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Indian Dermatology Online Journal 2024Ectodermal dysplasias are a heterogeneous group of disorders that are characterized by abnormal development of ectodermal structures like hair, teeth, nails, and sweat... (Review)
Review
Ectodermal dysplasias are a heterogeneous group of disorders that are characterized by abnormal development of ectodermal structures like hair, teeth, nails, and sweat glands. Alhough they were earlier classified according to the structures affected and hence the clinical manifestations, recent developments inch towards a genetic basis for classification. They are currently divided into four groups of disorders based on the pathway involved, which includes the ectodysplasin/nuclear factor-kappa B (NFKB) pathway, wingless-type MMTV integration site family, member 10 ([wingless related integration site] WNT10), tumor protein p63 (TP63), and the structural group. In spite of attempts at the segregation of the various disorders, there is a great degree of overlap in clinical features among the conditions, which makes a thorough history-taking and clinical examination important in helping us arrive at a diagnosis and judge the various systems involved. A multidisciplinary approach forms the crux of the management of patients with ectodermal dysplasias and their families, with a focus on education, counseling, prosthesis, and an overall rehabilitative outlook. Special attention must also be paid to screening family members for varying severities of the disorders, and an attempt must be made at a genetic diagnosis with genetic counseling.
PubMed: 38845644
DOI: 10.4103/idoj.idoj_599_23 -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2022Actinic cheilitis is a potentially malignant lesion most commonly found in the lower lip of individuals with chronic exposure to ultraviolet radiation. The aim of this...
BACKGROUND
Actinic cheilitis is a potentially malignant lesion most commonly found in the lower lip of individuals with chronic exposure to ultraviolet radiation. The aim of this study was to develop and to test a clinical index that can be used to assess the severity of actinic cheilitis.
MATERIAL AND METHODS
The clinical index of actinic cheilitis was applied to 36 patients. An incisional biopsy was obtained to grade oral epithelial dysplasias following the World Health Organization (WHO) and binary systems, and to evaluate their association with clinical characteristics by Fisher's exact test (P<0.05). The accuracy of the index was evaluated based on sensitivity, specificity, positive and negative predictive values, and receiver operating curve.
RESULTS
The blurring between the border of the lip and the skin was significantly associated with cases without dysplasia/mild epithelial dysplasia (P=0.041) and with low risk of malignancy (P=0.005). Ulcers and crusts were significantly associated with moderate/severe epithelial dysplasia (P=0.002 and P=0.012, respectively) and high risk of malignancy (P=0.005 and P=0.045, respectively). Erosion showed a significant association only with high-risk cases of malignancy (P=0.024). The cut-off values of the diagnostic test showing the best performance were 10 for the WHO grading system and 11 for the binary system.
CONCLUSIONS
The index cut-offs with the highest accuracy were considered indicators for a biopsy. Erosion, ulceration and crusts were associated with more severe oral epithelial dysplasias.
Topics: Cheilitis; Humans; Hyperplasia; Lip; Lip Neoplasms; Ultraviolet Rays
PubMed: 35660729
DOI: 10.4317/medoral.25243 -
Der Hautarzt; Zeitschrift Fur... Feb 2021Human papillomavirus (HPV) infections belong to the most frequent viral infections. Besides benign common warts and benign and malignant lesions of the head and neck... (Review)
Review
Human papillomavirus (HPV) infections belong to the most frequent viral infections. Besides benign common warts and benign and malignant lesions of the head and neck area, HPV can induce anogenital dysplasias and cancers. Since the year 2007, effective and safe prophylactic HPV vaccines are licensed in Europe. To date, a bivalent (HPV16 and 18) and a nonavalent HPV vaccine (HPV6, 11, 16, 18, 31, 33, 45, 52, and 58) are commercially available in Germany. The German standing committee on vaccination (STIKO) currently recommends gender-neutral prophylactic HPV-vaccination between 9 and 14 years of age, with the possibility of catch-up vaccination until the age of 17 years. Besides a large proportion of HPV-induced anogenital dysplasias and carcinomas, the nonavalent HPV vaccine also prevents anogenital warts. Iatrogenically immunocompromised patients older than 17 years of age should also receive prophylactic HPV vaccination, preferrably by the age of 26 years. In case of already acquired HPV infection or existing HPV-induced lesions prophylactic vaccination does not lead to accelerated HPV elimination or clearance of lesions.
