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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 -
Orphanet Journal of Rare Diseases May 2021The ectodermal dysplasias (EDs) constitute a group of disorders characterized by abnormalities in two or more ectodermal derivatives, including skin, hair, teeth, and...
PURPOSE
The ectodermal dysplasias (EDs) constitute a group of disorders characterized by abnormalities in two or more ectodermal derivatives, including skin, hair, teeth, and sweat glands. The purpose of the current study was to evaluate ocular manifestations in pediatric patients with ED.
METHODS
Retrospective case series including consecutive ED subjects who were treated in the ophthalmology department at the Children's Hospital of Philadelphia over a 12-year period (2009-2020). Main Outcome Measures were ocular and ocular adnexal abnormalities.
RESULTS
Thirty subjects were included: 20 males (67%), mean age of 4.5 years (range 0.3-18). Patients with different subtypes were included, with the hypohidrotic ED and ectrodactyly-ectodermal dysplasia-clefting variants being most prevalent. Most common findings were: lacrimal drainage obstruction in 12 (40%) including punctal agenesis in 10 (33%), refractive errors in 13 (43%) and amblyopia in 6 (20%). A new finding of eyelid ptosis or eyelash ptosis was demonstrated in 11 subjects (37%), mostly associated with TP63 or EDA1 genes variants.
CONCLUSION
Ectodermal dysplasias are associated with various ocular pathologies and amblyopia in the pediatric population. We report a possible genetic association between lash ptosis and EDA1 gene, and eyelid ptosis and TP63 or EDA1 genes variants.
Topics: Adolescent; Child; Child, Preschool; Cleft Lip; Ectodermal Dysplasia; Humans; Infant; Limb Deformities, Congenital; Male; Retrospective Studies; Syndrome
PubMed: 33933124
DOI: 10.1186/s13023-021-01824-2 -
Developmental Dynamics : An Official... Mar 2021For the vast majority of the 6000 known rare disease the pathogenic mechanisms are poorly defined and there is little treatment, leading to poor quality of life and high... (Review)
Review
For the vast majority of the 6000 known rare disease the pathogenic mechanisms are poorly defined and there is little treatment, leading to poor quality of life and high healthcare costs. Genetic skeletal diseases (skeletal dysplasias) are archetypal examples of rare diseases that are chronically debilitating, often life-threatening and for which no treatments are currently available. There are more than 450 unique phenotypes that, although individually rare, have an overall prevalence of at least 1 per 4000 children. Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous disorder characterized by disproportionate short stature, joint pain, and early-onset osteoarthritis. MED is caused by mutations in the genes encoding important cartilage extracellular matrix proteins, enzymes, and transporter proteins. Recently, through the use of various cell and mouse models, disease mechanisms underlying this diverse phenotypic spectrum are starting to be elucidated. For example, ER stress induced as a consequence of retained misfolded mutant proteins has emerged as a unifying disease mechanisms for several forms of MED in particular and skeletal dysplasia in general. Moreover, targeting ER stress through drug repurposing has become an attractive therapeutic avenue.
Topics: Endoplasmic Reticulum Stress; Extracellular Matrix Proteins; Humans; Mutation; Osteochondrodysplasias; Quality of Life
PubMed: 32633442
DOI: 10.1002/dvdy.221 -
Human Mutation Jul 2022Different pathogenic variants in the fibrillin-1 gene (FBN1) cause Marfan syndrome and acromelic dysplasias. Whereas the musculoskeletal features of Marfan syndrome... (Review)
Review
Different pathogenic variants in the fibrillin-1 gene (FBN1) cause Marfan syndrome and acromelic dysplasias. Whereas the musculoskeletal features of Marfan syndrome involve tall stature, arachnodactyly, joint hypermobility, and muscle hypoplasia, acromelic dysplasia patients present with short stature, brachydactyly, stiff joints, and hypermuscularity. Similarly, pathogenic variants in the fibrillin-2 gene (FBN2) cause either a Marfanoid congenital contractural arachnodactyly or a FBN2-related acromelic dysplasia that most prominently presents with brachydactyly. The phenotypic and molecular resemblances between both the FBN1 and FBN2-related disorders suggest that reciprocal pathomechanistic lessons can be learned. In this review, we provide an updated overview and comparison of the phenotypic and mutational spectra of both the "tall" and "short" fibrillinopathies. The future parallel functional study of both FBN1/2-related disorders will reveal new insights into how pathogenic fibrillin variants differently affect the fibrillin microfibril network and/or growth factor homeostasis in clinically opposite syndromes. This knowledge may eventually be translated into new therapeutic approaches by targeting or modulating the fibrillin microfibril network and/or the signaling pathways under its control.
