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Orthopaedics & Traumatology, Surgery &... Feb 2022Trochlear dysplasia consists in deficient trochlear concavity, giving rise to a flat or convex trochlea, and is the main risk factor for patellar dislocation. Surgical... (Review)
Review
Trochlear dysplasia consists in deficient trochlear concavity, giving rise to a flat or convex trochlea, and is the main risk factor for patellar dislocation. Surgical indications depend on familiarity with trochlear dysplasias, and especially those of high grade, identified on clinical examination and standard and cross-sectional imaging, and on quantification of associated instability factors. Treatment strategy is accordingly determined "à la carte" to correct these factors one by one. Sulcus deepening trochleoplasty corrects the morphology and is the appropriate etiological treatment. It gives good results in terms of recurrence of dislocation, but tends to cause knee stiffness and patellofemoral osteoarthritis. Indications are based on objective patellar instability associated to high-grade B or D dysplasia. Medial patellofemoral ligament reconstruction should be systematically associated. The lateral retinaculum is systematically sectioned, as patellar tilt is never reducible in such high-grade dysplasia. Trochleoplasty corrects the sulcus defect, resolves protrusion and enables proximal realignment. The main complications are stiffness and pain due to persistence or onset of cartilage lesions. Trochleoplasty is indicated: 1) in first line for objective patellar instability associated with high-grade dysplasia; or 2) for recurrence in high-grade dysplasia previously managed by other surgery. The aim of the present study was to review the literature on trochleoplasty and address the following questions: how to define high-grade dysplasia? What are the key clinical and radiologic points? What are the risk factors for patellar dislocation? What trochleoplasty techniques are available? What results can be expected? Level of evidence: V; expert opinion.
Topics: Femur; Humans; Joint Instability; Ligaments, Articular; Patellar Dislocation; Patellofemoral Joint
PubMed: 34863959
DOI: 10.1016/j.otsr.2021.103160 -
Case Reports in Obstetrics and... 2022Robinow syndrome is a genetically heterogenous syndrome that exhibits great pleiotropy, involving skeletal genital, cardiac, and craniofacial developmental anomalies....
Robinow syndrome is a genetically heterogenous syndrome that exhibits great pleiotropy, involving skeletal genital, cardiac, and craniofacial developmental anomalies. Fertility is not always compromised, and many individuals may be able to have a healthy pregnancy. Similar to other more common skeletal dysplasias and growth disorders such as achondroplasia, there are several challenges to be addressed in managing physiologic differences that occur in the context of pregnancy, and published literature centers on pregnant people with achondroplasia. We present a patient with Robinow syndrome ( variant), follow her clinical course through three of her pregnancies (one 20-week loss followed by two preterm cesarean deliveries at 36-week gestation), and highlight the major obstetrical considerations in her individualized care.
PubMed: 35909981
DOI: 10.1155/2022/6481517 -
American Journal of Human Genetics Sep 2023Sclerosing skeletal dysplasias result from an imbalance between bone formation and resorption. We identified three homozygous, C-terminally truncating AXIN1 variants in...
Sclerosing skeletal dysplasias result from an imbalance between bone formation and resorption. We identified three homozygous, C-terminally truncating AXIN1 variants in seven individuals from four families affected by macrocephaly, cranial hyperostosis, and vertebral endplate sclerosis. Other frequent findings included hip dysplasia, heart malformations, variable developmental delay, and hematological anomalies. In line with AXIN1 being a central component of the β-catenin destruction complex, analyses of primary and genome-edited cells harboring the truncating variants revealed enhanced basal canonical Wnt pathway activity. All three AXIN1-truncating variants resulted in reduced protein levels and impaired AXIN1 polymerization mediated by its C-terminal DIX domain but partially retained Wnt-inhibitory function upon overexpression. Addition of a tankyrase inhibitor attenuated Wnt overactivity in the AXIN1-mutant model systems. Our data suggest that AXIN1 coordinates the action of osteoblasts and osteoclasts and that tankyrase inhibitors can attenuate the effects of AXIN1 hypomorphic variants.
