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Frontiers in Endocrinology 2023Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital...
BACKGROUND
Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital heart disease, renal anomalies, lymphatic malformations, chest deformities, cryptorchidism in males.
METHODS
In this narrative review, we summarized the available data on puberty and gonadal function in NS subjects and the role of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway in fertility. In addition, we have reported our personal experience on pubertal development and vertical transmission in NS.
CONCLUSIONS
According to the literature and to our experience, NS patients seem to have a delay in puberty onset compared to the physiological timing reported in healthy children. Males with NS seem to be at risk of gonadal dysfunction secondary not only to cryptorchidism but also to other underlying developmental factors including the MAP/MAPK pathway and genetics. Long-term data on a large cohort of males and females with NS are needed to better understand the impact of delayed puberty on adult height, metabolic profile and well-being. The role of genetic counselling and fertility related-issues is crucial.
Topics: Male; Child; Adult; Female; Humans; Noonan Syndrome; Cryptorchidism; Gonads; Puberty; Mitogen-Activated Protein Kinases
PubMed: 37576960
DOI: 10.3389/fendo.2023.1213098 -
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 -
TheScientificWorldJournal 2022Worldwide, surveys have shown that the frequency of chromosomal disorders among births with congenital anomalies varies greatly from country to country. It is well known... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Worldwide, surveys have shown that the frequency of chromosomal disorders among births with congenital anomalies varies greatly from country to country. It is well known that chromosomal disorders are an important cause of premature death or life-long disability; however, the absence of local epidemiological data on their birth prevalence and outcomes impedes policy and service development in many countries and continents. Therefore, the current systematic review and meta-analysis intend to show the pooled proportion of chromosomal disorders among births with congenital anomalies in Africa.
METHODS
From PubMed, Cochrane Library, and Google Scholar, we systematically reviewed and meta-analyzed the studies that examined the incidence, prevalence, and types of chromosomal disorders using PRISMA guidelines. A weighted inverse variance random-effects model was used to estimate the pooled proportion of chromosomal disorders among births with congenital anomalies.
RESULTS
From the total of 3,569 studies identified, 1,442 were from PubMed, 108 were from Cochrane Library, 1,830 were from Google Scholar, and 189 were from other sources. After duplication was removed, a total of 844 articles remained (2725 were removed by duplication). Finally, 144 full-text studies were reviewed and 60 articles with 52,569 births having congenital anomalies met the inclusion criteria and were selected for this meta-analysis. The pooled proportion of chromosomal disorders among births with congenital anomalies was 8.94% (95% CI; 7.02, 10.86; = 98.8%; < 0.001). . In the current systematic review and meta-analysis, the pooled proportion of chromosomal disorders among births with congenital anomalies in Africa was small. Down syndrome (trisomy 21) accounted for more than 80% of chromosomal disorders. The pooled proportion of chromosome disorders was the highest in North African regions and countries compared to other regions of the continent. Healthcare managers should focus on establishing proper cytogenetic diagnostic facilities in collaboration with well-trained genetic counseling services in the continent.
Topics: Pregnancy; Female; Humans; Chromosome Disorders; Parturition; Prevalence; Africa; Incidence
PubMed: 36561944
DOI: 10.1155/2022/6477596 -
Journal of Pregnancy 2014The aim of this review was to identify clinically significant ultrasound predictors of adverse neonatal outcome in fetal gastroschisis. (Review)
Review
OBJECTIVES
The aim of this review was to identify clinically significant ultrasound predictors of adverse neonatal outcome in fetal gastroschisis.
METHODS
A quasi-systematic review was conducted in PubMed and Ovid using the key terms "gastroschisis," "predictors," "outcome," and "ultrasound."
RESULTS
A total of 18 papers were included. The most common sonographic predictors were intra-abdominal bowel dilatation (IABD), intrauterine growth restriction (IUGR), and bowel dilatation not otherwise specified (NOS). Three ultrasound markers were consistently found to be statistically insignificant with respect to predicting adverse outcome including abdominal circumference, stomach herniation and dilatation, and extra-abdominal bowel dilatation (EABD).
CONCLUSIONS
Gastroschisis is associated with several comorbidities, yet there is much discrepancy in the literature regarding which specific ultrasound markers best predict adverse neonatal outcomes. Future research should include prospective trials with larger sample sizes and use well-defined and consistent definitions of the adverse outcomes investigated with consideration given to IABD.
