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SAGE Open Medical Case Reports 2023The treatment of osteoarthritis in patients with phocomelia with total knee arthroplasty is challenging due to the unusual anatomy and severe deformities. The authors...
The treatment of osteoarthritis in patients with phocomelia with total knee arthroplasty is challenging due to the unusual anatomy and severe deformities. The authors present a case of phocomelia caused by thalidomide with end-stage osteoarthritis and grossly medialized patella. The patient was treated with a cemented constrained non-hinged prosthesis and patelloplasty. Six months later, the patient had complete relief of pain and was able to walk without walking assistance. To our knowledge, total knee replacement in a patient with phocomelia caused by thalidomide has not been described in literature.
PubMed: 36798679
DOI: 10.1177/2050313X231154635 -
Journal of Medical Genetics Sep 1993
Topics: Abnormalities, Multiple; Adolescent; Amenorrhea; Ectromelia; Female; Genes, Recessive; Humans; Pelvic Bones; Syndrome; Uterus
PubMed: 8411080
DOI: 10.1136/jmg.30.9.797-a -
Annals of the New York Academy of... Dec 2017Postaxial limb hypoplasia (PALH) is a group of nonhereditary diseases with congenital lower limb deficiency affecting the fibular ray, including fibular hemimelia,... (Review)
Review
Postaxial limb hypoplasia (PALH) is a group of nonhereditary diseases with congenital lower limb deficiency affecting the fibular ray, including fibular hemimelia, proximal femoral focal deficiency, and tarsal coalition. The etiology and the developmental biology of the anomaly are still not fully understood. Here, we review the previous classification systems, present the clinical features, and discuss the developmental biology of PALH.
Topics: Ectromelia; Fibula; Genetic Predisposition to Disease; Humans; Limb Deformities, Congenital; Musculoskeletal Development; Mutation; Signal Transduction
PubMed: 28990185
DOI: 10.1111/nyas.13440 -
Arthroplasty Today Apr 2021Phocomelia is a rare congenital birth defect marked by hypoplastic or markedly absent limbs. Developmental dysplasia of the hip (DDH) is a congenital disorder with a... (Review)
Review
Phocomelia is a rare congenital birth defect marked by hypoplastic or markedly absent limbs. Developmental dysplasia of the hip (DDH) is a congenital disorder with a failure of the native acetabulum to provide complete coverage over the femoral head. The secondary osteoarthritis that develops from DDH is technically challenging for orthopedic surgeons because of distorted anatomy. The present case describes the diagnosis of Crowe 3 DDH in a phocomelia patient with hyperflexion requirements who successfully underwent staged bilateral total hip arthroplasty via a direct anterior approach. It highlights the utility of preoperative computerized tomography and intraoperative computer navigation to assist in implant placement. Recognizing difficult arthroplasty cases in advance is imperative as these cases may require great expertise and more extensive surgical planning.
PubMed: 34095402
DOI: 10.1016/j.artd.2021.01.005 -
Viruses Aug 2017Taterapox virus (TATV), which was isolated from an African gerbil () in 1975, is the most closely related virus to variola; however, only the original report has...
Taterapox virus (TATV), which was isolated from an African gerbil () in 1975, is the most closely related virus to variola; however, only the original report has examined its virology. We have evaluated the tropism of TATV in vivo in small animals. We found that TATV does not infect , a species of African dormouse, but does induce seroconversion in the Mongolian gerbil () and in mice; however, in wild-type mice and gerbils, the virus produces an unapparent infection. Following intranasal and footpad inoculations with 1 × 10⁶ plaque forming units (PFU) of TATV, immunocompromised mice showed signs of disease but did not die; however, SCID mice were susceptible to intranasal and footpad infections with 100% mortality observed by Day 35 and Day 54, respectively. We show that death is unlikely to be a result of the virus mutating to have increased virulence and that SCID mice are capable of transmitting TATV to C57BL/6 and C57BL/6 animals; however, transmission did not occur from TATV inoculated wild-type or mice. Comparisons with ectromelia (the etiological agent of mousepox) suggest that TATV behaves differently both at the site of inoculation and in the immune response that it triggers.
