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Medicina Oral, Patologia Oral Y Cirugia... Nov 2017Apert Syndrome (AS), or type I acrocephalosyndactyly, is a rare, congenital craniosynostosis condition resulting from missense mutations in the gene encoding fibroblast... (Review)
Review
BACKGROUND
Apert Syndrome (AS), or type I acrocephalosyndactyly, is a rare, congenital craniosynostosis condition resulting from missense mutations in the gene encoding fibroblast growth factor receptor 2. It is characterized by three specific clinical features: brachycephalic skull; midface hypoplasia, and limb abnormalities (syndactyly of hands and feet). The disorder exhibits variable presentations in bones, brain, skin, internal organs, and in the oral/maxillofacial region. The aim of the present paper was to show the main results from a systematic review of AS.
MATERIAL AND METHODS
A search of the literature was performed from April to June 2016 in five electronic databases. Clinical interventional or observational studies, reviews, and case reports were included. The present systematic review was carried out strictly following PRISMA and Cochrane Collaboration criteria.
RESULTS
A total of 129 potential references were identified. After reviewing titles and abstracts, 77 of these did not meet the desired criteria and were discarded. The full text of the remaining 52 manuscripts was critically screened. Finally, 35 relevant papers were identified for inclusion in the present systematic review and classified according to topic type.
CONCLUSIONS
According to the information gathered, dentistry practitioners must be able to supply an early diagnosis through the recognition of AS clinical features and provide correct oral management. Additionally, they should be integrated in a multidisciplinary medical care team in order to improve the quality of life of the affected patients.
Topics: Acrocephalosyndactylia; Child; Dental Care; Humans
PubMed: 29053644
DOI: 10.4317/medoral.21628 -
Ultrasound in Obstetrics & Gynecology :... Apr 2017The majority of studies on fetal ventriculomegaly have focused on the perinatal and long-term outcomes in fetuses with an antenatal diagnosis of bilateral... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The majority of studies on fetal ventriculomegaly have focused on the perinatal and long-term outcomes in fetuses with an antenatal diagnosis of bilateral ventriculomegaly. The aim of this study was to undertake a systematic review and meta-analysis to quantify the perinatal and long-term outcomes in fetuses diagnosed in the second or third trimester of pregnancy with isolated unilateral ventriculomegaly.
METHODS
MEDLINE, EMBASE and The Cochrane Library were searched electronically. Outcomes investigated included incidence of aneuploidy, congenital infection, progression of ventriculomegaly, associated brain and extracerebral abnormalities in the apparently isolated cases and neurodevelopmental delay in both apparently and truly isolated cases. Sensitivity analysis was performed according to whether the ventriculomegaly was mild/moderate (atrial width < 15 mm) or severe (atrial width ≥ 15 mm). Reference lists within relevant articles and reviews were hand-searched for additional reports. Cohort and case-control studies were included. Meta-analysis of proportions was used, and between-study heterogeneity was assessed using the I test.
RESULTS
The search yielded 2053 citations. The full text was retrieved for 202, and 11 studies were included in the systematic review. In fetuses with apparently isolated unilateral ventriculomegaly, no chromosomal abnormalities were identified and the pooled prevalence of congenital infection was 8.2% (95% CI, 3.6-14.5%). The pooled prevalence of additional brain abnormalities detected prenatally and postnatally by magnetic resonance imaging was 5.1% (95% CI, 0.2-16.1%) and 6.4% (95% CI, 0.3-19.4%), respectively. The pooled prevalence of abnormal neurodevelopment was 5.9% (95% CI, 2.2-11.2%) in apparently isolated cases with an atrial width of < 15 mm, and it was 7.0% (95% CI, 3.2-12.2%) in fetuses with truly isolated unilateral ventriculomegaly. Most cases with apparently isolated ventriculomegaly were classified as mild/moderate (93.5%) and therefore the outcomes in this group were similar to those in the whole cohort of apparently isolated ventriculomegaly.
