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Postepy Higieny I Medycyny... Oct 2015Various forms of bony deformations and dysplasias are often present in the facial skeleton. Bone defects can be either localized or general. Quite often they are not... (Review)
Review
Various forms of bony deformations and dysplasias are often present in the facial skeleton. Bone defects can be either localized or general. Quite often they are not only present in the skull but also can be found in other parts of the skeleton. In many cases the presence and levels of specific bone markers should be measured in order to fully describe their activity and presence in the skeleton. Fibrous dysplasia (FD) is the most common one in the facial skeleton; however, other bone deformations regarding bone growth and activity can also be present. Every clinician should be aware of all common, rare and uncommon bony diseases and conditions such as cherubism, Paget's disease, osteogenesis imperfecta and others related to genetic conditions. We present standard (calcium, parathyroid hormone, calcitonin, alkaline phosphatase, vitamin D) and specialized bone markers (pyridinium, deoxypyridinium, hydroxyproline, RANKL/RANK/OPG pathway, growth hormone, insulin-like growth hormone-1) that can be used to evaluate, measure or describe the processes occurring in craniofacial bones.
Topics: Biomarkers; Bone and Bones; Calcium; Cherubism; Clinical Chemistry Tests; Craniofacial Abnormalities; Humans; Osteitis Deformans; Osteogenesis Imperfecta
PubMed: 26561843
DOI: 10.5604/17322693.1176768 -
Orphanet Journal of Rare Diseases Dec 2021Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface...
Growth in achondroplasia including stature, weight, weight-for-height and head circumference from CLARITY: achondroplasia natural history study-a multi-center retrospective cohort study of achondroplasia in the US.
BACKGROUND
Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments from birth through 18 years for clinical use and research for achondroplasia patients.
METHODS
All available retrospective anthropometry data including length/height, weight and head circumference from achondroplasia patients were collected at 4 US skeletal dysplasia centers (Johns Hopkins University, AI DuPont Hospital for Children, McGovern Medical School University of Texas Health, University of Wisconsin School of Medicine and Public Health). Weight-for-age values beyond 3 SD above the mean were excluded from the weight-for-height and weight-for-age curves to create a stricter tool for weight assessment in this population.
RESULTS
Over 37,000 length/height, weight and head circumference measures from 1374 patients with achondroplasia from birth through 75 years of age were compiled in a REDCap database. Stature and weight data from birth through 18 years of age and head circumference from birth through 5 years of age were utilized to construct new length/height-for-age, weight-for-age, head circumference-for-age and weight-for-height curves.
CONCLUSION
Achondroplasia-specific growth curves are essential for clinical care of growing infants and children with this condition. In an effort to provide prescriptive, rather than purely descriptive, references for weight in this population, extreme weight values were omitted from the weight-for-age and weight-for-height curves. This well-phenotyped cohort may be studied with other global achondroplasia populations (e.g. Europe, Argentina, Australia, Japan) to gain further insight into environmental or ethnic influences on growth.
Topics: Achondroplasia; Body Height; Child; Cohort Studies; Growth Charts; Humans; Infant; Retrospective Studies
PubMed: 34949201
DOI: 10.1186/s13023-021-02141-4 -
Epilepsia Nov 2015Our inability to adequately treat many patients with refractory epilepsy caused by focal cortical dysplasia (FCD), surgical inaccessibility and failures are significant... (Review)
Review
Our inability to adequately treat many patients with refractory epilepsy caused by focal cortical dysplasia (FCD), surgical inaccessibility and failures are significant clinical drawbacks. The targeting of physiologic features of epileptogenesis in FCD and colocalizing functionality has enhanced completeness of surgical resection, the main determinant of outcome. Electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) and magnetoencephalography are helpful in guiding electrode implantation and surgical treatment, and high-frequency oscillations help defining the extent of the epileptogenic dysplasia. Ultra high-field MRI has a role in understanding the laminar organization of the cortex, and fluorodeoxyglucose-positron emission tomography (FDG-PET) is highly sensitive for detecting FCD in MRI-negative cases. Multimodal imaging is clinically valuable, either by improving the rate of postoperative seizure freedom or by reducing postoperative deficits. However, there is no level 1 evidence that it improves outcomes. Proof for a specific effect of antiepileptic drugs (AEDs) in FCD is lacking. Pathogenic mutations recently described in mammalian target of rapamycin (mTOR) genes in FCD have yielded important insights into novel treatment options with mTOR inhibitors, which might represent an example of personalized treatment of epilepsy based on the known mechanisms of disease. The ketogenic diet (KD) has been demonstrated to be particularly effective in children with epilepsy caused by structural abnormalities, especially FCD. It attenuates epigenetic chromatin modifications, a master regulator for gene expression and functional adaptation of the cell, thereby modifying disease progression. This could imply lasting benefit of dietary manipulation. Neurostimulation techniques have produced variable clinical outcomes in FCD. In widespread dysplasias, vagus nerve stimulation (VNS) has achieved responder rates >50%; however, the efficacy of noninvasive cranial nerve stimulation modalities such as transcutaneous VNS (tVNS) and noninvasive (nVNS) requires further study. Although review of current strategies underscores the serious shortcomings of treatment-resistant cases, initial evidence from novel approaches suggests that future success is possible.
