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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 -
Cleveland Clinic Journal of Medicine Nov 2016Several key findings in recent years have reshaped our understanding of fibromuscular dysplasia (FMD), an uncommon nonatherosclerotic disease of medium-sized arteries... (Review)
Review
Several key findings in recent years have reshaped our understanding of fibromuscular dysplasia (FMD), an uncommon nonatherosclerotic disease of medium-sized arteries that affects mainly women. While the true prevalence of this disease remains unknown, studies suggest that more people may be affected than previously reported. Better understanding of the clinical manifestations and natural history of FMD and advances in diagnostic imaging have altered the clinical approach to managing patients with this uncommon vascular disease. Although there are a multitude of unanswered questions regarding FMD, this review highlights recent insights and how this information has modified clinical care for those affected.
Topics: Fibromuscular Dysplasia; Humans
PubMed: 27861117
DOI: 10.3949/ccjm.83.s2.06 -
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 -
Frontiers in Endocrinology 2022Skeletal dysplasias comprise a heterogenous group of developmental disorders of skeletal and cartilaginous tissues. Several different forms have been described and the...
Skeletal dysplasias comprise a heterogenous group of developmental disorders of skeletal and cartilaginous tissues. Several different forms have been described and the full spectrum of their clinical manifestations and underlying genetic causes are still incompletely understood. We report a three-generation Finnish family with an unusual, autosomal dominant form of osteochondrodysplasia and an empty sella. Affected individuals (age range 24-44 years) exhibit unusual codfish-shaped vertebrae, severe early-onset and debilitating osteoarthritis and an empty sella without endocrine abnormalities. Clinical characteristics also include mild dysmorphic features, reduced sitting height ratio, and obesity. Whole-exome sequencing excluded known skeletal dysplasias and identified a novel heterozygous missense mutation c.899C>T (p.Thr300Met) in , confirmed by Sanger sequencing. TBX2 is important for development of the skeleton and the brain and three prior reports have described variations in in patients portraying a complex phenotype with vertebral anomalies, craniofacial dysmorphism and endocrine dysfunctions. Our mutation lies near a previously reported disease-causing variant and is predicted pathogenic with deleterious effects on protein function. Our findings expand the current spectrum of skeletal dysplasias, support the association of mutations with skeletal dysplasia and suggest a role for TBX2 in development of the spinal and craniofacial structures and the pituitary gland.
Topics: Abnormalities, Multiple; Bone Diseases, Developmental; Humans; Osteochondrodysplasias; Phenotype; Exome Sequencing
PubMed: 35311234
DOI: 10.3389/fendo.2022.845889 -
Molecular Syndromology Nov 2016The complex anatomy of the skull and face arises from the requirement to support multiple sensory and structural functions. During embryonic development, the diverse... (Review)
Review
The complex anatomy of the skull and face arises from the requirement to support multiple sensory and structural functions. During embryonic development, the diverse component elements of the neuro- and viscerocranium must be generated independently and subsequently united in a manner that sustains and promotes the growth of the brain and sensory organs, while achieving a level of structural integrity necessary for the individual to become a free-living organism. While each of these individual craniofacial components is essential, the cranial and facial midline lies at a structural nexus that unites these disparately derived elements, fusing them into a whole. Defects of the craniofacial midline can have a profound impact on both form and function, manifesting in a diverse array of phenotypes and clinical entities that can be broadly defined as frontonasal dysplasias (FNDs). Recent advances in the identification of the genetic basis of FNDs along with the analysis of developmental mechanisms impacted by these mutations have dramatically altered our understanding of this complex group of conditions.
PubMed: 27920634
DOI: 10.1159/000450533 -
Advances in Clinical and Experimental... Mar 2018Short stature, which is defined as height below 2 standard deviations of the mean height for the age and sex, is one of the most frequent reasons for medical... (Review)
Review
Short stature, which is defined as height below 2 standard deviations of the mean height for the age and sex, is one of the most frequent reasons for medical consultations in children. Short stature may occur due to a constitutional delay in growth, familial short stature or chronic diseases, including many genetic syndromes, metabolic and endocrine disorders. In this article the authors provide a mini-review of the most frequent genetic syndromes associated with short stature that should be taken into account in the differential diagnosis process. Syndromes caused by chromosomal aberrations and gene mutations were divided into 2 main groups: syndromes that are associated with intrauterine growth retardation (IUGR) and those in which IUGR does not occur in the natural history of the patient. The authors described the most important anomalies in each syndrome. Metabolic diseases and skeletal dysplasias were omitted, as they are major separate groups of diseases involving growth delay.
Topics: Body Height; Child; Chromosome Aberrations; Fetal Growth Retardation; Growth Disorders; Humans; Syndrome
PubMed: 29558022
DOI: 10.17219/acem/67051 -
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 -
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 -
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