CONCLUSIONS
The prevalence of aneuploidy, congenital infection and neurodevelopmental delay in fetuses with a prenatal diagnosis of isolated unilateral ventriculomegaly is likely to be low. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Aneuploidy; Congenital Abnormalities; Female; Fetal Diseases; Humans; Hydrocephalus; Infections; Neurodevelopmental Disorders; Perinatal Care; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Ultrasonography, Prenatal
PubMed: 27091707
DOI: 10.1002/uog.15943 -
Cureus Sep 2023A specific type of neurodegeneration with brain iron accumulation (NBIA) falls under the omit phenotypic continuum-early childhood development of progressive... (Review)
Review
A specific type of neurodegeneration with brain iron accumulation (NBIA) falls under the omit phenotypic continuum-early childhood development of progressive pantothenate kinase-associated neurodegeneration (PKAN). Classic PKAN is distinguished from atypical PKAN by stiffness, dystonia, dysarthria, and choreoathetosis. Pigmentary retinal degeneration is a widespread cause of classic PKAN. Atypical PKAN is distinguished by a later onset (>10 years), noticeable speech abnormalities, psychological disorders, and slower disease development. Studies designed to support various PKAN therapeutic strategies have highlighted the intricacy of coenzyme A (CoA) metabolism and the limitations of our present understanding of disease causation. Therefore, improvements in our knowledge of the causes and therapy of PKAN may have ramifications for our comprehension of other, more prevalent diseases. They may also shed fresh light on the physiological significance of CoA, a cofactor essential for the operation of several cellular metabolic processes. The existence of low but considerable PANK2 expression, which can be elevated in some mutations, provides necessary information that can justify using a hefty dose of pantothenate as a treatment. A more effective therapeutic approach can be achieved by comparing the effects of various currently available pharmacological alternatives on the pathophysiological alterations in fibroblasts and neuronal cells obtained from PKAN patients. The objective of this study is to educate and inform people about PKAN disease conditions such as treatment, diagnosis, and complications. These cell models will also help evaluate the effectiveness of future medicinal innovations. This review discusses the neurodegeneration generated by pantothenate kinase in cellular models, iron/lipofuscin in pantothenate kinase-related neurodegeneration, and treatment and diagnosis of PKAN.
PubMed: 37900501
DOI: 10.7759/cureus.46135 -
Neurology Jul 2014To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for predicting symptom onset in ADAD.
METHODS
We have collected individual-level data on ages at symptom onset and death from 387 ADAD pedigrees, compiled from 137 peer-reviewed publications, the Dominantly Inherited Alzheimer Network (DIAN) database, and 2 large kindreds of Colombian (PSEN1 E280A) and Volga German (PSEN2 N141I) ancestry. Our combined dataset includes 3,275 individuals, of whom 1,307 were affected by ADAD with known age at symptom onset. We assessed the relative contributions of several factors in influencing age at onset, including parental age at onset, age at onset by mutation type and family, and APOE genotype and sex. We additionally performed survival analysis using data on symptom onset collected from 183 ADAD mutation carriers followed longitudinally in the DIAN Study.
RESULTS
We report summary statistics on age at onset and disease course for 174 ADAD mutations, and discover strong and highly significant (p < 10(-16), r2 > 0.38) correlations between individual age at symptom onset and predicted values based on parental age at onset and mean ages at onset by mutation type and family, which persist after controlling for APOE genotype and sex.
CONCLUSIONS
Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research.
Topics: Age of Onset; Alzheimer Disease; Chromosome Disorders; Genes, Dominant; Humans
PubMed: 24928124
DOI: 10.1212/WNL.0000000000000596 -
Seizure Apr 2021Dravet Syndrome (DS) is a rare and severe infantile-onset epileptic encephalopathy. DS research focuses mainly on children. We did a systematic review, completed on... (Review)
Review
Dravet Syndrome (DS) is a rare and severe infantile-onset epileptic encephalopathy. DS research focuses mainly on children. We did a systematic review, completed on January 18, 2021, examining the number of clinical DS studies. We show that there are 208 studies on children exclusively, 28 studies on adults exclusively, and 116 studies involving adults and children combined. This 7:1 ratio of children to adult studies exclusively shows the dearth of research that addresses long-term natural history of DS into adulthood. Through this systematic review, we examine the most up-to-date information in DS adults as it pertains to seizures, electroencephalogram, imaging, treatment, motor abnormalities, cognitive and social behavior outcomes, cardiac abnormalities, sleep disturbances, diagnosis in adults, and mortality. Overall, the frequency of seizures increases in the first decade of life and then myoclonic, atypical absences and focal seizures with impaired awareness tend to decrease in frequency or even disappear in adulthood. Adults tend to have a notable reduction in status epilepticus, especially after 30 years of age. Parkinsonian features were seen in patients as young as 19 years old and are more severe in older patients, suggesting a progression of the parkinsonian symptoms. In adulthood, patients continue to present with behavior problems, associated with a lower health-related quality of life. The leading reported cause of death in DS adults is Sudden Unexpected Death in Epilepsy (SUDEP). Further studies in older adults are needed to understand the long-term outcomes of patients with DS.
