and skeletal dysplasia panels and biochemical studies are only helpful in a minority of cases. This article presents the clinical, radiographic, and molecular profiles of the most common heritable disorders other than osteogenesis imperfecta with increased bone fragility. In addition, the clinicians must consider non-heritable influences such as extreme prematurity, prenatal viral infection and neoplasia in the diagnostic process.
Topics: Bone Diseases, Developmental; Bone and Bones; Child; Child, Preschool; Diagnosis, Differential; Fractures, Bone; Humans; Infant; Musculoskeletal Abnormalities; Radiography
PubMed: 26531771
DOI: 10.1002/ajmg.c.31466 -
Annals of Pediatric Endocrinology &... Jun 2022Skeletal dysplasia is a diverse group of disorders that affect bone development and morphology. Currently, approximately 461 different genetic skeletal disorders have...
Skeletal dysplasia is a diverse group of disorders that affect bone development and morphology. Currently, approximately 461 different genetic skeletal disorders have been identified, with over 430 causative genes. Among these, fibroblast growth factor receptor 3 (FGFR3)-related skeletal dysplasia is a relatively common subgroup of skeletal dysplasia. Pediatric endocrinologists may encounter a suspected case of skeletal dysplasia in their practice, especially when evaluating children with short stature. Early and accurate diagnosis of FGFR3-related skeletal dysplasia is essential for timely management of complications and genetic counseling. This review summarizes 5 representative and distinct entities of skeletal dysplasia caused by pathogenic variants in FGFR3 and discusses emerging therapies for FGFR3-related skeletal dysplasias.
PubMed: 35793999
DOI: 10.6065/apem.2244114.057 -
Pediatric Radiology Nov 2020Skeletal dysplasias are a large group of rare conditions with widely heterogeneous manifestations and a reputation for being diagnostically difficult. Involvement of the... (Review)
Review
Skeletal dysplasias are a large group of rare conditions with widely heterogeneous manifestations and a reputation for being diagnostically difficult. Involvement of the brain and craniovertebral junction are features familiar to the paediatric neuroradiologist. Involvement of the skull itself represents an area of overlap between the domains of the neuroradiologist and the skeletal dysplasia radiologist. In this pictorial essay, we review the principal skull manifestations of skeletal dysplasias as they present to the neuroradiologist.
Topics: Adolescent; Bone Diseases, Developmental; Child; Child, Preschool; Diagnostic Imaging; Female; Humans; Infant; Male; Skull
PubMed: 33135136
DOI: 10.1007/s00247-019-04473-7 -
European Journal of Radiology Jun 2021Pulsatile tinnitus (PT) can be a mild or debilitating symptom. Following clinical examination and otoscopy, when the underlying aetiology is not apparent, radiological... (Review)
Review
Pulsatile tinnitus (PT) can be a mild or debilitating symptom. Following clinical examination and otoscopy, when the underlying aetiology is not apparent, radiological imaging can be used to evaluate further. CT arteriography-venography (CT A-V) of the head and neck has recently been introduced as a single 'one catch' modality for identifying the many causes of PT including those which are treatable and potentially serious whilst also providing reassurance through negative studies or studies with benign findings. CT A-V is performed as a single phase study allowing both arterial and venous assessment, hence limiting radiation exposure. Additional multiplanar reformats and bone reconstructions are desirable. Understanding the limitations of CT A-V is also required, with an awareness of the scenarios where other imaging modalities should be considered. The causes of PT can be divided into systemic and non-systemic categories. Non-systemic aetiologies in the head and neck should be carefully reviewed on CT A-V and include a variety of vascular causes (arteriovenous malformations/fistulas, venous or arterial aetiologies) and non-vascular causes (tumours and bony dysplasias). Venous causes (dominant, aberrant, stenosed or thrombosed venous vessels) are more common than arterial aetiologies (aberrant or stenosed internal carotid artery, aneurysms or a persistent stapedial artery). Glomus tumours that are not visible on otoscopy and osseous pathologies such as bony dehiscence and otospongiosis should also be excluded. Careful assessment of all the potential vascular and non-vascular causes should be reviewed in a systematic approach, with correlation made with the clinical history. A structured reporting template for the reporting radiologist is provided in this review to ensure all the potential causes of PT are considered on a CT A-V study. This will help in providing a comprehensive radiological evaluation, hence justifying the radiation dose and for patient assessment and prognostication.
