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Indian Journal of Ophthalmology Apr 2023Stüve-Wiedemann syndrome is a rare bone dysplasia with dysautonomic manifestations. Most patients die in the neonatal period or during infancy because of the multiple...
Stüve-Wiedemann syndrome is a rare bone dysplasia with dysautonomic manifestations. Most patients die in the neonatal period or during infancy because of the multiple complications they present. The main ophthalmological complications reported are reduced corneal reflex, corneal anesthesia, hypolacrimation, and severely reduced blinking. We are going to present the first tarsoconjunctival flap in a Stüve-Wiedemann patient, the surgery, and the results in a 13-year-old patient that came to our hospital because of severe corneal ulceration.
Topics: Infant, Newborn; Humans; Adolescent; Exostoses, Multiple Hereditary; Osteochondrodysplasias; Keratitis; Corneal Ulcer; Corneal Dystrophies, Hereditary
PubMed: 37026318
DOI: 10.4103/IJO.IJO_3260_22 -
Orthopaedics & Traumatology, Surgery &... Sep 2023In patients who have hereditary multiple osteochondroma (HMO), progressive deformity of the forearm skeleton may lead to radial head dislocation. The latter is...
INTRODUCTION
In patients who have hereditary multiple osteochondroma (HMO), progressive deformity of the forearm skeleton may lead to radial head dislocation. The latter is permanent, painful and causes weakness.
HYPOTHESIS
There is a relationship between the amount of ulnar deformity and the presence of radial head dislocation in patients with HMO.
MATERIALS AND METHODS
This was a cross-sectional radiographic study comprising an analysis of anterior-posterior (AP) and lateral x-rays of 110 forearms in children having a mean age of 8 years and 4 months who were followed for HMO between 1961 and 2014. Four factors reflecting on the ulnar deformity in the coronal plane were investigated on the AP view and three factors in the sagittal plane were investigated on the lateral view to identify any relationship between ulnar deformity and radial head dislocation. The forearms were separated into two groups: with radial head dislocation (26 cases) and without radial head dislocation (84 cases).
RESULTS
Ulnar bowing, intramedullary angle of ulnar bowing, tangent ulnar angle and overall ulnar angle were significantly higher in the group of children who had a radial head dislocation (0.05 vs 0.03, p<.001; 161 vs 167, p<001; 156 vs 162, p<001; 50 vs 30, p<.001) in univariate and multivariate analyses.
DISCUSSION
Ulnar deformity, evaluated using the method described here, is more often associated with radial head dislocation than other previously published radiological parameters. This provides new insight on this phenomenon and may help to determine which factors are associated with radial head dislocation and how to prevent it.
CONCLUSION
Ulnar bowing in the context of HMO, especially when evaluated on AP radiographs, is significantly associated with radial head dislocation.
LEVEL OF EVIDENCE
III; case-control study.
Topics: Child; Humans; Radius; Exostoses, Multiple Hereditary; Case-Control Studies; Cross-Sectional Studies; Retrospective Studies; Ulna; Joint Dislocations
PubMed: 36905956
DOI: 10.1016/j.otsr.2023.103591 -
American Journal of Medical Genetics.... Jun 2023Hereditary multiple exostoses (HME), also known as hereditary multiple osteochondroma (HMO), is an autosomal dominant disorder caused by pathogenic variants in...
Hereditary multiple exostoses (HME), also known as hereditary multiple osteochondroma (HMO), is an autosomal dominant disorder caused by pathogenic variants in exostosin-1 or -2 (EXT1 or EXT2). It is characterized by the formation of multiple benign growing osteochondromas (exostoses) that most commonly affect the long bones; however, it may also occur throughout the body. Although many of these lesions are clinically asymptomatic, some can lead to chronic pain and skeletal deformities and interfere with adjacent neurovascular structures. Here, we report two unrelated probands that presented with a clinical and molecular diagnosis of HME with venous malformation, a clinical feature not previously reported in individuals with HME.
Topics: Humans; Exostoses, Multiple Hereditary; N-Acetylglucosaminyltransferases; Mutation
PubMed: 36869625
DOI: 10.1002/ajmg.a.63158 -
The Turkish Journal of Pediatrics 2023Tricho-rhino-phalangeal syndrome (TRPS) is a rare, autosomal dominant disorder characterized by typical craniofacial features, ectodermal and skeletal findings. TRPS...
BACKGROUND
Tricho-rhino-phalangeal syndrome (TRPS) is a rare, autosomal dominant disorder characterized by typical craniofacial features, ectodermal and skeletal findings. TRPS type 1 (TRPS1) is caused by pathogenic variations in the TRPS1 gene, which relates to the vast majority of cases. TRPS type 2 (TRPS2) is a contiguous gene deletion syndrome involving loss of functional copies of the TRPS1, RAD21, and EXT1. Herein, we reported the clinical and genetic spectrum of seven TRPS patients with a novel variant. We also reviewed the musculoskeletal and radiological findings in the literature.