Topics: Adult; Epilepsies, Myoclonic; Humans; Infant; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Quality of Life; Spasms, Infantile; Young Adult
PubMed: 33677403
DOI: 10.1016/j.seizure.2021.02.025 -
The Cochrane Database of Systematic... Feb 2023Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains... (Review)
Review
BACKGROUND
Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow, leading to haemolytic anaemia. The life-long management of the general health effects of thalassaemia is highly challenging, and failure to deal with dental and orthodontic complications exacerbates the public health, financial and personal burden of the condition. There is a lack of evidence-based guidelines to help care seekers and providers manage such dental and orthodontic complications. This review aimed to evaluate the available evidence on methods for treating dental and orthodontic complications in people with thalassaemia to inform future recommendations. This is an update of a Cochrane Review first published in 2019.
OBJECTIVES
To assess different methods for treating dental and orthodontic complications in people with thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register in September 2022, and we searched nine online databases and trials registries in January 2022. We searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organisations, pharmaceutical companies and researchers working in this field.
SELECTION CRITERIA
We searched for published or unpublished randomised controlled trials (RCTs) that evaluated treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, sex and ethnic origin.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the 37,242 titles retrieved by the search. After deduplication, we identified two potentially relevant RCTs. On assessing their eligibility against our inclusion and exclusion criteria, we excluded one and included the other.
MAIN RESULTS
We included one parallel-design RCT conducted in Saudi Arabia and involving 29 participants (19 males, 10 females) with thalassaemia. It aimed to assess the effectiveness of photodynamic therapy as an adjuvant to conventional full-mouth ultrasonic scaling for the treatment of gingivitis. The average age of participants was around 23 years. There is very low-certainty evidence from this trial that full-mouth ultrasonic scaling plus photodynamic therapy compared to full-mouth ultrasonic scaling alone may improve gingival index score and bleeding on probing after 12 weeks in people with thalassaemia. We found no studies that assessed other interventions for the various dental or orthodontic complications of thalassaemia.
AUTHORS' CONCLUSIONS
Although the included study showed greater reduction in gingivitis in the group treated with full-mouth ultrasonic scaling plus photodynamic therapy, the evidence is of very low certainty. The study had unclear risk of bias, a short follow-up period and no data on safety or adverse effects. We cannot make definitive recommendations for clinical practice based on the limited evidence of a single trial. Future studies will very likely affect the conclusions of this review. This review highlights the need for high-quality RCTs that investigate the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia. It is crucial that future trials assess adverse effects of interventions.
Topics: Male; Female; Humans; Thalassemia; Gingivitis
PubMed: 36732291
DOI: 10.1002/14651858.CD012969.pub3 -
The World Journal of Men's Health Jan 2023Globozoospermia is a genetic syndrome characterized by the presence of round-headed spermatozoa and infertility due to the inability of these spermatozoa to fertilize...
PURPOSE
Globozoospermia is a genetic syndrome characterized by the presence of round-headed spermatozoa and infertility due to the inability of these spermatozoa to fertilize the oocyte. In this article, we present the clinical case of a young globozoospermic patient with a new, not yet described mutation of the gene. We also performed a systematic review of the literature on gene mutations, the outcome of assisted reproductive techniques, and the risk of transmission of abnormalities to the offspring in patients with globozoospermia and made recommendations to offer a more appropriate clinical management of these patients.