Topics: Humans; Tankyrases; Hip Dislocation; Axin Protein; Wnt Signaling Pathway; Osteosclerosis; beta Catenin
PubMed: 37582359
DOI: 10.1016/j.ajhg.2023.07.011 -
Frontiers in Oral Health 2024Oral epithelial dysplasia associated with high-risk HPV infection has received different names since its initial description, such as oral Bowenoid lesions,... (Review)
Review
Oral epithelial dysplasia associated with high-risk HPV infection has received different names since its initial description, such as oral Bowenoid lesions, HPV-associated intraepithelial neoplasia, and oral koilocytic dysplasia. Some features, identified in more or less quantity in some of the descriptions, like apoptotic keratinocytes, karyorrhexis, and mitosoid figures, are intricately connected to viral transcriptional status and, consequently, viral load. Since the variety in terminology has introduced diagnostic confusion within medical and research communities, establishing a uniform and standardized approach to diagnosing HPV-oral epithelial dysplasia is crucial for accurate and early diagnoses and holds significant implications for patient outcomes, particularly in high-risk individuals.
PubMed: 38433947
DOI: 10.3389/froh.2024.1363556 -
International Journal of Biological... 2020-related disorders represent a heterogeneous group of skeletal dysplasias with a wide phenotypic spectrum. Our aim is to characterize the clinical and molecular...
-related disorders represent a heterogeneous group of skeletal dysplasias with a wide phenotypic spectrum. Our aim is to characterize the clinical and molecular phenotypes of Chinese patients with -related dysplasia and to explore their phenotype-genotype relations. Clinical data were collected, physical examinations were conducted, and X-ray radiography and genetic analyses were performed in ten families involving 29 patients with -related dysplasia. Nine mutations were identified in , including five novel (c.816+6C>T, p.Gly246Arg, p.Gly678Glu, p.Gly1014Val and p.Ter1488Gln) and four reported previously (p.Gly204Val, p.Arg275Cys, p.Gly504Ser and p.Arg719Cys). Based on clinical features and molecular mutations, the ten families were classified into five definite -related disorders: four families with spondyloepiphyseal dysplasia congenita (SEDC), three with osteoarthritis with mild chondrodysplasia (OSCPD), one with Czech dysplasia, one with Kniest dysplasia, and one with epiphyseal dysplasia, multiple, with myopia and deafness (EDMMD). Based on genetic testing results, prenatal diagnosis and genetic counseling were accomplished for one female proband with OSCDP. Chinese patients with OSCDP, Czech dysplasia and EDMMD caused by mutations were first reported, expanding the spectrum of mutations and the phenotype of -related disorders and providing further evidence for the phenotype-genotype relations, which may help improve procreative management of -related disorders.
Topics: Adolescent; Adult; Aged; Asian People; Child; Child, Preschool; Cleft Palate; Collagen Diseases; Collagen Type II; Dwarfism; Face; Female; Genotype; Humans; Hyaline Membrane Disease; Male; Middle Aged; Mutation; Osteoarthritis; Osteochondrodysplasias; Phenotype; Toes; Young Adult
PubMed: 32071555
DOI: 10.7150/ijbs.38811 -
ELife Feb 2023Mutations in the TRPV4 ion channel can lead to a range of skeletal dysplasias. However, the mechanisms by which TRPV4 mutations lead to distinct disease severity remain...
Mutations in the TRPV4 ion channel can lead to a range of skeletal dysplasias. However, the mechanisms by which TRPV4 mutations lead to distinct disease severity remain unknown. Here, we use CRISPR-Cas9-edited human-induced pluripotent stem cells (hiPSCs) harboring either the mild V620I or lethal T89I mutations to elucidate the differential effects on channel function and chondrogenic differentiation. We found that hiPSC-derived chondrocytes with the V620I mutation exhibited increased basal currents through TRPV4. However, both mutations showed more rapid calcium signaling with a reduced overall magnitude in response to TRPV4 agonist GSK1016790A compared to wildtype (WT). There were no differences in overall cartilaginous matrix production, but the V620I mutation resulted in reduced mechanical properties of cartilage matrix later in chondrogenesis. mRNA sequencing revealed that both mutations up-regulated several anterior genes and down-regulated antioxidant genes and throughout chondrogenesis. BMP4 treatment up-regulated several essential hypertrophic genes in WT chondrocytes; however, this hypertrophic maturation response was inhibited in mutant chondrocytes. These results indicate that the TRPV4 mutations alter BMP signaling in chondrocytes and prevent proper chondrocyte hypertrophy, as a potential mechanism for dysfunctional skeletal development. Our findings provide potential therapeutic targets for developing treatments for TRPV4-mediated skeletal dysplasias.
