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BJR Case Reports Apr 2021Desbuquois dysplasia is an autosomal recessive chondrodysplasia characterized by severe micromelic dwarfism, joint laxity, progressive scoliosis, and advanced...
Desbuquois dysplasia is an autosomal recessive chondrodysplasia characterized by severe micromelic dwarfism, joint laxity, progressive scoliosis, and advanced carpotarsal ossification. Two different types of Desbuquois dysplasia have been identified according to the presence (Type 1) or absence (Type 2) of characteristic hand abnormalities including bifid distal thumb phalanx, an extra ossification center distal to the second metacarpal, and interphalangeal joint dislocations. Further, Kim et al have described a milder variant of Desbuquois dysplasia characterized by short stature and hands with short metacarpals, elongated proximal and distal phalanges, and extremely advanced carpal ossification. Here, we present a 19-year-old male patient with Kim variant of Desbuquois dysplasia. He displays almost all of the characteristic skeletal findings of Desbuquois dysplasia along with the characteristic hand features described by Kim et al. This patient is unique in that he also presents sagittal femoral bowing, a radiographic finding that accompanies various skeletal dysplasias but has never been reported in a patient with Desbuquois dysplasia to date.
PubMed: 33841904
DOI: 10.1259/bjrcr.20200137 -
Fetal Diagnosis and Therapy 2023Skeletal dysplasias (SDs) are a heterogeneous group of heritable disorders that affect development of bone and cartilage. Because each SD is individually rare and... (Review)
Review
Skeletal dysplasias (SDs) are a heterogeneous group of heritable disorders that affect development of bone and cartilage. Because each SD is individually rare and because of the heterogeneity within and among disorders, prenatal diagnosis of a specific SD remains challenging. Molecular genetic diagnosis involves invasive testing, which some patients are not amenable to. Further, genetic analysis is time consuming, and results may not become available in time to make pregnancy management decisions. Low-dose fetal CT can aid in the prenatal evaluation of SDs. The main downside is the low but true risk of fetal radiation exposure. As such, fetal CT should only be performed when there is concern for a severe skeletal dysplasia and the diagnosis is in question after a detailed ultrasound or if molecular genetic testing is unavailable and when prenatal diagnosis may affect management or counseling. Fetal CT should be obtained after consultation with geneticists, maternal-fetal medicine specialists, and fetal radiologists, and sometimes orthopedic surgeons or neonatologists. The purpose of this study was to review the technique of and indications for fetal CT, as well as discuss fetal radiation risk. Illustrative cases will demonstrate when and how CT may be helpful in the diagnosis of SDs.
Topics: Female; Pregnancy; Humans; Bone Diseases, Developmental; Prenatal Diagnosis; Ultrasonography; Fetus; Tomography, X-Ray Computed; Ultrasonography, Prenatal
PubMed: 36948169
DOI: 10.1159/000528692 -
Human Pathology Jan 2024Gastric metaplasia in colonic mucosa with inflammatory bowel disease (IBD) develops as an adaptation mechanism. The association between gastric metaplasia and...
Gastric metaplasia in colonic mucosa with inflammatory bowel disease (IBD) develops as an adaptation mechanism. The association between gastric metaplasia and nonconventional and/or conventional dysplasia as precursors of colitis-associated colorectal cancer is unknown. To address this question, we retrospectively reviewed a series of 33 IBD colectomies to identify gastric metaplasia in 76 precursor lesions. We obtained 61 nonconventional and 15 conventional dysplasias. Among nonconventional dysplasia, 31 (50.8 %) were low-grade (LGD), 4 (6.5 %) were high-grade (HGD), 9 (14.8 %) had both LGD and HGD, and 17 (27.9 %) had no dysplasia (ND), while 14 (93 %) conventional dysplasias had LGD, and 1 (7 %) had LGD and HGD. Gastric metaplasia was assessed by concomitant immunoexpression of MUC5AC and loss of CDX2 staining. Expression of a p53-mut pattern was considered as a surrogate for gene mutation, and complete loss of MLH1 staining as presence of MLH1 hypermethylation. In nonconventional dysplasia, MUC5AC immunoexpression decreased as the degree of dysplasia increased, being 78 % in LGD and 39 % in HGD (p = 0.006). CDX2 was lost in epithelial glands with high expression of MUC5AC (p < 0.001). The p53-mut pattern was observed in 77 % HGD, 45 % LGD, and in 6 % with ND (p < 0.001). Neither nonconventional nor conventional dysplasia showed complete loss of MLH1 staining. Gastric metaplasia was also present in mucosa adjacent to nonconventional dysplasia with chronic changes or active inflammation. Our results show that gastric metaplasia appears in IBD-inflamed colon mucosa, it is the substrate of most nonconventional dysplasia and occurs prior to p53 alterations.
