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World Journal of Clinical Cases Jul 2023Congenital glaucoma associated with Roberts syndrome (RS) is an unusual and unique condition. No previous report describes this association. A multidisciplinary approach...
BACKGROUND
Congenital glaucoma associated with Roberts syndrome (RS) is an unusual and unique condition. No previous report describes this association. A multidisciplinary approach including molecular studies were conducted to reach the final diagnosis.
CASE SUMMARY
We present a rare case of a 1-wk-old male with RS associated with bilateral congenital glaucoma, left ectopic kidney, and left-hand rudimentary digits. A comprehensive approach was applied by which bilateral non-penetrating glaucoma surgery was performed with good control of intraocular pressure for more than 6 mo. Cytogenetic and molecular testing were conducted and revealed normal measurements.
CONCLUSION
This report described a case of a male baby with clinical features of RS but with a negative molecular analysis, presenting with left-hand rudimentary digits, bilateral congenital glaucoma, and left ectopic kidney. To the best of our knowledge, this is the first case reported with phocomelia, bilateral congenital glaucoma, and unilateral ectopic kidney.
PubMed: 37469722
DOI: 10.12998/wjcc.v11.i19.4635 -
Microorganisms Sep 2023Guanylate-binding proteins (GBPs) are highly expressed interferon-stimulated genes (ISGs) that play significant roles in protecting against invading pathogens. Although...
Guanylate-binding proteins (GBPs) are highly expressed interferon-stimulated genes (ISGs) that play significant roles in protecting against invading pathogens. Although their functions in response to RNA viruses have been extensively investigated, there is limited information available regarding their role in DNA viruses, particularly poxviruses. Ectromelia virus (ECTV), a member of the orthopoxvirus genus, is a large double-stranded DNA virus closely related to the monkeypox virus and variola virus. It has been intensively studied as a highly effective model virus. According to the study, GBP2 overexpression suppresses ECTV replication in a dose-dependent manner, while GBP2 knockdown promotes ECTV infection. Additionally, it was discovered that GBP2 primarily functions through its N-terminal GTPase activity, and the inhibitory effect of GBP2 was disrupted in the GTP-binding-impaired mutant GBP2. This study is the first to demonstrate the inhibitory effect of GBP2 on ECTV, and it offers insights into innovative antiviral strategies.
PubMed: 37764102
DOI: 10.3390/microorganisms11092258 -
Journal of Anatomy Jun 2024The etiology of sirenomelia is currently unknown. Data are limited in comparing external and internal abnormalities using modern imaging technologies and molecular...
The etiology of sirenomelia is currently unknown. Data are limited in comparing external and internal abnormalities using modern imaging technologies and molecular genetic analysis. The purpose of the current study was designed to compare external and internal anatomical defects in two cases of sirenomelia and Potter's sequence. Considered rare, Potter's sequence is a fetal disorder with characteristic features of bilateral renal agenesis, obstructive uropathy, atypical facial appearance, and limb malformations. The internal and external malformations of two term fetuses with sirenomelia and Potter's sequence were compared using assessment of external features, radiography and MRI on internal structures, and molecular genetic studies on sex determination. Data reveal that both fetuses were male and manifested with an overlapping but distinct spectrum of abnormalities. Principal differences were noted in the development of the ears, brain, urogenital system, lower limbs, pelvis, and vertebral column. Defects of the axial mesoderm are likely to underlie the abnormalities seen in both fetuses. The first one, which had only caudal defects, was found to have a spectrum of abnormalities most similar to those associated with more severe forms of the small pelvic outlet syndrome, although the structure and orientation of the sacrum and iliae were different from previously reported cases. The other had both caudal and cranial defects, and was most similar to those described in the axial mesodermal dysplasia syndrome. Defects associated with sirenomelia can be evaluated with standard gross anatomy examination, radiology, MRI, and modified PCR techniques to determine anatomical abnormalities and the sex of preserved specimens, respectively. Evidence indicated that sirenomelia could be developed via various etiologies.
Topics: Humans; Male; Ectromelia; Female; Magnetic Resonance Imaging; Abnormalities, Multiple; Pregnancy; Fetus
PubMed: 38267217
DOI: 10.1111/joa.14015 -
JPRAS Open Sep 2023We present a case describing a technique for the surgical management and aesthetico-functional reconstruction of a shoulder in an adult with unilateral upper limb...