Topics: Animals; Antiviral Agents; Disease Models, Animal; Ectromelia virus; Ectromelia, Infectious; Host Specificity; Mice; Mice, Inbred C57BL; Mice, SCID; Orthopoxvirus; Poxviridae Infections; STAT1 Transcription Factor; Viral Tropism
PubMed: 28763036
DOI: 10.3390/v9080203 -
Human Mutation Jun 2010Cohesin is responsible for sister chromatid cohesion, ensuring the correct chromosome segregation. Beyond this role, cohesin and regulatory cohesin genes seem to play a... (Review)
Review
Cohesin is responsible for sister chromatid cohesion, ensuring the correct chromosome segregation. Beyond this role, cohesin and regulatory cohesin genes seem to play a role in preserving genome stability and gene transcription regulation. DNA damage is thought to be a major culprit for many human diseases, including cancer. Our present knowledge of the molecular basis underlying genome instability is extremely limited. Mutations in cohesin genes cause human diseases such as Cornelia de Lange syndrome and Roberts syndrome/SC phocomelia, and all the cell lines derived from affected patients show genome instability. Cohesin mutations have also been identified in colorectal cancer. Here, we will discuss the human disorders caused by alterations of cohesin function, with emphasis on the emerging role of cohesin as a genome stability caretaker.
Topics: Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; De Lange Syndrome; Gene Expression Regulation; Genetic Predisposition to Disease; Genomic Instability; Humans; Mutation; Neoplasms; Signal Transduction; Cohesins
PubMed: 20513141
DOI: 10.1002/humu.21252 -
Ghana Medical Journal Mar 2021We report a case of spontaneous rare birth deformity. A case of Amelia and Phocomelia in a neonate. Amelia is a rare congenital disorder, even more so, is the combined...
UNLABELLED
We report a case of spontaneous rare birth deformity. A case of Amelia and Phocomelia in a neonate. Amelia is a rare congenital disorder, even more so, is the combined amelia and phocomelia in a neonate. True Phocomelia was defined as the total absence of the intermediate segments of the limb. With the hand or foot (normal, almost normal, or malformed), directly attached to the trunk. The common aetiological association with phocomelia is from the use of thalidomide and genetic inheritance, as an autosomal recessive trait, involving chromosome 8. Isolated amelia is not generally considered to be of genetic origin. We present a neonate delivered by a 28-years multipara in Liberia, in West Africa Sub-Region, with amelia involving the two upper limbs, right lower limb and a Phocomelia involving the left lower limb (absence of tibia and fibula and feet with three toes). Africa is the only continent not included in the International Clearinghouse for Birth Defects Surveillance and Research. It is hoped that case reports of congenital limb deformities from Africa, will contribute to the formation of a database for birth defects shortly.
FUNDING
None declared.
PubMed: 38322389
DOI: 10.4314/gmj.v55i1.11 -
Saudi Medical Journal Dec 2014To describe cases of sirenomelia and severe caudal regression syndrome (CRS), to report the prevalence of sirenomelia, and compare our findings with the literature.
OBJECTIVE
To describe cases of sirenomelia and severe caudal regression syndrome (CRS), to report the prevalence of sirenomelia, and compare our findings with the literature.
METHODS
Retrospective data was retrieved from the medical records of infants with the diagnosis of sirenomelia and CRS and their mothers from 1989 to 2010 (22 years) at the Security Forces Hospital, Riyadh, Saudi Arabia. A perinatologist, neonatologist, pediatric neurologist, and radiologist ascertained the diagnoses. The cases were identified as part of a study of neural tube defects during that period. A literature search was conducted using MEDLINE.