Topics: Dilatation, Pathologic; Female; Fetal Growth Retardation; Gastroschisis; Humans; Intestines; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Ultrasonography, Prenatal
PubMed: 25587450
DOI: 10.1155/2014/239406 -
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 -
Journal of Ovarian Research Jan 2023Ovarian absence is an uncommon condition that most frequently presents unilaterally. Several etiologies for the condition have been proposed, including torsion, vascular... (Review)
Review
Ovarian absence is an uncommon condition that most frequently presents unilaterally. Several etiologies for the condition have been proposed, including torsion, vascular accident, and embryological defect. A systematic review was conducted to describe the clinical presentation of ovarian absence, as well as its associations with other congenital anomalies, through a systematic search of Cochrane Library, ClinicalTrials.gov, Google Scholar, Ovid Embase, Ovid Medline, PubMed, Scopus, and Web of Science. Exclusion criteria included cases with suspicion for Differences of Sex Development, lack of surgically-confirmed ovarian absence, and karyotypes other than 46XX. Our search yielded 12,120 citations, of which 79 studies were included. 10 additional studies were found by citation chasing resulting in a total 113 cases including two unpublished cases presented in this review. Abdominal/pelvic pain (30%) and infertility/subfertility (19%) were the most frequent presentations. Ovarian abnormalities were not noted in 28% of cases with pre-operative ovarian imaging results. Approximately 17% of cases had concomitant uterine abnormalities, while 22% had renal abnormalities. Renal abnormalities were more likely in patients with uterine abnormalities (p < 0.005). Torsion or vascular etiology was the most frequently suspected etiology of ovarian absence (52%), followed by indeterminate (27%) and embryologic etiology (21%). Most cases of ovarian absence are likely attributable to torsion or vascular accidents, despite many references to the condition as "agenesis" in the literature. Imaging may fail to correctly diagnose ovarian absence, and diagnostic laparoscopy may be preferable in many cases as genitourinary anatomy and fertility considerations can be assessed during the procedure. Fertility is likely minimally or not affected in women with unilateral ovarian absence.
Topics: Humans; Female; Urogenital Abnormalities; Ovary; Uterus
PubMed: 36642704
DOI: 10.1186/s13048-022-01090-1 -
The European Respiratory Journal Oct 2016Few original studies have described the prevalence and severity of clinical symptoms of primary ciliary dyskinesia (PCD). This systematic review and meta-analysis aimed... (Meta-Analysis)
Meta-Analysis Review
Few original studies have described the prevalence and severity of clinical symptoms of primary ciliary dyskinesia (PCD). This systematic review and meta-analysis aimed to identify all published studies on clinical manifestations of PCD patients, and to describe their prevalence and severity stratified by age and sex.We searched PubMed, Embase and Scopus for studies describing clinical symptoms of ≥10 patients with PCD. We performed meta-analyses and meta-regression to explain heterogeneity.We included 52 studies describing a total of 1970 patients (range 10-168 per study). We found a prevalence of 5% for congenital heart disease. For the rest of reported characteristics, we found considerable heterogeneity (I range 68-93.8%) when calculating the weighted mean prevalence. Even after taking into account the explanatory factors, the largest part of the between-studies variance in symptom prevalence remained unexplained for all symptoms. Sensitivity analysis including only studies with test-proven diagnosis showed similar results in prevalence and heterogeneity.Large differences in study design, selection of study populations and definition of symptoms could explain the heterogeneity in symptom prevalence. To better characterise the disease, we need larger, multicentre, multidisciplinary, prospective studies that include all age groups, use uniform diagnostics and report on all symptoms.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Kartagener Syndrome; Male; Middle Aged; Phenotype; Prevalence; Prospective Studies; Regression Analysis; Respiration Disorders; Retrospective Studies; Situs Inversus; Treatment Outcome; Young Adult
PubMed: 27492829
DOI: 10.1183/13993003.00736-2016 -
EuroIntervention : Journal of EuroPCR... Oct 2015Stent placement as treatment for coarctation of the aorta (CoA) has become a more common choice in the last 20 years. Clinical results of CoA stenting are usually... (Meta-Analysis)
Meta-Analysis Review
AIMS
Stent placement as treatment for coarctation of the aorta (CoA) has become a more common choice in the last 20 years. Clinical results of CoA stenting are usually reported in small retrospective case series. This systematic review provides an overview of clinical experience with stenting for CoA.
METHODS AND RESULTS
A systematic review of the reports published between January 1990 and December 2014 after stenting a CoA was performed with a focus on relief of obstruction and lowering of blood pressure. Study and patient characteristics were extracted, as well as pre- and post-stenting aortic diameter in mm, systolic pressure gradient (SPG) and pre- and post-stenting systolic blood pressure (mmHg), periprocedural and follow-up complications. Forty-five articles met the inclusion criteria. Three outcomes were extracted from the articles - aortic diameter, systolic pressure gradient and blood pressure. Diameter increased from 6.4 mm (5.6, 7.3) to 15.1 mm (14.5, 15.7), pressure gradients decreased from 40 mmHg (35, 42) to 4 mmHg (3, 5) and systolic blood pressure decreased from 153 mmHg (148, 158) to 132 mmHg (127, 136). Stent migration was the most common periprocedural complication (2.4%), and mortality was low (0.4%).