Topics: Anticonvulsants; Drug Resistant Epilepsy; Electroencephalography; Humans; Magnetic Resonance Imaging; Malformations of Cortical Development; Treatment Outcome
PubMed: 26434565
DOI: 10.1111/epi.13200 -
Radiology Case Reports May 2023Fibrocartilaginous dysplasia has been described as a rare variant of fibrous dysplasia. This lesion will appear in imaging as ground glass matrix similar to fibrous...
Fibrocartilaginous dysplasia has been described as a rare variant of fibrous dysplasia. This lesion will appear in imaging as ground glass matrix similar to fibrous dysplasia, but it will also show rings and arcs calcifications. In turn, this can lead to misdiagnosing fibrocartilaginous dysplasia as primary cartilaginous lesion such as enchondroma or chondrosarcoma, neccesating histopathological confirmation. We report a case of fibrocartilaginous dysplasia in a 19 years old male with polyostotic fibrous dysplasia with prior pathologic fracture of the left femur. The patient presented with progressive swelling of the left thigh, imaging was done and showed enlargement of the fibrous dysplasia in the left femur with new rings and arcs matrix mineralization. The lesion was biopsied and microscopic evaluation revealed mainly cartilage islands with fibro-osseous tissue. We also discuss the possible origin of the cartilaginous component in this lesion, and its clinical course.
PubMed: 36926535
DOI: 10.1016/j.radcr.2023.01.074 -
Disease Models & Mechanisms May 2016The gastrointestinal tract of complex metazoans is highly compartmentalized. It is lined by a series of specialized epithelia that are regenerated by specific... (Review)
Review
The gastrointestinal tract of complex metazoans is highly compartmentalized. It is lined by a series of specialized epithelia that are regenerated by specific populations of stem cells. To maintain tissue homeostasis, the proliferative activity of stem and/or progenitor cells has to be carefully controlled and coordinated with regionally distinct programs of differentiation. Metaplasias and dysplasias, precancerous lesions that commonly occur in the human gastrointestinal tract, are often associated with the aberrant proliferation and differentiation of stem and/or progenitor cells. The increasingly sophisticated characterization of stem cells in the gastrointestinal tract of mammals and of the fruit fly Drosophila has provided important new insights into these processes and into the mechanisms that drive epithelial dysfunction. In this Review, we discuss recent advances in our understanding of the establishment, maintenance and regulation of diverse intestinal stem cell lineages in the gastrointestinal tract of Drosophila and mice. We also discuss the field's current understanding of the pathogenesis of epithelial dysfunctions.
Topics: Animals; Disease; Drosophila melanogaster; Gastrointestinal Tract; Health; Humans; Signal Transduction; Stem Cells
PubMed: 27112333
DOI: 10.1242/dmm.024232 -
NeuroImage. Clinical 2017Focal cortical dysplasias (FCDs) are a range of malformations of cortical development each with specific histopathological features. Conventional radiological assessment... (Review)
Review
Focal cortical dysplasias (FCDs) are a range of malformations of cortical development each with specific histopathological features. Conventional radiological assessment of standard structural MRI is useful for the localization of lesions but is unable to accurately predict the histopathological features. Quantitative MRI offers the possibility to probe tissue biophysical properties in vivo and may bridge the gap between radiological assessment and ex-vivo histology. This review will cover histological, genetic and radiological features of FCD following the ILAE classification and will explain how quantitative voxel- and surface-based techniques can characterise these features. We will provide an overview of the quantitative MRI measures available, their link with biophysical properties and finally the potential application of quantitative MRI to the problem of FCD subtyping. Future research linking quantitative MRI to FCD histological properties should improve clinical protocols, allow better characterisation of lesions in vivo and tailored surgical planning to the individual.