MATERIALS AND METHODS
We performed a systematic search in the PubMed, Google Scholar, and Scopus databases from their inception to December 2021. The search strategy included the combination of the following Medical Subjects Headings (MeSH) terms and keywords: "globozoospermia", "round-headed spermatozoa", "round head spermatozoa", "intracytoplasmic sperm injection", "ICSI", "offspring", "child health", "assisted reproductive technique outcome". All the eligible studies were selected following the PECOS (Population, Exposure, Comparison/Comparator, Outcomes, Study design) model. The quality of included studies was assessed by applying the "Cambridge Quality Checklists".
RESULTS
The main genes involved in the pathogenesis of globozoospermia are , , , , , , , and genes. Other genes could also play a role. These include , , , , , , and . Globozoospermic patients should undergo ART to achieve fertility. In particular, intracytoplasmic sperm injection with assisted oocyte activation or intracytoplasmic morphologically-selected sperm injection appears to be associated with a higher success rate. Patients with globozoospermia should also be evaluated for the high rate of sperm aneuploidy which appears to influence the success rate of ART but does not appear to be associated with an increased risk of transmission of genetic abnormalities to offspring.
CONCLUSIONS
This systematic review summarizes the evidence on the gene panel to be evaluated, ICSI outcomes, and the health of the offspring in patients with globozoospermia. Evidence-based recommendations on the management of patients with globozoospermia are provided.
PubMed: 36047070
DOI: 10.5534/wjmh.220020 -
Journal of Ophthalmology 2022Alport syndrome (AS) is a severe, rare hereditary disorder that can lead to end-stage renal disease, auditory degeneration, and ocular abnormalities. Despite extensive... (Review)
Review
OBJECTIVES
Alport syndrome (AS) is a severe, rare hereditary disorder that can lead to end-stage renal disease, auditory degeneration, and ocular abnormalities. Despite extensive research on AS in relation to auditory and renal disorders, more research is needed on the ocular presentations of AS. This systematic review aims to summarize the common ocular abnormalities in patients with AS and to explore the potential treatment options for these irregularities.
METHODS
The PubMed, MEDLINE, and EMBASE databases were systematically searched from January 1977 to April 2022. Only papers that were published in the English language and explored the ocular abnormalities in AS patients were selected. We manually searched reference lists of included papers for additional studies.
RESULTS
A total of 23 articles involving 195 patients were included in this review. The common ocular manifestations in AS patients are lenticonus, macular holes, fleck retinopathy, and thinning of the macula. Although published literature has described the use of cataract surgeries and vitrectomies as standard surgical techniques to alleviate ocular abnormalities in non-AS patients, it must be noted that surgical techniques have not been evaluated in a large research study as a solution for AS abnormalities. Another prospective treatment for AS is gene therapy through the reversion of causative variants to wild type or exon-skipping therapy for -linked AS with truncating mutations. Gene therapy, however, remains unable to treat alterations that occur in the fetal and early development phase of the disease.
CONCLUSIONS
The review found no definitive conclusions regarding the efficacy and safety of surgical techniques and gene therapy in AS patients. Recognition of ocular abnormalities through an ophthalmic examination with an optical coherence tomography (OCT) and slit-lamp examination is critical to the medical field, as ophthalmologists can aid nephrologists and other physicians in diagnosing AS. Early diagnosis and care can minimize the risk of detrimental ocular outcomes, such as blindness and retinal detachment.
PubMed: 36119140
DOI: 10.1155/2022/9250367 -
Acta Obstetricia Et Gynecologica... Jan 2017The aim of this study was to review the performance of non-invasive prenatal testing (NIPT) for detection of trisomy 21, 18 and 13 (T21, T18 and T13) in a general... (Meta-Analysis)
Meta-Analysis Review
Analysis of cell-free fetal DNA in maternal blood for detection of trisomy 21, 18 and 13 in a general pregnant population and in a high risk population - a systematic review and meta-analysis.
INTRODUCTION
The aim of this study was to review the performance of non-invasive prenatal testing (NIPT) for detection of trisomy 21, 18 and 13 (T21, T18 and T13) in a general pregnant population as well as to update the data on high-risk pregnancies.