Topics: Humans; Retrospective Studies; Tumor Suppressor Protein p53; Inflammatory Bowel Diseases; Colon; Hyperplasia; Metaplasia; Precancerous Conditions
PubMed: 38000679
DOI: 10.1016/j.humpath.2023.11.011 -
Neurobiology of Disease Oct 2023De novo somatic (post-zygotic) gene mutations affecting neuroglial progenitor cell types in embryonic cerebral cortex are increasingly identified in patients with drug... (Review)
Review
De novo somatic (post-zygotic) gene mutations affecting neuroglial progenitor cell types in embryonic cerebral cortex are increasingly identified in patients with drug resistant epilepsy (DRE) associated with malformations of cortical development, in particular, focal cortical dysplasias (FCD). Somatic variants in at least 16 genes have been linked to FCD type II, all encoding components of the mechanistic target of rapamycin (mTOR) pathway. FCD type II is characterized histopathologically by cytomegalic dysmorphic neurons and balloon cells. In contrast, the molecular pathogenesis of FCD I subtypes is less well understood, and histological features are characterized by alterations in columnar or laminar organization without cytomegalic dysmorphic neurons or balloon cells. In 2018, we reported somatic mutations in Solute Carrier Family 35 member A2 (SLC35A2) linked to DRE underlying FCD type I and subsequently to a new histopathological phenotype: excess oligodendrocytes and heterotopic neurons in subcortical white matter known as MOGHE (mild malformation of cortical development with oligodendroglial hyperplasia). These discoveries opened the door to studies linking somatic mutations to FCD. In this review, we discuss the biology of SLC35A2 somatic mutations in epilepsy in FCD and MOGHE, and insights into SLC35A2 epilepsy pathogenesis, describing progress to date and critical areas for investigation.
Topics: Humans; Drug Resistant Epilepsy; Focal Cortical Dysplasia; Epilepsy; Malformations of Cortical Development, Group I; Malformations of Cortical Development
PubMed: 37739137
DOI: 10.1016/j.nbd.2023.106299 -
Global Medical Genetics Jun 2021Bone is a specialized form of connective tissue, which is mineralized and made up of approximately 28% type I collagen and 5% noncollagenous matrix proteins. The... (Review)
Review
Bone is a specialized form of connective tissue, which is mineralized and made up of approximately 28% type I collagen and 5% noncollagenous matrix proteins. The properties of bone are very remarkable, because it is a dynamic tissue, undergoing constant renewal in response to mechanical, nutritional, and hormonal influences. In 1978, "The International Nomenclature of Constitutional Diseases of Bone" divided bone disorders into two broad groups: osteochondrodysplasias and dysostoses. The osteochondrodysplasia group is further subdivided into two categories: dysplasias (abnormalities of bone and/or cartilage growth) and osteodystrophies (abnormalities of bone and/or cartilage texture). The dysplasias form the largest group of bone disorders, hence the loose term "skeletal dysplasia" that is often incorrectly used when referring to a condition that is in reality an osteodystrophy or dysostosis. The word "dystrophy" implies any condition of abnormal development. "Osteodystrophies," as their name implies, are disturbances in the growth of bone. It is also known as osteodystrophia. It includes bone diseases that are neither inflammatory nor neoplastic but may be genetic, metabolic, or of unknown origin. Recent studies have shown that bone influences the activity of other organs, and the bone is also influenced by other organs and systems of the body, providing new insights and evidencing the complexity and dynamic nature of bone tissue. The 1,25-dihydroxyvitamin D3, or simply vitamin D, in association with other hormones and minerals, is responsible for mediating the intestinal absorption of calcium, which influences plasma calcium levels and bone metabolism. Diagnosis of the specific osteodystrophy type is a rather complex process and various biochemical markers and radiographic findings are used, so as to facilitate this condition. For diagnosis, we must consider the possibility of lesions related to bone metabolism altered by chronic renal failure (CRI), such as the different types of osteodystrophies, and differentiate from other possible neoplastic and/or inflammatory pathologies. It is important that the dentist must be aware of patients medical history, suffering from any systemic diseases, and identify the interference of the drugs and treatments to control them, so that we can able to perform the correct diagnosis and propose the most adequate treatment and outcomes of the individuals with bone lesions.