Topics: Brachydactyly; Fibrillin-1; Fibrillin-2; Humans; Marfan Syndrome; Musculoskeletal Abnormalities; Phenotype
PubMed: 35419902
DOI: 10.1002/humu.24383 -
Clinical Oral Investigations Oct 2023Skeletal dysplasia (SD) comprises more than 450 separate disorders. We hypothesized that their dental features would be distinctive and investigated the tooth...
OBJECTIVE
Skeletal dysplasia (SD) comprises more than 450 separate disorders. We hypothesized that their dental features would be distinctive and investigated the tooth characteristics of four patients with different SDs.
MATERIAL AND METHODS
Four SD patients with molecularly confirmed diagnoses, Pt-1 acromicric dysplasia, Pt-2 hypophosphatasia and hypochondroplasia, Pt-3 cleidocranial dysplasia, and Pt-4 achondroplasia, were recruited. A tooth from each patient was evaluated for mineral density (micro-computerized tomography), surface roughness (surface profilometer), microhardness, mineral contents (energy-dispersive X-ray), and ultrastructure (scanning electron microscopy and histology), and compared with three tooth-type matched controls.
RESULTS
Pt-1 and Pt-3 had several unerupted teeth. Pt-2 had an intact-root-exfoliated tooth at 2 years old. The lingual surfaces of the patients' teeth were significantly smoother, while their buccal surfaces were rougher, than controls, except for Pt-1's buccal surface. The patients' teeth exhibited deep grooves around the enamel prisms and rough intertubular dentin. Pt-3 demonstrated a flat dentinoenamel junction and Pt-2 had an enlarged pulp, barely detectable cementum layer, and ill-defined cemento-dentinal junction. Reduced microhardnesses in enamel, dentin, and both layers were observed in Pt-3, Pt-4, and Pt-1, respectively. Pt-1 showed reduced Ca/P ratio in dentin, while both enamel and dentin of Pt-2 and Pt-3 showed reduced Ca/P ratio.
CONCLUSION
Each SD has distinctive dental characteristics with changes in surface roughness, ultrastructure, and mineral composition of dental hard tissues.
CLINICAL RELEVANCE
In this era of precision dentistry, identifying the specific potential dental problems for each patient with SD would help personalize dental management guidelines.
PubMed: 37548766
DOI: 10.1007/s00784-023-05194-w -
Der Internist May 2021Delineating the genetic background and the underlying pathophysiology of rare skeletal dysplasias enables a broader understanding of these disorders as well as novel... (Review)
Review
Delineating the genetic background and the underlying pathophysiology of rare skeletal dysplasias enables a broader understanding of these disorders as well as novel perspectives regarding differential diagnosis and targeted development of therapeutic approaches. Hypophosphatasia (HPP) due to genetically determined Alkaline Phosphatase deficiency exemplifies this development. While an enzyme replacement therapy could be established for severe HPP with the prevailing bone manifestation, the clinical impact of not immediately bone-related manifestations just being successively understood. Correspondingly, the elucidation of the pathophysiology underlying renal phosphate wasting expanded our knowledge regarding phosphate metabolism and bone health and facilitated the development of an anti-FGF-23 Antibody for targeted treatment of X‑linked Hypophosphatemia (XLH). Evolutions regarding the nosology of osteogenesis imperfecta (OI) along with the identification of further causative genes also detected in the context of genetically determined osteoporosis illustrate the pathophysiologic interrelation between monogenetic bone dysplasias and multifactorial osteoporosis. While current therapeutic strategies for OI follow osteoporosis treatment, the expanding knowledge about OI forms the fundament for establishing improved treatment strategies-for both OI and osteoporosis. Similar developments are emerging regarding rare skeletal disorders like Achondroplasia, Fibrodysplasia ossificans progressive and Morbus Morquio (Mukopolysaccharidosis Type IV).
Topics: Bone and Bones; Fibroblast Growth Factor-23; Humans; Hypophosphatasia; Osteogenesis Imperfecta; Osteoporosis; Rare Diseases
PubMed: 33779789
DOI: 10.1007/s00108-021-00995-1 -
Asian Pacific Journal of Cancer... Sep 2020to investigate CD133 immunoexpression, cancer stem cells marker, in oral epithelial dysplasias (OEDs) and oral squamous cells carcinomas (OSCCs) and understandits...