CONCLUSIONS
Stenting is an effective treatment with regard to immediate relief of obstruction and direct lowering effect on blood pressure. However, there is a lack of evidence regarding late effectiveness concerning durable blood pressure lowering, and limited information on periprocedural and late complications. This observation calls for a systematic and longer prospective follow-up of patients after CoA stenting.
Topics: Aortic Coarctation; Arterial Pressure; Endovascular Procedures; Foreign-Body Migration; Humans; Risk Factors; Stents; Time Factors; Treatment Outcome
PubMed: 26499220
DOI: 10.4244/EIJV11I6A133 -
Ultrasound in Obstetrics & Gynecology :... Jun 2013Chromosomal microarray analysis (CMA) is utilized in prenatal diagnosis to detect chromosomal abnormalities not visible by conventional karyotyping. A prospective cohort... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Chromosomal microarray analysis (CMA) is utilized in prenatal diagnosis to detect chromosomal abnormalities not visible by conventional karyotyping. A prospective cohort of women undergoing fetal CMA and karyotyping following abnormal prenatal ultrasound findings is presented in the context of a systematic review and meta-analysis of the literature describing detection rates by CMA and karyotyping.
METHODS
We performed a prospective cohort study of 243 women undergoing CMA alongside karyotyping when a structural abnormality was detected on prenatal ultrasound. A systematic review of the literature was also performed. MEDLINE (1970-Dec 2012), EMBASE (1980-Dec 2012) and CINAHL (1982-June 2012) databases were searched electronically. Selected studies included > 10 cases and prenatal CMA in addition to karyotyping. The search yielded 560 citations. Full papers were retrieved for 86, and 25 primary studies were included in the systematic review.
RESULTS
Our cohort study found an excess detection rate of abnormalities by CMA of 4.1% over conventional karyotyping when the clinical indication for testing was an abnormal fetal ultrasound finding; this was lower than the detection rate of 10% (95% CI, 8-13%) by meta-analysis. The rate of detection for variants of unknown significance (VOUS) was 2.1% (95% CI, 1.3-3.3%) when the indication for CMA was an abnormal scan finding. The VOUS detection rate was lower (1.4%; 95% CI, 0.5-3.7%) when any indication for prenatal CMA was meta-analyzed.
CONCLUSION
We present evidence for a higher detection rate by CMA than by karyotyping not just in the case of abnormal ultrasound findings but also in cases of other indications for invasive testing. It is likely that CMA will replace karyotyping in high-risk pregnancies.
Topics: Chromosome Disorders; Female; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Microarray Analysis; Pregnancy; Prenatal Diagnosis; Prospective Studies; Ultrasonography, Prenatal
PubMed: 23512800
DOI: 10.1002/uog.12464 -
Pediatrics Jun 2017Opioid use and abuse have increased dramatically in recent years, particularly among women. (Review)
Review
CONTEXT
Opioid use and abuse have increased dramatically in recent years, particularly among women.
OBJECTIVES
We conducted a systematic review to evaluate the association between prenatal opioid use and congenital malformations.
DATA SOURCES
We searched Medline and Embase for studies published from 1946 to 2016 and reviewed reference lists to identify additional relevant studies.
STUDY SELECTION
We included studies that were full-text journal articles and reported the results of original epidemiologic research on prenatal opioid exposure and congenital malformations. We assessed study eligibility in multiple phases using a standardized, duplicate review process.
DATA EXTRACTION
Data on study characteristics, opioid exposure, timing of exposure during pregnancy, congenital malformations (collectively or as individual subtypes), length of follow-up, and main findings were extracted from eligible studies.
RESULTS
Of the 68 studies that met our inclusion criteria, 46 had an unexposed comparison group; of those, 30 performed statistical tests to measure associations between maternal opioid use during pregnancy and congenital malformations. Seventeen of these (10 of 12 case-control and 7 of 18 cohort studies) documented statistically significant positive associations. Among the case-control studies, associations with oral clefts and ventricular septal defects/atrial septal defects were the most frequently reported specific malformations. Among the cohort studies, clubfoot was the most frequently reported specific malformation.
LIMITATIONS
Variabilities in study design, poor study quality, and weaknesses with outcome and exposure measurement.
CONCLUSIONS
Uncertainty remains regarding the teratogenicity of opioids; a careful assessment of risks and benefits is warranted when considering opioid treatment for women of reproductive age.
Topics: Abnormalities, Drug-Induced; Analgesics, Opioid; Female; Humans; Methadone; Morphine Derivatives; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Research Design
PubMed: 28562278
DOI: 10.1542/peds.2016-4131