PubMed: 33987622
DOI: 10.1055/s-0041-1724105 -
Radiographics : a Review Publication of... 2021Type II collagen is a major component of the cartilage matrix. Pathogenic variants (ie, disease-causing aberrations) in the type II collagen gene lead to an abnormal...
Type II collagen is a major component of the cartilage matrix. Pathogenic variants (ie, disease-causing aberrations) in the type II collagen gene lead to an abnormal structure of type II collagen, causing a large group of skeletal dysplasias termed Because type II collagen is also located in the vitreous body of the eyes and inner ears, type II collagenopathies are commonly associated with vitreoretinal degeneration and hearing impairment. Type II collagenopathies can be radiologically divided into two major groups: the spondyloepiphyseal dysplasia congenita (SEDC) group and the Kniest-Stickler group. The SEDC group is characterized by delayed ossification of the juxtatruncal bones, including pear-shaped vertebrae. These collagenopathies comprise achondrogenesis type 2, hypochondrogenesis, SEDC, and other uncommon subtypes. The Kniest-Stickler group is characterized by disordered tubular bone growth that leads to "dumbbell" deformities. It comprises Kniest dysplasia and Stickler dysplasia type 1, whose radiographic manifestations overlap with those of type XI collagenopathies (a group of disorders due to abnormal type XI collagen) such as Stickler dysplasia types 2 and 3. This phenotypic overlap is caused by type II and type XI collagen molecules sharing part of the same connective tissues. The authors describe the diagnostic pathways to type II and type XI collagenopathies and the associated differential diagnoses. In addition, they review the clinical features and genetic bases of these conditions, which radiologists should know to participate in multidisciplinary care and translational research. RSNA, 2020.
Topics: Achondroplasia; Cartilage; Collagen Diseases; Humans; Hyaline Membrane Disease; Infant, Newborn; Osteochondrodysplasias
PubMed: 33186059
DOI: 10.1148/rg.2021200075 -
Neurosurgery Clinics of North America Jan 2022Achondroplasia is the most common of skeletal dysplasias and is caused by a defect in endochondral bone formation. In addition to skeletal deformities, patients with... (Review)
Review
Achondroplasia is the most common of skeletal dysplasias and is caused by a defect in endochondral bone formation. In addition to skeletal deformities, patients with achondroplasia possess significant abnormalities of the axial skeleton, including small skull base with a narrowed foramen magnum and small vertebral bodies with shortened pedicles. Consequently, patients with achondroplasia are at risk of several severe neurologic conditions, such as cervicomedullary compression, spinal stenosis, and hydrocephalus, which frequently require the attention of a neurosurgeon. This article provides an updated review on the neurosurgical evaluation and care of children with Achondroplasia.
Topics: Achondroplasia; Child; Constriction, Pathologic; Foramen Magnum; Humans; Hydrocephalus; Infant; Spinal Stenosis
PubMed: 34801138
DOI: 10.1016/j.nec.2021.09.003 -
Neurosurgery Clinics of North America Jan 2022Neurosurgical patients with genetic syndromes often receive care from multidisciplinary teams. Successful models range from multiple providers in one clinic space seeing... (Review)
Review
Neurosurgical patients with genetic syndromes often receive care from multidisciplinary teams. Successful models range from multiple providers in one clinic space seeing a patient together to specialists located at different institutions working together. Collaboration and bidirectional communication are key. Multidisciplinary care improves outcomes and patient satisfaction. Choosing the goal of the clinic, using ancillary staff, and obtaining institutional buy-in are important initial first steps to establishing a multidisciplinary team clinic. Multidisciplinary teams can leverage technology to expand care via telehealth in multidisciplinary clinics and more vitally communication between providers on the team.
Topics: Communication; Humans; Patient Care Team; Patient Satisfaction; Syndrome
PubMed: 34801144
DOI: 10.1016/j.nec.2021.09.002 -
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 -
Brain : a Journal of Neurology Nov 2022One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle...
One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted 'gold-standard' subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.
Topics: Humans; Retrospective Studies; Malformations of Cortical Development; Epilepsy; Magnetic Resonance Imaging; Machine Learning; Epilepsies, Partial
PubMed: 35953082
DOI: 10.1093/brain/awac224