Topics: Humans; Chondrocytes; Induced Pluripotent Stem Cells; TRPV Cation Channels; Osteochondrodysplasias; Cell Differentiation; Mutation; Hypertrophy; Chondrogenesis
PubMed: 36810131
DOI: 10.7554/eLife.71154 -
Chronic Illness Dec 2022Fibrous dysplasia is a rare bone disorder that causes deformity, fractures, and pain that typically manifests in childhood and persists as a chronic illness. This study...
OBJECTIVES
Fibrous dysplasia is a rare bone disorder that causes deformity, fractures, and pain that typically manifests in childhood and persists as a chronic illness. This study evaluates adult patients with fibrous dysplasia and McCune Albright syndrome to determine whether their quality of life differs from the general population and varies in relation to disease severity and lesion location.
METHODS
This study uses data from the online self-report Fibrous Dysplasia Foundation Patient Registry and operationalizes quality of life using PRO measures: SF-36, Hospital Anxiety and Depression scale, Neuro-Quality of Life Stigma scale, and the Brief Pain Inventory.
RESULTS
One hundred and ninety seven adults, 90% white, 84% women, constitute the sample. Mean scores for all SF-36 domains and the Neuro Q stigma scale were significantly below population benchmarks. A large minority registered moderate to severe levels of anxiety and depression. Group differences were not significant across most of the SF-36 domains but were associated with experienced stigma.
DISCUSSION
This study demonstrates a social psychological impact of fibrous dysplasia on adults, in those with and without craniofacial involvement and with mild and severe forms of the disease. Clinical treatment should encompass assessment of quality of life issues and ensure access to psychosocial treatment resources for all fibrous dysplasia/McCune-Albright syndrome patients.
Topics: Adult; Humans; Female; Male; Quality of Life; Depression; Fibrous Dysplasia, Polyostotic; Anxiety; Pain
PubMed: 34730463
DOI: 10.1177/17423953211049436 -
International Journal of Ophthalmology 2022To report on the clinical features, surgical outcomes and gene mutation analysis of three ectodermal dysplasia probands with ocular diseases.
AIM
To report on the clinical features, surgical outcomes and gene mutation analysis of three ectodermal dysplasia probands with ocular diseases.
METHODS
A case-note review of three unrelated probands diagnosing with ectodermal dysplasia with ocular diseases was undertaken. Patient clinical features and the outcomes of surgery were analysed. The suspected pathogenic genes were analysed by whole exome sequencing from patients with ectodermal dysplasia and Sanger sequencing from family members.
RESULTS
The ocular clinical features of ectodermal dysplasia with ocular diseases mainly include eyelid ectropion, lagophthalmos and absence of lacrimal punctum. All the probands underwent surgeries of full-thickness free skin flap grafting to correct ectropion. They achieved good recovery, and there were no obvious complications during the follow-up. The gene sequencing results did not show any meaningful genetic mutations.
CONCLUSION
Lid ectropion is one of the key clinical traits of ectodermal dysplasia with ocular diseases. Ectropion correction with full-thickness free skin flap grafting is an effective procedure to correct ectropion for ectodermal dysplasia patients with ichthyosis-like tissue. The suspected pathogenic genes of ectodermal dysplasia with ectropion should be further verified or confirmed by large samples of the family.
PubMed: 35919316
DOI: 10.18240/ijo.2022.07.04 -
Clinical Endoscopy Jul 2021Proximal colorectal cancers (CRCs) account for up to half of CRCs. Sessile serrated lesions (SSLs) are precursors to CRC. Proximal location and presence of dysplasia in...
