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World Journal of Radiology Oct 2014Skeletal dysplasias are not uncommon entities and a radiologist is likely to encounter a suspected case of dysplasia in his practice. The correct and early diagnosis of... (Review)
Review
Skeletal dysplasias are not uncommon entities and a radiologist is likely to encounter a suspected case of dysplasia in his practice. The correct and early diagnosis of dysplasia is important for management of complications and for future genetic counselling. While there is an exhaustive classification system on dysplasias, it is important to be familiar with the radiological features of common dysplasias. In this article, we enumerate a radiographic approach to skeletal dysplasias, describe the essential as well as differentiating features of common non-lethal skeletal dysplasias and conclude by presenting working algorithms to either definitively diagnose a particular dysplasia or suggest the most likely differential diagnoses to the referring clinician and thus direct further workup of the patient.
PubMed: 25349664
DOI: 10.4329/wjr.v6.i10.808 -
Children (Basel, Switzerland) Sep 2022The term ectodermal dysplasias (EDs) describes a heterogeneous group of inherited developmental disorders that affect several tissues of ectodermal origin. The most... (Review)
Review
The term ectodermal dysplasias (EDs) describes a heterogeneous group of inherited developmental disorders that affect several tissues of ectodermal origin. The most common form of EDs is hypohidrotic ectodermal dysplasia (HED), which is characterized by hypodontia, hypotrichosis, and partial or total eccrine sweat gland deficiency. HED is estimated to affect at least 1 in 17,000 people worldwide. Patients with HED have characteristic facies with periorbital hyperpigmentation, depressed nasal bridge, malar hypoplasia, and absent or sparse eyebrows and eyelashes. The common ocular features of HED include madarosis, trichiasis, and ocular chronic surface disease due to dry eye syndrome, which manifests clinically with discomfort, photophobia, and redness. Dry eye is common in HED and results from a combination of ocular surface defects: mucus abnormalities (abnormal conjunctival mucinous glands), aqueous tear deficiency (abnormalities in the lacrimal gland) and lipid deficiency (due to the partial or total absence of the meibomian glands; modified sebaceous glands with the tarsal plate). Sight-threatening complications result from ocular surface disease, including corneal ulceration and perforation with subsequent corneal scarring and neovascularization. Rare ocular features have been reported and include bilateral or unilateral congenital cataracts, bilateral glaucoma, chorioretinal atrophy and atresia of the nasolacrimal duct. Recognition of the ocular manifestations of HED is required to perform clinical surveillance, instigate supportive and preventative treatment, and manage ocular complications.
PubMed: 36138666
DOI: 10.3390/children9091357 -
PeerJ 2019Limb bones develop and grow by endochondral ossification, which is regulated by specific cell and molecular pathways. Changes in one or more of these pathways can have...
BACKGROUND
Limb bones develop and grow by endochondral ossification, which is regulated by specific cell and molecular pathways. Changes in one or more of these pathways can have severe effects on normal skeletal development, leading to skeletal dysplasias. Many skeletal dysplasias are known to result from mis-expression of major genes involved in skeletal development, but the etiology of many skeletal dysplasias remains unknown. We investigated the morphology and development of a mouse line with an uncharacterized mutation exhibiting a skeletal dysplasia-like phenotype ().
METHODS
We used µCT scanning and histology to comprehensively characterize the phenotype and its development, and to determine the developmental stage when this phenotype first appears.
RESULTS
mice have shorter limb elements compared to wildtype mice, while clavicles and dermal bones of the skull are not affected. embryos at embryonic stage E14 show shorter limb cartilage condensations. The tibial growth plate in mice is wider than in wildtype, particularly in the proliferative zone, however proliferative chondrocytes show less activity than wildtype mice. Cell proliferation assays and immunohistochemistry against the chondrogenic marker Sox9 suggest relatively lower, spatially-restricted, chondrocyte proliferation activity in . Bone volume and trabecular thickness in tibiae are also decreased compared to wildtype.