Topics: Aneurysm; Angiography; Arteriovenous Fistula; Humans; Phlebography; Tinnitus
PubMed: 33894642
DOI: 10.1016/j.ejrad.2021.109722 -
Orphanet Journal of Rare Diseases Jun 2016The large chondroitin sulphated proteoglycan aggrecan (ACAN) is the most abundant non-collagenous protein in cartilage and is essential for its structure and function.... (Review)
Review
The large chondroitin sulphated proteoglycan aggrecan (ACAN) is the most abundant non-collagenous protein in cartilage and is essential for its structure and function. Mutations in ACAN result in a broad phenotypic spectrum of non-lethal skeletal dysplasias including spondyloepimetaphyseal dysplasia, spondyloepiphyseal dysplasia, familial osteochondritis dissecans and various undefined short stature syndromes associated with accelerated bone maturation. However, very little is currently known about the disease pathways that underlie these aggrecanopathies, although they are likely to be a combination of haploinsufficiency and dominant-negative (neomorphic) mechanisms. This review discusses the known human and animal aggrecanopathies in the context of clinical presentation and potential disease mechanisms.
Topics: Aggrecans; Bone Diseases, Developmental; Cartilage; Humans; Mutation; Osteochondrodysplasias; Pedigree
PubMed: 27353333
DOI: 10.1186/s13023-016-0459-2 -
Expert Review of Hematology Jul 2017This review examines the several lines of evidence that support the relationship between myelodysplasia and autoimmunity, i.e. their epidemiologic association, the... (Review)
Review
This review examines the several lines of evidence that support the relationship between myelodysplasia and autoimmunity, i.e. their epidemiologic association, the existence of common immune-mediated physiopathologic mechanisms, and the response to similar immunosuppressive therapies. The same relationship is reviewed here considering idiopathic cytopenia of uncertain significance (ICUS) and idiopathic dysplasia of uncertain significance (IDUS), two recently recognized provisional conditions characterized by isolated/unexplained cytopenia and/or dysplasia in <10% bone marrow cells. Areas covered: The review focuses on alterations of cytokine profiles, telomere/telomerase and toll-like receptors, and on increased myelosuppressive mediators and apoptotic markers in both myelodysplasia and autoimmunity. In addition, the presence of an autoimmune reaction directed against marrow precursors is described in refractory/relapsing autoimmune cytopenias (autoimmune hemolytic anemia, immune thrombocytopenia, chronic idiopathic neutropenia), possibly contributing to their evolution to ICUS/IDUS/bone marrow failure syndromes. Expert commentary: The increasing availability of omics methods has fuelled the discussion on the role of somatic mutations in the pathogenesis of IDUS/ICUS, clonal hematopoiesis of indeterminate potential, and clonal cytopenias of undetermined significance, and in their possible evolution. Even more attracting is the involvement of the genetic background/accumulating somatic mutations in cytopenias with autoimmune alterations.
Topics: Anemia, Aplastic; Anemia, Hemolytic, Autoimmune; Autoimmune Diseases; Autoimmunity; Bone Marrow; Bone Marrow Diseases; Bone Marrow Failure Disorders; Hemoglobinuria, Paroxysmal; Humans; Myelodysplastic Syndromes; Prognosis; Purpura, Thrombocytopenic, Idiopathic; Toll-Like Receptors
PubMed: 28586251
DOI: 10.1080/17474086.2017.1339597 -
American Journal of Medical Genetics.... Jul 2021Sleep-disordered breathing (SDB) is common in patients with skeletal dysplasias. The aim of our study was to analyze SDB and respiratory management in children with rare...
Sleep-disordered breathing (SDB) is common in patients with skeletal dysplasias. The aim of our study was to analyze SDB and respiratory management in children with rare skeletal dysplasias. We performed a retrospective analysis of patients with spondyloepiphyseal dysplasia congenita (SEDC), metatropic dysplasia (MD), spondyloepimetaphyseal dysplasia (SEMD), acrodysostosis (ADO), geleophysic dysplasia (GD), acromicric dysplasia (AD), and spondylocostal dysplasia (SCD) between April 2014 and October 2020. Polygraphic data, clinical management, and patients' outcome were analyzed. Thirty-one patients were included (8 SEDC, 3 MD, 4 SEMD, 1 ADO, 4 GD, 3 AD, and 8 SCD). Sixteen patients had obstructive sleep apnea (OSA): 11 patients (2 with SEDC, 1 with SEMD, 1 with ADO, 1 with GD, 2 with AD, and 4 with SCD) had mild OSA, 2 (1 SEMD and 1 GD) had moderate OSA, and 3 (1 SEDC, 1 MD, 1 SEMD) had severe OSA. Adenotonsillectomy was performed in one patient with SCD and mild OSA, and at a later age in two other patients with ADO and AD. The two patients with moderate OSA were treated with noninvasive ventilation (NIV) because of nocturnal hypoxemia. The three patients with severe OSA were treated with adenotonsillectomy (1 SEDC), adeno-turbinectomy and continuous positive airway pressure (CPAP; 1 MD), and with NIV (1 SEMD) because of nocturnal hypoventilation. OSA and/or alveolar hypoventilation is common in patients with skeletal dysplasias, underlining the importance of systematic screening for SDB. CPAP and NIV are effective treatments for OSA and nocturnal hypoventilation/hypoxemia.