Topics: Humans; Magnetic Resonance Imaging; Malformations of Cortical Development; Phenotype
PubMed: 28491496
DOI: 10.1016/j.nicl.2017.04.017 -
Frontiers in Endocrinology 2020Skeletal dysplasias are a diverse group of heritable diseases affecting bone and cartilage growth. Throughout the years, the molecular defect underlying many of the... (Review)
Review
Skeletal dysplasias are a diverse group of heritable diseases affecting bone and cartilage growth. Throughout the years, the molecular defect underlying many of the diseases has been identified. These identifications led to novel insights in the mechanisms regulating bone and cartilage growth and homeostasis. One of the pathways that is clearly important during skeletal development and bone homeostasis is the Wingless and int-1 (WNT) signaling pathway. So far, three different WNT signaling pathways have been described, which are all activated by binding of the WNT ligands to the Frizzled (FZD) receptors. In this review, we discuss the skeletal disorders that are included in the latest nosology of skeletal disorders and that are caused by genetic defects involving the WNT signaling pathway. The number of skeletal disorders caused by defects in WNT signaling genes and the clinical phenotype associated with these disorders illustrate the importance of the WNT signaling pathway during skeletal development as well as later on in life to maintain bone mass. The knowledge gained through the identification of the genes underlying these monogenic conditions is used for the identification of novel therapeutic targets. For example, the genes underlying disorders with altered bone mass are all involved in the canonical WNT signaling pathway. Consequently, targeting this pathway is one of the major strategies to increase bone mass in patients with osteoporosis. In addition to increasing the insights in the pathways regulating skeletal development and bone homeostasis, knowledge of rare skeletal dysplasias can also be used to predict possible adverse effects of these novel drug targets. Therefore, this review gives an overview of the skeletal and extra-skeletal phenotype of the different skeletal disorders linked to the WNT signaling pathway.
Topics: Animals; Bone Diseases; Bone and Bones; Genetic Diseases, Inborn; Humans; Musculoskeletal Abnormalities; Wnt Signaling Pathway
PubMed: 32328030
DOI: 10.3389/fendo.2020.00165 -
Journal of Bone and Mineral Research :... May 2023Lethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356), also called dysplastic cortical hyperostosis, Al-Gazali type, is an ultra-rare disorder previously...
Lethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356), also called dysplastic cortical hyperostosis, Al-Gazali type, is an ultra-rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al-Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short-limb skeletal dysplasia Al-Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly. Biallelic disease-causing variants in ADAMTSL2 were detected using massively parallel sequencing (MPS) and Sanger sequencing techniques. Six individuals were compound heterozygous and one individual was homozygous for pathogenic variants in ADAMTSL2. In one of the families, pathogenic variants were detected in parental samples only. Overall, this study sheds light on the genetic cause of Al-Gazali skeletal dysplasia and identifies it as a semi-lethal part of the spectrum of ADAMTSL2-related disorders. Furthermore, we highlight the importance of meticulous analysis of the pseudogene region of ADAMTSL2 where disease-causing variants might be located. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Bone Diseases, Developmental; Limb Deformities, Congenital; Osteochondrodysplasias; Bone and Bones; Homozygote; ADAMTS Proteins
PubMed: 36896612
DOI: 10.1002/jbmr.4799 -
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 -
Modern Pathology : An Official Journal... Jun 2020Endoscopic resection (ER) allows optimal staging with potential cure of early-stage luminal malignancies while maintaining organ preservation. ER and surgery are... (Review)
Review
Endoscopic resection (ER) allows optimal staging with potential cure of early-stage luminal malignancies while maintaining organ preservation. ER and surgery are non-competing but complementary therapeutic options. In addition, histological examination of ER specimens can either confirm or refine the pre-procedure diagnosis. ER is used for the treatment of Barrett's related early carcinomas and dysplasias, early-esophageal squamous cell carcinomas and dysplasias, early gastric carcinomas and dysplasia, as well as low-risk submucosal invasive carcinomas (LR-SMIC) and, large laterally spreading adenomas of the colon. For invasive lesions, histological risk factors predict risk of lymph node metastasis and residual disease at the ER site. Important pathological risk factors predictive of lymph node metastasis are depth of tumor invasion, poor differentiation, and lymphovascular invasion. Complete resection with negative margins is critical to avoid local recurrences. For non-invasive lesions, complete resection is curative. Therefore, a systematic approach for handling and assessing ER specimens is recommended to evaluate all above key prognostic features appropriately. Correct handling starts with pinning the specimen before fixation, meticulous macroscopic assessment with orientation of appropriate margins, systematic sectioning, and microscopic assessment of the entire specimen. Microscopic examination should be thorough for accurate assessment of all pathological risk factors and margin assessment. Site-specific issues such as duplication of muscularis mucosa of the esophagus, challenges of assessing ampullectomy specimens and site-specific differences of staging of early carcinomas throughout the gastrointestinal tract (GI) tract should be given special consideration. Finally, a standard, comprehensive pathology report that allows optimal staging with potential cure of early-stage malignancies or better stratification and guidance for additional treatment should be provided.
Topics: Gastrointestinal Neoplasms; Gastrointestinal Tract; Humans; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis
PubMed: 31907377
DOI: 10.1038/s41379-019-0443-1