BACKGROUND/AIMS
Proximal colorectal cancers (CRCs) account for up to half of CRCs. Sessile serrated lesions (SSLs) are precursors to CRC. Proximal location and presence of dysplasia in SSLs predict higher risks of progression to cancer. The prevalence of dysplasia in proximal SSLs (pSSLs) and clinical characteristics of dysplastic pSSLs are not well studied.
METHODS
Endoscopically resected colonic polyps at our center between January 2016 and December 2017 were screened for pSSLs. Data of patients with at least one pSSL were retrieved and clinicopathological features of pSSLs were analysed. pSSLs with and without dysplasia were compared for associations.
RESULTS
Ninety pSSLs were identified, 45 of which had dysplasia giving a prevalence of 50.0%. Older age (65.9 years vs. 60.1 years, p=0.034) was associated with the presence of dysplasia. Twelve pSSLs were 10 mm or larger. After adjusting for age, pSSLs ≥10 mm had an adjusted odds ratio of 5.98 (95% confidence interval, 1.21-29.6) of having dysplasia compared with smaller pSSLs.
CONCLUSION
In our cohort of pSSLs, the prevalence of dysplasia is high at 50.0% and is associated with lesion size ≥10 mm. Endoscopic resection for all proximal serrated lesions should be en-bloc to facilitate accurate histopathological examination for dysplasia as its presence warrants shorter surveillance intervals.
PubMed: 33915614
DOI: 10.5946/ce.2020.198 -
Clinical Gastroenterology and... Jan 2020Endoscopic eradication therapy (EET) for Barrett's esophagus (BE) has unclear effects on the gastric cardia. We investigated the prevalence of intestinal metaplasia (IM)...
BACKGROUND & AIMS
Endoscopic eradication therapy (EET) for Barrett's esophagus (BE) has unclear effects on the gastric cardia. We investigated the prevalence of intestinal metaplasia (IM) and dysplasia in the cardia after complete eradication of IM (CEIM) and the incidence of newly diagnosed cardia IM or dysplasia after EET.
METHODS
We performed a prospective study, from 2013 through 2016, of patients with previously successful EET undergoing surveillance after CEIM (cross-sectional group) and treatment-naïve patients with BE undergoing EET (longitudinal group). Standard biopsies were collected from multiple levels in the cardia and analyzed histologically. We calculated the prevalence (cross-sectional group) and the incidence (longitudinal group) of cardia IM or dysplasia after EET.
RESULTS
Of the 116 patients in the cross-sectional group, 17 (15%) had cardia IM or dysplasia after CEIM: 12 patients had IM, 2 patients were indefinite for dysplasia, and 3 patients had low-grade dysplasia. Cardia IM or dysplasia were most commonly found at the tops of gastric folds. Among 42 subjects in the longitudinal group, the pre-treatment prevalence of cardia IM or dysplasia was 28.5% (3 with non-dysplastic IM, 9 with dysplastic IM, 1 indefinite for dysplasia, 2 with low-grade dysplasia, 3 with high-grade dysplasia, and 3 with intramucosal cancer). All achieved CEIM. The incidence of cardia IM or dysplasia was 11.9% after 18 months of follow up. IM or dysplasia was more higher in the cardia after CEIM than in the tubular esophagus (P < .01).
CONCLUSIONS
In a prospective study, we found that cardia dysplasia becomes less, not more, common, after successful EET; recurrence of IM or dysplasia was more frequent in the cardia than the esophagus. Patients with BE undergoing EET should have careful examination of the cardia, with a single set of surveillance biopsies at the top of the gastric folds.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biopsy; Cardia; Esophagus; Female; Gastroscopy; Humans; Incidence; Male; Metaplasia; Middle Aged; Neoplasm Recurrence, Local; Population Surveillance; Prevalence; Prospective Studies; Recurrence; Stomach; Stomach Neoplasms
PubMed: 31077822
DOI: 10.1016/j.cgh.2019.04.065