MATERIAL AND METHODS
Systematic review and meta-analysis. PubMed, Embase and the Cochrane Library were searched. Methodological quality was rated using QUADAS and scientific evidence using GRADE. Summary measures of diagnostic accuracy were calculated using a bivariate random-effects model.
RESULTS
In a general pregnant population, there is moderate evidence that the pooled sensitivity is 0.993 (95% CI 0.955-0.999) and specificity was 0.999 (95% CI 0.998-0.999) for the analysis of T21. Pooled sensitivity and specificity for T13 and T18 was not calculated in this population due to the low number of studies. In a high-risk pregnant population, there is moderate evidence that the pooled sensitivities for T21 and T18 are 0.998 (95% CI 0.981-0.999) and 0.977 (95% CI 0.958-0.987) respectively, and low evidence that the pooled sensitivity for T13 is 0.975 (95% CI 0.819-0.997). The pooled specificity for all three trisomies is 0.999 (95% CI 0.998-0.999).
CONCLUSIONS
This is the first meta-analysis using GRADE that shows that NIPT performs well as a screen for trisomy 21 in a general pregnant population. Although the false positive rate is low compared with first trimester combined screening, women should still be advised to confirm a positive result by invasive testing if termination of pregnancy is under consideration.
Topics: Cell-Free System; Chromosome Disorders; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 18; DNA; Down Syndrome; Female; Genetic Testing; Humans; Pregnancy; Pregnancy, High-Risk; Prenatal Diagnosis; Sensitivity and Specificity; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 27779757
DOI: 10.1111/aogs.13047 -
Journal of Thoracic Oncology : Official... Aug 2011Greater understanding of molecular pathways important in cell growth and proliferation of thoracic malignancies, particularly non-small cell lung cancer (NSCLC), has... (Review)
Review
INTRODUCTION
Greater understanding of molecular pathways important in cell growth and proliferation of thoracic malignancies, particularly non-small cell lung cancer (NSCLC), has resulted in intense clinical and translational research. There is now considerable interest in personalizing treatment based on an understanding of tumor histology and molecular abnormalities. However, there is a multiplicity of data, often with discordant results resulting in confusion and uncertainty among clinicians.
METHODS
We conducted a systematic review and a consensus meeting of Canadian lung cancer oncologists and pathologists to make recommendations on the use of biomarkers in NSCLC. PubMed covering 2005 to March 2010 was searched using MESH terms for NSCLC and randomized trials, plus text words for the biomarkers of interest. Conference proceedings from 2005 to 2009 ASCO, ESMO, IASLC, and USCAP were also searched. The articles were reviewed by pairs of oncologists and pathologists to determine eligibility for inclusion.
RESULTS
Ten oncologists and pathologists reviewed and summarized the literature at a meeting attended by 37 individuals. Draft recommendations were formulated and agreed upon by consensus process. There is some evidence that histology is prognostic for survival. There is evidence from multiple randomized clinical trials to recommend the following: histologic subtype is predictive of treatment efficacy and for some agents toxicity. Immunohistochemistry testing should be performed on NSCLC specimens that cannot be classified accurately with conventional H&E staining. As EGFR mutations are predictive of benefit from tyrosine kinase inhibitors, diagnostic NSCLC samples should be routinely tested for EGFR-activating mutations. Clinical data on K-RAS mutations are inconsistent, therefore testing is not recommended. There is insufficient evidence to recommend other biomarker testing. No biomarkers to date reliably predict improved efficacy for anti-VEGF therapy. Routine assessment for EML4/ALK mutations is not recommended at present, although emerging data suggest that it may become valuable in the near future.
CONCLUSIONS
Assessment of NSCLC biomarkers is becoming increasingly important. Therefore, adequate diagnostic material must be obtained for accurate histologic subtyping and relevant molecular biology assays.
Topics: Biomarkers, Tumor; Canada; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Consensus; Humans; Lung Neoplasms; Practice Guidelines as Topic
PubMed: 21709590
DOI: 10.1097/JTO.0b013e318220cb8e