RESULTS
During the 22-year study period, the total number of deliveries was 124,933 out of whom, 4 patients with sirenomelia, and 2 patients with severe forms of CRS were identified. All the patients with sirenomelia had single umbilical artery, and none were the infant of a diabetic mother. One patient was a twin, and another was one of triplets. The 2 patients with CRS were sisters, their mother suffered from type II diabetes mellitus and morbid obesity on insulin, and neither of them had a single umbilical artery. Other associated anomalies with sirenomelia included an absent radius, thumb, and index finger in one patient, Potter's syndrome, abnormal ribs, microphthalmia, congenital heart disease, hypoplastic lungs, and diaphragmatic hernia.
CONCLUSION
The prevalence of sirenomelia (3.2 per 100,000) is high compared with the international prevalence of one per 100,000. Both cases of CRS were infants of type II diabetic mother with poor control, supporting the strong correlation of CRS and maternal diabetes.
Topics: Abnormalities, Multiple; Diabetes Mellitus, Type 2; Ectromelia; Female; Humans; Infant, Newborn; Male; Meningocele; Pregnancy; Pregnancy Complications; Prevalence; Retrospective Studies; Sacrococcygeal Region; Saudi Arabia
PubMed: 25551110
DOI: No ID Found -
G3 (Bethesda, Md.) Feb 2022Roberts syndrome (RBS) is a multispectrum developmental disorder characterized by severe limb, craniofacial, and organ abnormalities and often intellectual disabilities....
Roberts syndrome (RBS) is a multispectrum developmental disorder characterized by severe limb, craniofacial, and organ abnormalities and often intellectual disabilities. The genetic basis of RBS is rooted in loss-of-function mutations in the essential N-acetyltransferase ESCO2 which is conserved from yeast (Eco1/Ctf7) to humans. ESCO2/Eco1 regulate many cellular processes that impact chromatin structure, chromosome transmission, gene expression, and repair of the genome. The etiology of RBS remains contentious with current models that include transcriptional dysregulation or mitotic failure. Here, we report evidence that supports an emerging model rooted in defective DNA damage responses. First, the results reveal that redox stress is elevated in both eco1 and cohesion factor Saccharomyces cerevisiae mutant cells. Second, we provide evidence that Eco1 and cohesion factors are required for the repair of oxidative DNA damage such that ECO1 and cohesin gene mutations result in reduced cell viability and hyperactivation of DNA damage checkpoints that occur in response to oxidative stress. Moreover, we show that mutation of ECO1 is solely sufficient to induce endogenous redox stress and sensitizes mutant cells to exogenous genotoxic challenges. Remarkably, antioxidant treatment desensitizes eco1 mutant cells to a range of DNA damaging agents, raising the possibility that modulating the cellular redox state may represent an important avenue of treatment for RBS and tumors that bear ESCO2 mutations.
Topics: Acetyltransferases; Cell Cycle Proteins; Chromatids; Chromosomal Proteins, Non-Histone; Craniofacial Abnormalities; Ectromelia; Humans; Hypertelorism; Nuclear Proteins; Oxidation-Reduction; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 34897432
DOI: 10.1093/g3journal/jkab426 -
Nature Jul 2009Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely...
Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a marked increase in incidence in the early 1960s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative. This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation. Both X-irradiation and thalidomide-induced phocomelia have been interpreted as patterning defects in the context of the progress zone model, which states that a cell's proximodistal identity is determined by the length of time spent in a distal limb region termed the 'progress zone'. Indeed, studies of X-irradiation-induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the progress zone model. Here, using a combination of molecular analysis and lineage tracing in chick, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. Because skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the aetiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that proximodistal patterning is unaffected after X-irradiation does not support the predictions of the progress zone model.
Topics: Animals; Body Patterning; Bone and Bones; Cell Death; Cell Differentiation; Cell Lineage; Cell Proliferation; Chick Embryo; Chondrogenesis; Ectromelia; Gene Expression Regulation, Developmental; Limb Buds; Reproducibility of Results; Stem Cells; Thalidomide; Time Factors; X-Rays
PubMed: 19553938
DOI: 10.1038/nature08117