Topics: Adolescent; Adult; Condylomata Acuminata; Europe; Germany; Humans; Papillomavirus Infections; Papillomavirus Vaccines; Vaccination
PubMed: 33337514
DOI: 10.1007/s00105-020-04739-4 -
Pediatric Surgery International Sep 2022Caudal duplication syndrome (CDS) has rarely been reported. The purpose was to describe the characteristics and discuss possible pathogenesis of CDS by reviewing our... (Review)
Review
PURPOSE
Caudal duplication syndrome (CDS) has rarely been reported. The purpose was to describe the characteristics and discuss possible pathogenesis of CDS by reviewing our experience along with a comprehensive literature review.
METHODS
A total of 51 patients including 3 from our team and 48 from literature were selected in this study. General condition, clinical manifestations, type of anomalies, treatment and prognosis was analyzed and summarized.
RESULTS
Among the 51 patients were 30 females and 21 males, and age at first clinical visit was from birth to 39 years old. Except 12 patients, most of the patients had no troubling clinical manifestation. Physical examination showed that 30 patients had 1 perineum, 21 patients had 2 completely independent perineums. Degree of duplication varied; colon-rectum tubular, bladders and urethras, vaginas in females and penis shafts and glans in males were found to be the most common type of alimentary system and urogenital system duplication in this study with 24/51, 41/51, 10/30 and 16/21 patients, respectively. Anorectal malformation was calculated: 18 had 2 ARMs, 14 had 1 normal anus and 1 ARM on the other side, 12 had a normal anus, 5 had 2 normal anus, the remaining 2 patients had only 1 ARM. Spinal cord anomalies were showed as meningomyeloceles and lipomas in 13 and 3 patients. Vertebral anomalies of bifid, dysplasias, scoliosis, and hemivertebra were noticed in 28 patients and accessory dysplasia lower limbs were found in 10 patients. Prognosis showed 39 of the 51 patients had normal function in urination and defecation.
CONCLUSIONS
CDS is an extremely rare disease with uncertain pathogenesis. Colon-rectum tubular duplication with two ARMs, duplicated bladders and urethras, double vaginas in females and penis shafts and glans in males are the most common type. Long-term prognosis is good with multidisciplinary, individualized and staged surgical procedures.
Topics: Abnormalities, Multiple; Anal Canal; Female; Humans; Male; Penis; Rectum; Syndrome; Urethra
PubMed: 35780394
DOI: 10.1007/s00383-022-05159-2 -
Science Translational Medicine May 2021Achondroplasia is the most prevalent genetic form of dwarfism in humans and is caused by activating mutations in FGFR3 tyrosine kinase. The clinical need for a safe and...
Achondroplasia is the most prevalent genetic form of dwarfism in humans and is caused by activating mutations in FGFR3 tyrosine kinase. The clinical need for a safe and effective inhibitor of FGFR3 is unmet, leaving achondroplasia currently incurable. Here, we evaluated RBM-007, an RNA aptamer previously developed to neutralize the FGFR3 ligand FGF2, for its activity against FGFR3. In cultured rat chondrocytes or mouse embryonal tibia organ culture, RBM-007 rescued the proliferation arrest, degradation of cartilaginous extracellular matrix, premature senescence, and impaired hypertrophic differentiation induced by FGFR3 signaling. In cartilage xenografts derived from induced pluripotent stem cells from individuals with achondroplasia, RBM-007 rescued impaired chondrocyte differentiation and maturation. When delivered by subcutaneous injection, RBM-007 restored defective skeletal growth in a mouse model of achondroplasia. We thus demonstrate a ligand-trap concept of targeting the cartilage FGFR3 and delineate a potential therapeutic approach for achondroplasia and other FGFR3-related skeletal dysplasias.