DISCUSSION
Our data suggest that the mutation affects endochondral ossification only, with the strongest effects manifesting in more proximal limb structures. The phenotype appears before embryonic stage E14, suggesting that outgrowth and patterning processes may be affected. mice present a combination of skeletal dysplasia-like characteristics not present in any known skeletal dysplasia. Further genomic and molecular analysis will help to identify the genetic basis and precise developmental pathways involved in this unique skeletal dysplasia.
PubMed: 31308998
DOI: 10.7717/peerj.7180 -
BoneKEy Reports 2016Osteoporosis presents as increased susceptibility to fractures due to bone loss and compromised bone microstructure. Osteoporosis mainly affects the elderly population,... (Review)
Review
Osteoporosis presents as increased susceptibility to fractures due to bone loss and compromised bone microstructure. Osteoporosis mainly affects the elderly population, but it is increasingly recognized that compromised bone health with low bone mass and increased fractures may have its onset already in childhood. In such cases, genetic component is likely to contribute more than lifestyle factors to disease onset. During the last decade, our understanding of the genetic determinants of osteoporosis has significantly increased through family studies, candidate gene studies and genome-wide association studies (GWASs). GWASs have led to identification of several genetic loci associated with osteoporosis. A valuable contribution to the research field has been made through studies involving families with childhood-onset rare bone diseases such as osteogenesis imperfecta, osteoporosis-pseudoglioma syndrome and various other skeletal dysplasias with reduced bone mass. Some genes involved in rare low bone mass diseases, such as LRP5 and WNT1, participate in the Wnt/β-catenin pathway, and their discovery has underscored the importance of this pathway for normal skeletal health. The still continuing discovery of gene defects underlying various low bone mass phenotypes contributes to our understanding of normal bone metabolism and enables development of new therapies for osteoporosis.
PubMed: 26793304
DOI: 10.1038/bonekey.2015.143 -
Pediatric Rheumatology Online Journal Jul 2021Acro-osteolysis is a radiographic finding which refers to bone resorption of the distal phalanges. Acro-osteolysis is associated with various conditions and its presence... (Review)
Review
INTRODUCTION
Acro-osteolysis is a radiographic finding which refers to bone resorption of the distal phalanges. Acro-osteolysis is associated with various conditions and its presence should prompt the clinician to search for the underlying etiology. The aim of this review is to discuss disorders with which acro-osteolysis is associated and their distinguishing features, with a focus on the pediatric population.
METHODS
A targeted literature review was performed using the term "acro-osteolysis" in combination with other key terms. The primary search results were supplemented using reference citations. Articles published prior to the year 2000 were included if they described additional associations not encountered in the more recent literature.
RESULTS
Genetic disorders (particularly primary hypertrophic osteoarthropathy and skeletal dysplasias) and rheumatic diseases (particularly psoriatic arthritis and systemic sclerosis) are the most frequently encountered conditions associated with acro-osteolysis in children. Hyperparathyroidism, neuropathy, local trauma and thermal injury, and spinal dysraphism should also be included in the differential diagnosis.
CONCLUSION
Although acro-osteolysis is uncommon, its presence should prompt the clinician to consider a differential diagnosis based on clinical and radiographic features.
Topics: Acro-Osteolysis; Child; Diagnosis, Differential; Humans; Pediatrics; Rheumatology
PubMed: 34261502
DOI: 10.1186/s12969-021-00596-0 -
Pediatric Radiology Nov 2020Skeletal dysplasias have been recognised since recorded history began. The advent of radiography at the beginning of the 20th century and the subsequent introduction of... (Review)
Review
Skeletal dysplasias have been recognised since recorded history began. The advent of radiography at the beginning of the 20th century and the subsequent introduction of departments of radiology have had tremendous impact and allowed conditions to be identified by their specific radiographic phenotypes. This has been enhanced by the addition of cross-sectional modalities (ultrasound, computed tomography and magnetic resonance imaging), which have allowed for prenatal recognition and diagnosis of skeletal dysplasias, and by the recent explosion in identified genes. There are more than 400 recognised skeletal dysplasias, many of which (due to their rarity) the practising clinician (radiologist, paediatrician, geneticist) may never come across. This article provides a historical overview of aids to the radiologic diagnosis of skeletal dysplasias.