Topics: Adenoidectomy; Adolescent; Adult; Child; Child, Preschool; Continuous Positive Airway Pressure; Dysostoses; Female; Humans; Infant; Intellectual Disability; Male; Osteochondrodysplasias; Polysomnography; Ribs; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Spine; Tonsillectomy; Treatment Outcome; Young Adult
PubMed: 33908178
DOI: 10.1002/ajmg.a.62236 -
Journal of Oral Biology and... 2017Craniometaphyseal Dysplasia (CMD) is a sclerosing osseous dysplasia characterised by hyperostosis of craniofacial and long bones, resulting in distortion and cranial...
Craniometaphyseal Dysplasia (CMD) is a sclerosing osseous dysplasia characterised by hyperostosis of craniofacial and long bones, resulting in distortion and cranial nerve palsies. We present a case report on the management of a 63 year old female with Craniometaphyseal Dysplasia. This report describes an additional clinical manifestation of hypercementosis, which although well recognised in other sclerosing osseous dysplasias, is not reported in the literature for Craniometaphyseal Dysplasia. We discuss established in vivo studies in mice which link the genetic mutations found in Craniometaphyseal Dysplasia to hypercementosis, and how this report describes the same manifestation in humans. This novel finding can aid the clinician in the management of patients with Craniometaphyseal Dysplasia, and complications that can arise in dentoalveolar surgery.
PubMed: 28706789
DOI: 10.1016/j.jobcr.2017.04.007 -
Ceskoslovenska Patologie 2022Evaluation of the dysplastic changes evolving in mucosa of various segments of gastrointestinal tract is a part of routine practice. Morphologically different or... (Review)
Review
Evaluation of the dysplastic changes evolving in mucosa of various segments of gastrointestinal tract is a part of routine practice. Morphologically different or non-conventional types of dysplastic changes are described in the mucosa of gastrointestinal tract besides the most common conventional type of dysplasia. Non-conventional dysplasias can arise de-novo or they can be found in association with chronic gastrointestinal conditions, such as Barretts esophagus, chronic atrophic gastritis, and inflammatory bowel disease. Non-conventional types of dysplasia include serrated, crypt base of foveolar dysplasia and lesions as pyloric or oxyntic gland adenoma. Non-conventional types of dysplasia arising in inflammatory bowel disease represent specific category with broad morphological spectrum of changes. The aim of this work is to present a comprehensive review of morphological characteristics of individual subtypes of non-conventional dysplastic changes with focus on differences and specificity in particular parts of gastrointestinal tract and provide a functional handout for daily diagnostic practice.
Topics: Adenomatous Polyps; Colorectal Neoplasms; Humans; Hyperplasia; Inflammatory Bowel Diseases; Mucous Membrane; Precancerous Conditions
PubMed: 35387456
DOI: No ID Found -
Otology & Neurotology : Official... Mar 2020Describe the first case of cochlear implantation (CI) for auditory rehabilitation of a patient with craniometaphyseal dysplasia (CMD) and progressive mixed hearing loss.
OBJECTIVE
Describe the first case of cochlear implantation (CI) for auditory rehabilitation of a patient with craniometaphyseal dysplasia (CMD) and progressive mixed hearing loss.
PATIENTS
A 65-year-old woman with known autosomal dominant CMD presented with progressive mixed hearing loss and declining benefit from conventional hearing aids. Computed tomography and magnetic resonance imaging revealed hyperostosis of the entire craniofacial skeleton. Hearing evaluation demonstrated pure-tone thresholds in the profound range bilaterally by air conduction, and bone conduction thresholds that matched aided thresholds for her left ear, though testing was somewhat limited by inability to mask at high air-conduction thresholds. CI candidacy testing confirmed poor word and sentence scores in the right ear.
INTERVENTION
Due to the inability to access the cochlea via a conventional mastoidectomy and facial recess approach, cochlear implantation via a postauricular subtotal petrosectomy approach with ear canal overclosure was performed.
MAIN OUTCOME MEASURES
Post-implantation word and sentence testing.
RESULTS
Despite extensive internal auditory canal stenosis, the patient demonstrated excellent early speech understanding results 5 weeks after device activation. Postimplantation audiologic evaluation showed thresholds between 20 and 30 dB HL from 250 to 6000 Hz. Word and sentence testing scores were 76% Consonant-nucleus-consonant in quiet (up from 2% preoperatively) and 77% AzBio sentences in quiet (up from 10% preoperatively).
CONCLUSION
This report describes the first description of CI for CMD. Despite the extensive radiologic abnormalities, the patient has demonstrated excellent benefit from implantation. Further study of rare temporal bone dysplasias, such as CMD, is critical to better characterize the progression of otologic disease and determine optimal treatment.
Topics: Aged; Bone Diseases, Developmental; Cochlear Implantation; Cochlear Implants; Craniofacial Abnormalities; Female; Humans; Hyperostosis; Hypertelorism; Speech Perception; Treatment Outcome
PubMed: 31834875
DOI: 10.1097/MAO.0000000000002504