OBJECTIVE
to investigate CD133 immunoexpression, cancer stem cells marker, in oral epithelial dysplasias (OEDs) and oral squamous cells carcinomas (OSCCs) and understandits possible involvement in the malignant transformation process of these lesions and to better elucidate their biological behavior.
MATERIAL AND METHODS
Tissue samples of 15 cases of OSCCs and 15 OEDs were subjected to CD133 antibody immunohistochemistry reactions. The analysis used quantitative parameters (number of immunostained cells regardless of immunostaining sublocations).
RESULTS
All samples of OSCCs and OEDs showed positive immunostaining, with no significant difference between these groups (p = 0.283). We did not observe statistical difference between the degree of dysplasia and the amount of CD133+ cells (p = 0.899). CD133 immunoexpression showed no association with the OEDs and OSCCs sites. It was observed that nuclear and cytoplasmic immunostaining was more evident with the progression of the malignant process.
CONCLUSION
It is suggested that the CD133 cellular localization together with the histopathological criteria of OEDs classification can contribute to provide more concrete indications about the oral carcinogenesis process.
Topics: AC133 Antigen; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Focal Epithelial Hyperplasia; Follow-Up Studies; Humans; Male; Middle Aged; Mouth Neoplasms; Precancerous Conditions; Prognosis
PubMed: 32986345
DOI: 10.31557/APJCP.2020.21.9.2501 -
Current Medical Imaging 2021McCune-Albright Syndrome (MAS) is a genetic disorder with a triad of endocrine diseases, café-au-lait macules and fibrous dysplasias. Craniofacial fibrous dysplasia is... (Review)
Review
BACKGROUND
McCune-Albright Syndrome (MAS) is a genetic disorder with a triad of endocrine diseases, café-au-lait macules and fibrous dysplasias. Craniofacial fibrous dysplasia is a term that is used to describe the fibrous dysplasia, which was localized at the craniofacial skeleton and is common in MAS patients.
OBJECTIVE
The objective of this review is to determine the involvement frequency of cranial and facial bones in patients with MAS and CFD.
METHODS
Articles in PubMed was searched with the following details "(mccune[Title/Abstract] OR albright[Title/Abstract]) OR ("craniofacial fibrous dysplasia"[MeSH Terms] OR ("craniofacial"[ All Fields] AND "fibrous"[All Fields] AND "dysplasia"[All Fields]) OR "craniofacial fibrous dysplasia"[All Fields])". The articles in which the authors did not state the involved bones or did not add any radiographic images were excluded from the study.
RESULTS
26 cases in 25 articles met the inclusion criteria. Among the 26 cases and our case, sphenoid and frontal bones were involved in 17 cases, parietal and occipital bones were involved in 15 cases, mandible and ethmoid bone were involved in 14 cases, maxilla-zygoma-temporal and palate was involved in 13, 11, 6 and 3 cases, respectively. Palate was involved in cases where maxilla was also involved. Our case was the only case that was evaluated with CBCT.
CONCLUSION
Routine follow-ups are important since new CFDs can occur in different cranial or facial bones. 2D imaging techniques may not be able to demonstrate early CFDs; thus, an advanced imaging technique should be used after MAS diagnosis.
Topics: Craniofacial Fibrous Dysplasia; Facial Bones; Fibrous Dysplasia of Bone; Fibrous Dysplasia, Polyostotic; Humans; Sphenoid Bone
PubMed: 33297918
DOI: 10.2174/1573405616666201209102418 -
Leukemia & Lymphoma Mar 2023The Philadelphia-negative myeloproliferative neoplasms (MPNs)-essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF), are characterized by a...
The Philadelphia-negative myeloproliferative neoplasms (MPNs)-essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF), are characterized by a propensity for thrombotic events and variable risks for transformation to MF (for ET and PV) and acute leukemia. Leukocytosis, which serves a minor criterion for the diagnosis of MF, is present in a significant portion of patients with MPNs. The relation and impact of leukocytosis on disease course and outcomes of patients with MPNs has been studied in multiple, large retrospective and prospective studies. Despite this, the association of leukocytosis and thrombosis, fibrosis and leukemic transformation remains unclear. This article details the published investigations regarding the impact of leukocytosis in MPNs and explores the changing role of leukocytosis in disease prognostication as increasing emphasis is placed on molecular and genetic studies.
Topics: Humans; Leukocytosis; Retrospective Studies; Prospective Studies; Myeloproliferative Disorders; Polycythemia Vera; Thrombocythemia, Essential; Primary Myelofibrosis; Thrombosis; Leukemia, Myeloid, Acute
PubMed: 36519233
DOI: 10.1080/10428194.2022.2156794