Topics: Bone Diseases, Developmental; Bone and Bones; Diagnostic Imaging; Female; Humans; Pregnancy; Prenatal Diagnosis
PubMed: 33135135
DOI: 10.1007/s00247-019-04533-y -
Progress in Rehabilitation Medicine 2021Multiple epiphyseal dysplasia (MED) and spondyloepiphyseal dysplasia (SED) are skeletal dysplasias associated with premature osteoarthritis and short stature. Patients...
OBJECTIVES
Multiple epiphyseal dysplasia (MED) and spondyloepiphyseal dysplasia (SED) are skeletal dysplasias associated with premature osteoarthritis and short stature. Patients with SED often have spinal and ocular problems. Few reports have focused on the health-related quality of life (HRQoL) of patients with skeletal dysplasias associated with premature osteoarthritis. The purpose of this study was to evaluate the HRQoL of adult patients with MED and SED.
METHODS
Questionnaires covering demographics, medical history (cataract, retinal detachment, and osteoarthritis), surgical history (osteotomy and arthroplasty), and the Short Form-36 (SF-36) health survey were sent to all patients with MED and SED with medical records at the investigators' institutions. Among the 27 patients who completed the questionnaire, patients aged 20 years or older were included in this cohort.
RESULTS
The subjects were 18 affected individuals. The physical component summary score (PCS) was significantly lower in the MED and SED groups than in the normal population and tended to deteriorate with age. Conversely, there was a positive correlation between the mental component summary score and age. The role/social component summary score was not correlated with age. MED patients with osteoarthritis had a low PCS. PCS was particularly low in two SED patients with a medical history of cataract, whereas there was no association with a history of retinal detachment or osteoarthritis.
CONCLUSIONS
The physical domain of HRQoL in MED and SED patients significantly deteriorated at a young age. Appropriate medical management of these skeletal dysplasias is required not only for orthopedic functions but also for ocular problems.
PubMed: 34909512
DOI: 10.2490/prm.20210048 -
Human Pathology Dec 2018Gallbladder dysplasia can progress to cancer and may be associated with increased cancer risk at other biliary tract sites. Thus, its accurate identification is relevant...
Gallbladder dysplasia can progress to cancer and may be associated with increased cancer risk at other biliary tract sites. Thus, its accurate identification is relevant both for etiologic understanding and for clinical purposes. Data on the frequency and distribution of gallbladder dysplasia are lacking owing to limited gallbladder sampling and inability to visualize dysplasia grossly. An expert pathology group used consensus criteria to review 140 totally sampled consecutive cholecystectomy specimens from Chilean women. Three cases (2%) revealed incidental invasive carcinoma, all T2, along with high-grade dysplasia (HGD). The surface areas covered by dysplasia or cancer in these cases were 9%, 37%, and 87%. Although the first longitudinal ("diagnostic") section of the whole gallbladder captured HGD or cancer in all 3 cases, the deepest focus of invasive carcinoma was not present in this section. Fourteen additional cases (10%) had low-grade dysplasia (LGD), which was typically very focal (covering <5% of the surface) and most often occurred in the fundus. LGD was not present in the diagnostic section of 5 cases (38%) and would have been missed without additional sampling. None of the cancers or dysplasias were grossly visible. Although HGD and carcinoma are likely to be identified in "diagnostic" sections, accurate staging requires total sampling. LGD is typically very focal and would often be missed in routine practice. To identify cancer precursors, additional sampling, particularly of the fundus, may be warranted. The predominance of LGD in the fundus also provides etiologic insight, supporting the contribution of gallstones and chronic inflammation.