METHODS
Seven Turkish patients (three female, four male) from five unrelated families aged between 7 to 48 years were evaluated. The clinical diagnosis was confirmed by either molecular karyotyping or TRPS1 sequencing analysis via next-generation sequencing.
RESULTS
Both TRPS1 and TRPS2 patients had some common distinctive facial features and skeletal findings. All patients had a bulbous nose with hypoplastic alae nasi, brachydactyly, short metacarpals and phalanges in variable stages. Low bone mineral density (BMD) was identified in two TRPS2 family members presenting with bone fracture, and growth hormone deficiency was detected in two patients. Skeletal X-ray imaging revealed cone-shaped epiphysis of the phalanges in all, and multiple exostoses were present in three patients. Cerebral hamartoma, menometrorrhagia and long bone cysts were among the new/rare conditions. Three pathogenic variants in TRPS1 were identified in four patients from three families, including a frameshift (c.2445dup, p.Ser816GlufsTer28), one missense (c.2762G > A), and a novel splice site variant (c.2700+3A > G). We also reported a familial inheritance in TRPS2 which is known to be very rare.
CONCLUSIONS
Our study contributes to the clinical and genetic spectrum of patients with TRPS while also providing a review by comparing with previous cohort studies.
Topics: Adolescent; Adult; Child; Female; Humans; Male; Middle Aged; Young Adult; Langer-Giedion Syndrome; Repressor Proteins; Syndrome
PubMed: 36866988
DOI: 10.24953/turkjped.2022.793 -
International Orthopaedics May 2023
Comment on the article: Distraction osteogenesis at the proximal third of the ulna for the treatment of Masada type I/IIb deformities in children with hereditary multiple exostoses: a retrospective review of twenty cases.
Topics: Child; Humans; Osteogenesis, Distraction; Retrospective Studies; Exostoses, Multiple Hereditary; Ulna; Forearm
PubMed: 36847801
DOI: 10.1007/s00264-023-05733-w -
Biology Jan 2023Low density lipoprotein receptor-related protein 4 (LRP4; MIM 604270) modulates WNT/β-catenin signaling, through its binding of WNT ligands, and to co-receptors LRP5/6,...
BACKGROUND
Low density lipoprotein receptor-related protein 4 (LRP4; MIM 604270) modulates WNT/β-catenin signaling, through its binding of WNT ligands, and to co-receptors LRP5/6, and WNT inhibitors DKK1, SOSTDC1, and SOST. LRP4 binds to SOSTDC1 and WNT proteins establishing a negative feedback loop between Wnt/β-catenin, Bmp, and Shh signaling during the bud and cap stages of tooth development. Consistent with a critical role for this complex in developing teeth, mice lacking or have multiple dental anomalies including supernumerary incisors and molars. However, there is limited evidence supporting variants in in human dental pathologies.
METHODS
We clinically, radiographically, and molecularly investigated 94 Thai patients with mesiodens. mutant mice were generated in order to study the effects of aberrant expression in mice.
RESULTS
Whole exome and Sanger sequencing identified three extremely rare variants (c.4154A>G, p.Asn1385Ser; c.3940G>A, p.Gly1314Ser; and c.448G>A, p.Asp150Asn) in in seven patients with mesiodens. Two patients had oral exostoses and two patients had root maldevelopments. Supernumerary incisors were observed in mutant mice.
CONCLUSIONS
Our study implicates heterozygous genetic variants in as contributing factors in the presentation of mesiodens, root maldevelopments, and oral exostoses, possibly as a result of altered WNT/β-catenin-BMP-SHH signaling.
PubMed: 36829498
DOI: 10.3390/biology12020220 -
Journal of Pediatric OrthopedicsThe Pediatric Outcomes Data Collection Instrument (PODCI) is a validated quality-of-life questionnaire with 6 domains designed to provide a standardized method of...
BACKGROUND
The Pediatric Outcomes Data Collection Instrument (PODCI) is a validated quality-of-life questionnaire with 6 domains designed to provide a standardized method of measuring outcomes in pediatric musculoskeletal conditions. To our knowledge there are no reports on its use in children with multiple hereditary exostosis (MHE).
QUESTIONS/PURPOSES
Most published studies on MHE patients have described the efficacy of specific surgical techniques or the specification of deformities. Little is known about the general health status of pediatric patients, the severity of pain, loss of function, and how MHE influences the activities of daily life. We aim to assess the functional levels of MHE pediatric patients with PODCI questionnaire.
PATIENTS AND METHODS
As a cross-sectional study, we prospectively administered PODCI to 34 pediatric patients diagnosed with MHE and their families. The score distributions were compared with values published earlier for children and adolescents without musculoskeletal disorders using the Student and Welch t tests. Parents and adolescents' reports were compared using Wilcoxon signed rank test. Physical examination and PODCI score relation were evaluated by Spearman test.