Topics: Achondroplasia; Animals; Aptamers, Nucleotide; Bone Development; Cell Differentiation; Chondrocytes; Mice; Rats; Receptor, Fibroblast Growth Factor, Type 3
PubMed: 33952673
DOI: 10.1126/scitranslmed.aba4226 -
European Journal of Obstetrics,... May 2021Aim of this study was the evaluation of prevalence of HPV infection and resulting genital dysplasia to assess the necessity and reasonability of pap smears and HPV...
INTRODUCTION
Aim of this study was the evaluation of prevalence of HPV infection and resulting genital dysplasia to assess the necessity and reasonability of pap smears and HPV testing in transgender patients. HPV is the most common sexually transmitted infection and responsible for the majority of genital dysplasias and malignancies. However, few data exist about the prevalence of HPV and dysplasia in transgender people.
METHODS
This retrospective data analysis of prospectively collected data includes all patients seen in our specialized outpatient clinic for transgender people. Gynecologic exam, colposcopy, cellular swabs and HPV typing were carried out. Primary endpoint was the prevalence of HPV and genital dysplasias in transgender patients. Secondary endpoints were the subtypes of HPV, demographic data, sexual orientation and co-morbidities in these patients.
RESULTS
We investigated overall 98 patients whereof 53 were transwomen and 45 transmen. Of those, 10.2 % had positive HPV tests and 10.2 % dysplastic changes in the PAP and one case of invasive anal carcinoma (1.02 %). Comorbidities included recurrent urinary tract infections, psychologic comorbidies and other, possibly hormone replacement related conditions.
CONCLUSION
The results underline the necessity of a routine gynecological examination including PAP and/or HPV screening and vaccinating, respectively, no matter of sexual orientation or comorbidities. Monitoring the existent anatomy may prevent invasive carcinoma requiring more invasive therapies. Moreover, concomitant pathologies are present and require long-term care of these patients almost all using hormone therapy and carrying several specific risk factors. Transgender-focused guidelines to take into account these peculiarities are needed.
Topics: Colposcopy; Female; Humans; Male; Papillomaviridae; Papillomavirus Infections; Pregnancy; Retrospective Studies; Transgender Persons; Uterine Cervical Neoplasms; Vaginal Smears
PubMed: 33836363
DOI: 10.1016/j.ejogrb.2021.03.030 -
Pediatric Radiology Feb 2020Fetal magnetic resonance imaging (MRI) is obtained for prenatal diagnosis and prognostication of skeletal dysplasias; however, related literature is limited.
BACKGROUND
Fetal magnetic resonance imaging (MRI) is obtained for prenatal diagnosis and prognostication of skeletal dysplasias; however, related literature is limited.
OBJECTIVE
The purpose of this study was to define the utility of fetal MRI for skeletal dysplasias and to report MRI findings associated with specific diagnoses.
MATERIALS AND METHODS
This retrospective study was approved by the institutional review board; informed consent was waived. Women referred for suspected fetal skeletal dysplasia who underwent MRI between January 2003 and December 2018 were included. Definitive diagnoses were determined by genetic testing, autopsy, physical examination and/or postnatal/postmortem imaging. Fetal MRI examinations and reports were reviewed. Descriptive statistics were used to summarize imaging findings.