Topics: Adult; Aged; Biopsy; Carcinoma; Chile; Cholecystectomy; Female; Gallbladder; Gallbladder Neoplasms; Humans; Middle Aged; Neoplasm Grading; Neoplasm Staging; Precancerous Conditions; Predictive Value of Tests; Prevalence; Risk Assessment; Risk Factors
PubMed: 30036595
DOI: 10.1016/j.humpath.2018.07.015 -
Journal of the South African Veterinary... Nov 2017Canine hip and elbow dysplasia are major orthopaedic problems prevalent the world over, and South Africa is no exception. Hip and elbow dysplasia phenotypic status is... (Comparative Study)
Comparative Study
Canine hip and elbow dysplasia are major orthopaedic problems prevalent the world over, and South Africa is no exception. Hip and elbow dysplasia phenotypic status is certified by a number of different radiographic schemes in the world. South Africa uses the Fédération Cynologique Internationale system to certify hips, and the International Elbow Working Group scheme to certify elbows. One way of reducing these often crippling conditions is by selective breeding using only dogs with no or marginal dysplastic joints. In South Africa, only seven breeds, including the Rottweiler, have breeding restrictions for hip dysplasia. There are no such restrictions for elbow dysplasia. This study assessed the prevalence of hip and elbow dysplasia over a 9-year-period in the Rottweiler and the Labrador retriever in South Africa as evaluated by official national scrutineers. Records from 1148 Rottweilers and 909 Labrador retrievers were obtained and were graded as normal or dysplastic, and numerical values were also evaluated. Data were compared between the two breeds, males and females as well as over time and were compared with similar data of the Orthopaedic Foundation for Animals in the United States. The prevalence values for hip dysplasia in Rottweilers and Labrador retrievers were 22% and 31%, respectively, whereas for elbow dysplasia the values were 39% and 19%, respectively. In Labrador retrievers, this incidence was much higher than in the American population. Rottweiler hip and elbow dysplasia numerical scores significantly improved over time, whereas in Labrador retrievers, only hip dysplasia showed a minor but significant improvement. This study proved that prescribing minimum breeding requirements, as in the Rottweiler in this study, significantly improved the breeding stock, suggesting that minimum hip and elbow breeding requirements should be initiated for all breeds at risk of these often crippling conditions.
Topics: Animals; Breeding; Dog Diseases; Dogs; Female; Forelimb; Hip Dysplasia, Canine; Joint Dislocations; Male; Phenotype; Prevalence; Radiography; Schools, Veterinary; Severity of Illness Index; South Africa; United States
PubMed: 29227139
DOI: 10.4102/jsava.v88i0.1534 -
Epilepsy Currents Jan 2019Somatic Mutations Activating the mTOR Pathway in Dorsal Telencephalic Progenitors Cause a Continuum of Cortical Dysplasias D'Gama AM, Woodworth MB, Hossain AA, Bizzotto...
Somatic Mutations Activating the mTOR Pathway in Dorsal Telencephalic Progenitors Cause a Continuum of Cortical Dysplasias D'Gama AM, Woodworth MB, Hossain AA, Bizzotto S, Hatem NE, LaCoursiere CM, Najm I, Ying Z, Yang E, Barkovich AJ, Kwiatkowski DJ, Vinters HV, Madsen JR, Mathern GW, Blümcke I, Poduri A, Walsh CA. Cell Rep. 2017;21:3754-3766. Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are epileptogenic neurodevelopmental malformations caused by mutations in mTOR pathway genes. Deep sequencing of these genes in FCD/HME brain tissue identified an etiology in 27 (41%) of 66 cases. Radiographically indistinguishable lesions are caused by somatic activating mutations in AKT3, MTOR, and PIK3CA and germline loss-of-function mutations in DEPDC5, NPRL2, and TSC1/2, including TSC2 mutations in isolated HME demonstrating a "two-hit" model. Mutations in the same gene cause a disease continuum from FCD to HME to bilateral brain overgrowth, reflecting the progenitor cell and developmental time when the mutation occurred. Single-cell sequencing demonstrated mTOR activation in neurons in all lesions. Conditional Pik3ca activation in the mouse cortex showed that mTOR activation in excitatory neurons and glia, but not interneurons, is sufficient for abnormal cortical overgrowth. These data suggest that mTOR activation in dorsal telencephalic progenitors, in some cases specifically the excitatory neuron lineage, causes cortical dysplasia.
PubMed: 30838928
DOI: 10.1177/1535759718822039