RESULTS
Children with MHE have significantly lower scores ( P <0,05) in comparison with unaffected children in all domains using the Student and Welch t test. Parents score differs from children score with statistically relevance in pain and comfort domain ( P <0,5). The Spearman test showed a negative correlation between physical examination and PODCI score with statistical significance.
CONCLUSIONS
These results point towards PODCI's capacity in evaluating functional outcomes of pediatric patients with MHE.
LEVEL OF EVIDENCE
Diagnostic Study, Level III.
Topics: Adolescent; Child; Humans; Exostoses, Multiple Hereditary; Cross-Sectional Studies; Outcome Assessment, Health Care; Musculoskeletal Diseases; Surveys and Questionnaires; Pain
PubMed: 36806113
DOI: 10.1097/BPO.0000000000002372 -
International Orthopaedics May 2023
Response to Jacques Caton, MD's comments on the article "Distraction osteogenesis at the proximal third of the ulna for the treatment of Masada type I/IIb deformities in children with hereditary multiple exostoses: a retrospective review of twenty cases" by Lu et al.
Topics: Child; Humans; Osteogenesis, Distraction; Retrospective Studies; Exostoses, Multiple Hereditary; Ulna; Forearm
PubMed: 36799972
DOI: 10.1007/s00264-023-05732-x -
Heliyon Jan 2023Our previous study in genetic mouse models found that NFATc1 and NFATc2 suppress osteochondroma formation from entheseal progenitors. However, it remains unclear whether...
BACKGROUND
Our previous study in genetic mouse models found that NFATc1 and NFATc2 suppress osteochondroma formation from entheseal progenitors. However, it remains unclear whether NFAT signaling is also involved in human osteochondromagenesis. As the first step in addressing this question, the current study aimed to determine the expression patterns of NFATC1 and NFATC2 in human osteochondroma samples.
METHODS
Immunohistochemistry (IHC) was used to examine and analyze NFATC1 and NFATC2 expression in human osteochondroma samples. The human periosteum was used to map the expression of NFATC1 under physiological conditions by IHC. Furthermore, human periosteal progenitors were isolated and identified from the periosteal tissues of bone fracture healing patients. The expression of NFATC1 in human periosteal progenitors was characterized by Western blotting compared to human bone marrow stromal cells (BMSC).
RESULTS
The IHC results showed that the expression of NFATC1 was undetectable in most human osteochondromas cells, and only a small proportion of osteochondroma cells, especially clonally grown chondrocytes, showed positive staining of NFATC1. NFATC2 expression was also undetectable in most chondrocytes in human osteochondromas. The mouse and human periosteum showed a comparable ratio of NFATC1 positive cells (9.56 ± 0.80% 11.04 ± 2.05%, = 0.3101). Furthermore, Western blotting analysis revealed that NFATC1 expression was highly enriched in human periosteal progenitors compared to BMSC.
CONCLUSIONS
NFATC1 and NFATC2 are undetectable in most human osteochondroma chondrocytes. The expression pattern of NFATC1 in human osteochondromas and the normal periosteum suggests that NFAT signaling could be suppressed during human osteochondromagenesis.
PubMed: 36747924
DOI: 10.1016/j.heliyon.2023.e13018 -
Medicina (Kaunas, Lithuania) Dec 2022: Hereditary multiple exostoses (HME) is a disease characterized by cartilage-capped bony protuberances at the site of growth plates of long bones. Functional mutations...
: Hereditary multiple exostoses (HME) is a disease characterized by cartilage-capped bony protuberances at the site of growth plates of long bones. Functional mutations in the exostosin genes ( and ) are reported to affect the hedgehog signalling pathways leading to multiple enchondromatosis. However, the exact role of each EXT protein in the regulation of heparan sulphate (HS) chain elongation is still an enigma. In this study, a Pakistani family with HME is investigated to find out the genetic basis of the disease. : Genotyping of eight members of the family by amplifying microsatellite markers, tightly linked to the and genes. : The study revealed linkage of the HME family to the locus 8q24.1. Sanger sequencing identified a heterozygous deletion () in exon 1 of , segregating with the disease phenotype in the family. In silico analysis predicted a shift in the frame causing an early stop codon (p.R83GfsX52). The predicted dwarf protein constituting 134 amino acids was functionally aberrant with a complete loss of the catalytic domain at the C-terminus. Interestingly, an alternative open reading frame 3 (ORF3) caused by the frame shift is predicted to encode a protein sequence, identical to the wild type and containing the catalytic domain, but lacking the first 100 amino acids of the wild-type EXT1 protein. : Consequently, haploinsufficiency could be the cause of HME in the investigated family as the mutated copy of is ineffective for complex formation. The predicted ORF3 protein could be of great significance in understanding several aspects of HME pathogenesis.
Topics: Humans; Exostoses, Multiple Hereditary; Haploinsufficiency; Pakistan; Hedgehog Proteins; Mutation; N-Acetylglucosaminyltransferases; Heparitin Sulfate; Amino Acids
PubMed: 36676722
DOI: 10.3390/medicina59010100