RESULTS
Eighty-nine women were referred for fetal MRI for possible skeletal dysplasia. Forty-three (48%) were determined to have a diagnosis other than skeletal dysplasia and nine were excluded for lack of specific skeletal dysplasia diagnosis. Thirty-seven cases of skeletal dysplasia with available fetal MRI and specific diagnosis were included for analysis. Diagnoses included achondrogenesis (n=2), achondroplasia (n=5), Boomerang dysplasia (n=1), campomelic dysplasia (n=2), Jeune syndrome (n=1), Kniest dysplasia (n=1), osteogenesis imperfecta (n=15) and thanatophoric dysplasia (n=10). A specific skeletal dysplasia diagnosis was mentioned in 17/37 (46%) of MRI imaging reports and correct for 14/17 (82%). MRI findings were reported for each specific skeletal dysplasia diagnosis.
CONCLUSION
Fetal MRI is a useful diagnostic tool for skeletal dyplasias and excluded the diagnosis in nearly half of referred pregnancies. In addition to providing fetal lung volumes, fetal MRI demonstrates findings of the brain in achondroplasia and thanatophoric dysplasia, of the spine in achondroplasia and achondrogenesis, of the calvarium in osteogenesis imperfecta and thanatophoric dysplasia, and of the cartilage in Kniest dysplasia.
Topics: Adolescent; Adult; Bone Diseases, Developmental; Bone and Bones; Female; Humans; Magnetic Resonance Imaging; Pregnancy; Prenatal Diagnosis; Reproducibility of Results; Young Adult
PubMed: 31776601
DOI: 10.1007/s00247-019-04537-8 -
Frontiers in Neuroscience 2020Focal cortical dysplasias (FCDs) are a group of malformations of cortical development that constitute a common cause of drug-resistant epilepsy, often subjected to... (Review)
Review
Focal cortical dysplasias (FCDs) are a group of malformations of cortical development that constitute a common cause of drug-resistant epilepsy, often subjected to neurosurgery, with a suboptimal long-term outcome. The past few years have witnessed a dramatic leap in our understanding of the molecular basis of FCD. This study aimed to provide an updated review on the genomic and epigenetic advances underlying FCD etiology, to understand a genotype-phenotype correlation and identify priorities to lead future translational research. A scoping review of the literature was conducted, according to previously described methods. A comprehensive search strategy was applied in PubMed, Embase, and Web of Science from inception to 07 May 2020. References were screened based on title and abstract, and posteriorly full-text articles were assessed for inclusion according to eligibility criteria. Studies with novel gene variants or epigenetic regulatory mechanisms in patients that underwent epilepsy surgery, with histopathological diagnosis of FCD type I or II according to Palmini's or the ILAE classification system, were included. Data were extracted and summarized for an overview of evidence. Of 1,156 candidate papers, 39 met the study criteria and were included in this review. The advent of next-generation sequencing enabled the detection in resected FCD tissue of low-level brain somatic mutations that occurred during embryonic corticogenesis. The mammalian target of rapamycin (mTOR) signaling pathway, involved in neuronal growth and migration, is the key player in the pathogenesis of FCD II. Somatic gain-of-function variants in and its activators as well as germline, somatic, and second-hit mosaic loss-of-function variants in its related repressors have been reported. However, the genetic background of FCD type I remains elusive, with a pleomorphic repertoire of genes affected. DNA methylation and microRNAs were the two epigenetic mechanisms that proved to have a functional role in FCD and may represent molecular biomarkers. Further research into the possible pathogenic causes of both FCD subtypes is required, incorporating single-cell DNA/RNA sequencing as well as methylome and proteomic analysis. The collected data call for an integrated clinicopathologic and molecular genetic diagnosis in current practice not only to improve diagnostic accuracy but also to guide the development of future targeted treatments.
PubMed: 33551717
DOI: 10.3389/fnins.2020.580357 -
Bone Feb 2023Dysosteosclerosis (DSS) refers to skeletal dysplasias that radiographically feature focal appendicular osteosclerosis with variable platyspondyly. Genetic heterogeneity...