We present a case describing a technique for the surgical management and aesthetico-functional reconstruction of a shoulder in an adult with unilateral upper limb phocomelia (ULP). A 25 year old male patient was presented to our clinic with upper left limb non-syndromic phocomelia. His main concerns was an aesthetically unpleasant limb and shoulder shape. Few older publications describe available options for pediatric patients, such as clavicle transposition or limb amputation, but nowadays ULP treatment options focus on prosthetic rehabilitation (PR) and targeted muscle reinnervation (TMR). Our patient refused any prosthesis, and TMR is expensive, requires an experienced rehabilitation team and has limited availability. We aim to describe a non-expensive, simple and effective option for selected adult patients with limited shoulder functionality wishes. We used the existent hypoplastic limb for shoulder mound reconstruction, providing the patient with a more anatomical shoulder shape. The palmar skin of the hypoplastic hand and three existing fingers were excised. Also, distal phalanges were amputated. Then, the hand was rotated and positioned under the coracoid process, creating a shoulder-like mound. there has been a loss of shoulder volume compared to early postoperative weeks, but the patient is satisfied with the results. Nevertheless, we found some limitations to our approach such as long-lasting postoperative pain, sensory symptomatology, and loss of volume of the reconstructed shoulder. Those could be solved with the complete denervation of the limb and a Latissimus Dorsi (LD) transposition flap in a second stage of reconstructive surgery.
PubMed: 37560485
DOI: 10.1016/j.jpra.2023.06.006 -
Journal of Pediatric Orthopedics Aug 2023Fibular hemimelia (FH) represents the most common deficiency of the long bones and is associated with multiple deformities. Reconstructive treatment with external...
BACKGROUND
Fibular hemimelia (FH) represents the most common deficiency of the long bones and is associated with multiple deformities. Reconstructive treatment with external fixators in FH restores normal lower extremity alignment and length with plantigrade feet for a balanced and effective gait. The aim of this study is to evaluate the outcomes of lower limb lengthening and simultaneous tri-plane deformity correction with a computer-assisted hexagonal external fixator in children with FH.
METHODS
A retrospective review was performed for FH cases treated with a computer-assisted hexagonal external fixator in a tertiary referral center. Leg length discrepancy (LLD), interphyseal angles, tibiocalcaneal distances, healing index (HI), and callus shapes were analyzed for radiologic evaluation, and the Pediatric Quality of Life Inventory (PedsQL) was used for functional assessment. Limbs with HI <50 days/cm, PedsQL >75, and without regenerate fractures were considered successful lengthenings.
RESULTS
Twenty-four limbs of 23 patients were included. The limbs were lengthened for a mean of 7.24 cm (range, 4.7 to 15.6). The initial LLD of 5.6 cm (range, 0.5 to 19 cm) increased to 1.7 cm (range, 0.1 to 6 cm), and the mean interphyseal angle was 12.7 degree (range, 1.5 to 54.2 degree), tibiocalcaneal distance was 0.85 cm (range, 0.1 to 1.7) at final follow-up. The most common regenerated bone morphology was cylindrical, as seen in 11 limbs (45.8%). The average PedsQL score was 83.5 (range, 69.5 to 96.7). Sixteen limbs (66.7%) had successful lengthening at their first, and 4 limbs (80%) had successful lengthening at their second surgeries. Seven limbs had complications requiring surgical intervention (29.1%), with 3 (12.5%) regenerate fractures after external fixators removal.
CONCLUSIONS
Limb reconstruction with computer-assisted hexapod fixators is a successful and reliable option for the treatment of LLD in FH, and patients demonstrate good functional outcomes. Surgeons should be aware of potential complications and should utilize prophylactic measures when necessary.
LEVELS OF EVIDENCE
Level III, retrospective comparative study.
Topics: Child; Humans; Ectromelia; Retrospective Studies; Quality of Life; Bone Lengthening; External Fixators; Leg Length Inequality; Lower Extremity; Fractures, Bone; Computers; Treatment Outcome; Tibia
PubMed: 37254033
DOI: 10.1097/BPO.0000000000002436 -
The Journal of Hand Surgery, European... Mar 2024We herein report on the application of a novel motorized prosthetic hand in a child with upper extremity phocomelia.
We herein report on the application of a novel motorized prosthetic hand in a child with upper extremity phocomelia.
Topics: Child; Humans; Ectromelia; Upper Extremity; Artificial Limbs; Upper Extremity Deformities, Congenital; Hand; Prosthesis Design
PubMed: 37882659
DOI: 10.1177/17531934231209645 -
JBJS Case Connector Oct 2023This is a case of a female patient born with thrombocytopenia-absent radius syndrome, with bilateral upper extremity phocomelia, bilateral hip dislocations, and...
CASE
This is a case of a female patient born with thrombocytopenia-absent radius syndrome, with bilateral upper extremity phocomelia, bilateral hip dislocations, and congenital fusion of the right knee with progressively worsening flexion contracture. At age 3 years and 5 months, the patient was treated with excision of the knee ankylosis and Van Nes rotationplasty. This proved durable at age 20 years (final follow-up) without any need for further surgery and without complication.
CONCLUSION
This is the first known report of Van Nes rotationplasty as a durable treatment option in the management of congenital knee ankylosis, which may avoid reoperation and eliminate risk of recurrence.
Topics: Humans; Female; Child, Preschool; Young Adult; Adult; Knee Joint; Osteotomy; Reoperation; Joint Diseases; Ankylosis
PubMed: 37831787
DOI: 10.2106/JBJS.CC.23.00303 -
BMC Veterinary Research Dec 2023Ectromelia virus (ECTV) is the causative agent of mousepox in mice. In the past century, ECTV was a serious threat to laboratory mouse colonies worldwide. Recombinase...