Dysosteosclerosis (DSS) refers to skeletal dysplasias that radiographically feature focal appendicular osteosclerosis with variable platyspondyly. Genetic heterogeneity is increasingly reported for the DSS phenotype and now involves mutations of SLC29A3, TNFRSF11A, TCIRG1, LRRK1, and CSF1R. Typical radiological findings are widened radiolucent long bones with thin cortices yet dense irregular metaphyses, flattened vertebral bodies, dense ribs, and multiple fractures. However, the radiographic features of DSS evolve, and the metaphyseal and/or appendicular osteosclerosis variably fades with increasing patient age, likely due to some residual osteoclast function. Fractures are the principal presentation of DSS, and may even occur in infancy with SLC29A3-associated DSS. Cranial base sclerosis can lead to cranial nerve palsies such as optic atrophy, and may be the initial presentation, though not observed with SLC29A3-associated DSS. Gene-specific extra-skeletal features can be the main complication in some forms of DSS such as CSF1R- associated DSS. Further genetic heterogeneity is likely, especially for X-linked recessive DSS and cases currently with an unknown genetic defect. Distinguishing DSS can be challenging due to variable clinical and radiological features and an evolving phenotype. However, defining the DSS phenotype is important for predicting complications, prognosis, and instituting appropriate health surveillance and treatment.
Topics: Humans; Osteopetrosis; Osteosclerosis; Osteochondrodysplasias; Mutation; Vacuolar Proton-Translocating ATPases; Nucleoside Transport Proteins
PubMed: 36402365
DOI: 10.1016/j.bone.2022.116615 -
Advances in Experimental Medicine and... 2023Ectodermal dysplasias are a group of >200 clinically and congenitally heterogeneous disorders characterized by abnormal development in the ectodermal structures, such as...
INTRODUCTION
Ectodermal dysplasias are a group of >200 clinically and congenitally heterogeneous disorders characterized by abnormal development in the ectodermal structures, such as hair, nails, teeth, and sweat glands. We report here the clinical and molecular genetic analysis of five Greek families with different types of ectodermal dysplasia (ED).
SUBJECTS
The study involved 15 individuals from 5 Greek families that included 8 ED patients, 5 carriers of recessive X-linked or autosomal ED, and 2 healthy relatives. After genetic counseling, the parents signed an informed consent form before subsequent genetic testing.
METHODS
Genomic DNA was isolated from white blood cells of all studied individuals. The search for mutations was realized in patients' DNA samples using next-generation sequencing (NGS) gene panel, whole exome sequencing (WES), chromosomal microarray analysis (CMA), and multiplex ligation-dependent probe amplification (MLPA) technique.
RESULTS
The clinical diagnosis of common X-linked recessive hypohidrotic ectodermal dysplasia (HED) was suspected in five male patients with partial anodontia of baby and permanent teeth, hypohidrosis, and thin hair from three families. All HED patients were hemizygous for deletions in the EDA1 gene (Xq13.1): three related patients had a 20 bp deletion, one had a 19 bp deletion, and one had a 180 bp deletion. A female patient had the rare autosomal dominant syndrome of ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) caused by heterozygous missense mutation in the TP63 gene (3q28) that appeared de novo. Two siblings with hypotrichosis and hypodontia, a female and a male, had two pathogenic mutations in compound heterozygosity in the TSPEAR gene (21q22.3); therefore they presented with ectodermal dysplasia type 14 (ECTD14).
CONCLUSION
Clinical and molecular genetic analysis may set an accurate diagnosis of different types of ED. In the reported families, genetic diagnosis and genetic counselling assisted the parents to view their children's condition realistically and to cooperate with the specialists who will contribute to the best possible treatment for their children.
Topics: Child; Infant; Humans; Male; Female; Cleft Lip; Cleft Palate; Ectodermal Dysplasia; Mutation; Molecular Biology; Pedigree
PubMed: 37525042
DOI: 10.1007/978-3-031-31978-5_15