BACKGROUND
Ectromelia virus (ECTV) is the causative agent of mousepox in mice. In the past century, ECTV was a serious threat to laboratory mouse colonies worldwide. Recombinase polymerase amplification (RPA), which is widely used in virus detection, is an isothermal amplification method.
RESULTS
In this study, a probe-based RPA detection method was established for rapid and sensitive detection of ECTV.Primers were designed for the highly conserved region of the crmD gene, the main core protein of recessive poxvirus, and standard plasmids were constructed. The lowest detection limit of the ECTV RT- RPA assay was 100 copies of DNA mol-ecules per reaction. In addition, the method showed high specificity and did not cross-react with other common mouse viruses.Therefore, the practicability of the RPA method in the field was confirmed by the detection of 135 clinical samples. The real-time RPA assay was very similar to the ECTV real-time PCR assay, with 100% agreement.
CONCLUSIONS
In conclusion, this RPA assay offers a novel alternative for the simple, sensitive, and specific identification of ECTV, especially in low-resource settings.
Topics: Animals; Mice; Recombinases; Ectromelia virus; Sensitivity and Specificity; Nucleic Acid Amplification Techniques; Real-Time Polymerase Chain Reaction
PubMed: 38053140
DOI: 10.1186/s12917-023-03703-3 -
Hormone Research in Paediatrics 2024The thalidomide disaster resulted in tremendous congenital malformations in more than 10,000 children in the late 1950s and early 1960s. (Review)
Review
BACKGROUND
The thalidomide disaster resulted in tremendous congenital malformations in more than 10,000 children in the late 1950s and early 1960s.
SUMMARY
Although numerous putative mechanisms were proposed to explain thalidomide teratogenicity, it was confirmed only recently that thalidomide, rather its derivative 5-hydroxythalidomide (5HT) in a complex with the cereblon protein, interferes with early embryonic transcriptional regulation. 5HT induces selective degradation of SALL4, a principal transcriptional factor of early embryogenesis. Genetic syndromes caused by pathogenic variants of the SALL4 gene phenocopy thalidomide embryopathy with congenital malformations ranging from phocomelia, reduced radial ray, to defects of the heart, kidneys, ear, eye, and possibly cerebral midline and pituitary. SALL4 interacts with TBX5 and a handful of other transcriptional regulators and downregulates the Sonic hedgehog signaling pathway. Cranial midline defects, microcephaly, and short stature due to growth hormone deficiency have been occasionally reported in children carrying SALL4 pathogenic variants associated with generalized stunting of growth rather than just the loss of height attributable to the shortening of leg bones in many children with thalidomide embryopathy.
KEY MESSAGES
Thus, SALL4 joins the candidate gene list for monogenic syndromic pituitary insufficiency. In this review, we summarize the journey from the thalidomide disaster through the functions of the SALL4 gene to its link to the hormonal regulation of growth.
Topics: Humans; Abnormalities, Multiple; Fetal Diseases; Hedgehog Proteins; Thalidomide; Transcription Factors; Upper Extremity
PubMed: 37285827
DOI: 10.1159/000531452 -
International Journal of Molecular... Dec 2023Ectromelia virus (ECTV) is a causative agent of mousepox. It provides a suitable model for studying the immunobiology of orthopoxviruses, including their interaction...
Ectromelia virus (ECTV) is a causative agent of mousepox. It provides a suitable model for studying the immunobiology of orthopoxviruses, including their interaction with the host cell cytoskeleton. As professional antigen-presenting cells, dendritic cells (DCs) control the pericellular environment, capture antigens, and present them to T lymphocytes after migration to secondary lymphoid organs. Migration of immature DCs is possible due to the presence of specialized adhesion structures, such as podosomes or focal adhesions (FAs). Since assembly and disassembly of adhesive structures are highly associated with DCs' immunoregulatory and migratory functions, we evaluated how ECTV infection targets podosomes and FAs' organization and formation in natural-host bone marrow-derived DCs (BMDC). We found that ECTV induces a rapid dissolution of podosomes at the early stages of infection, accompanied by the development of larger and wider FAs than in uninfected control cells. At later stages of infection, FAs were predominantly observed in long cellular extensions, formed extensively by infected cells. Dissolution of podosomes in ECTV-infected BMDCs was not associated with maturation and increased 2D cell migration in a wound healing assay; however, accelerated transwell migration of ECTV-infected cells towards supernatants derived from LPS-conditioned BMDCs was observed. We suggest that ECTV-induced changes in the spatial organization of adhesive structures in DCs may alter the adhesiveness/migration of DCs during some conditions, e.g., inflammation.
Topics: Animals; Mice; Ectromelia virus; Ectromelia, Infectious; Adhesives; Adhesiveness; Dendritic Cells
PubMed: 38203729
DOI: 10.3390/ijms25010558