A Peruvian Child with 18p-/18q+ Syndrome and Persistent Microscopic Hematuria.
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ABSTRACT:
SUBMITTER: Poterico JA
PROVIDER: S-EPMC5683951 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceAsymptomatic microscopic hematuria (AMH) is highly prevalent and may signal occult genitourinary (GU) malignant abnormality. Common diagnostic approaches differ in their costs and effectiveness in detecting cancer. Given the low prevalence of GU malignant abnormality among patients with AMH, it is important to quantify the cost implications of detecting cancer for each approach.ObjectiveTo estimate the effectiveness, costs, and incremental cost per cancer detected (ICCD) for 4 common diagnostic approaches evaluating AMH.Design, setting, and participantsA decision-analytic model-based cost-effectiveness analysis using inputs from the medical literature. PubMed searches were performed to identify relevant literature for all key model inputs, each of which was derived from the clinical study with the most robust data and greatest applicability. Analysis included adult patients with AMH on routine urinalysis with subgroups of high-risk patients (males, smokers, age ≥50 years) seen in the primary care or urologic referral setting.InterventionsFour diagnostic approaches were evaluated relative to the reference case of no evaluation: (1) computed tomography (CT) alone; (2) cystoscopy alone; (3) CT and cystoscopy combined; and (4) renal ultrasound and cystoscopy combined.Main outcomes and measuresAt termination of the diagnostic period, cancers detected, costs (payer perspective), and ICCD per 10 000 patients evaluated for AMH.ResultsOf the 4 diagnostic approaches analyzed, CT alone was dominated by all other strategies, detecting 221 cancers at a cost of $9 300 000. Ultrasound and cystoscopy detected 245 cancers and was most cost-effective with an ICCD of $53 810. Replacing ultrasound with CT detected just 1 additional cancer at an ICCD of $6 480 484. Ultrasound and cystoscopy remained the most cost-effective approach in subgroup analysis. The model was not sensitive to any inputs within the proposed ranges. Using probabilistic sensitivity analysis, ultrasound and cystoscopy was the dominant strategy in 100% of simulations.Conclusions and relevanceThe combination of renal ultrasound and cystoscopy is the most cost-effective among 4 diagnostic approaches for the initial evaluation of AMH. The use of ultrasound in lieu of CT as the first-line diagnostic strategy will optimize cancer detection and reduce costs associated with evaluation of AMH. Given our findings, we need to critically evaluate the appropriateness of our current clinical practices, and potentially alter our guidelines to reflect the most effective screening strategies for patients with AMH.
| S-EPMC5818826 | biostudies-literature
Project description:PURPOSE:Computerized tomography urogram is recommended when investigating patients with hematuria. We determined the incidence of urinary tract cancer and compared the diagnostic accuracy of computerized tomography urogram to that of renal and bladder ultrasound for identifying urinary tract cancer. MATERIALS AND METHODS:The DETECT (Detecting Bladder Cancer Using the UroMark Test) I study is a prospective observational study recruiting patients 18 years old or older following presentation with macroscopic or microscopic hematuria at a total of 40 hospitals. All patients underwent cystoscopy and upper tract imaging comprising computerized tomography urogram and/or renal and bladder ultrasound. RESULTS:A total of 3,556 patients with a median age of 68 years were recruited in this study, of whom 2,166 underwent renal and bladder ultrasound, and 1,692 underwent computerized tomography urogram in addition to cystoscopy. The incidence of bladder, renal and upper tract urothelial cancer was 11.0%, 1.4% and 0.8%, respectively, in macroscopic hematuria cases. Patients with microscopic hematuria had a 2.7%, 0.4% and 0% incidence of bladder, renal and upper tract urothelial cancer, respectively. The sensitivity and negative predictive value of renal and bladder ultrasound to detect renal cancer were 85.7% and 99.9% but they were 14.3% and 99.7%, respectively, to detect upper tract urothelial cancer. Renal and bladder ultrasound was poor at identifying renal calculi. Renal and bladder ultrasound sensitivity was lower than that of computerized tomography urogram to detect bladder cancer (each less than 85%). Cystoscopy had 98.3% specificity and 83.9% positive predictive value. CONCLUSIONS:Computerized tomography urogram can be safely replaced by renal and bladder ultrasound in patients who have microscopic hematuria. The incidence of upper tract urothelial cancer is 0.8% in patients with macroscopic hematuria and computerized tomography urogram is recommended. Patients with suspected renal calculi require noncontrast renal tract computerized tomography. Imaging cannot replace cystoscopy to diagnose bladder cancer.
| S-EPMC6179963 | biostudies-literature
Project description:Deletion on the short arm of chromosome 18 is a rare disorder characterized by intellectual disability, growth retardation, and craniofacial malformations (such as prominent ears, microcephaly, ptosis, and a round face). The phenotypic spectrum is wide, encompassing a range of abnormalities from minor congenital malformations to holoprosencephaly. We present a case of a 2-year-old girl with ptosis, a round face, broad neck with low posterior hairline, short stature, and panhypopituitarism. She underwent ventilation tube insertion for recurrent otitis media with effusion. Brain magnetic resonance imaging showed an ectopic posterior pituitary gland and a shallow, small sella turcica with poor visualization of the pituitary stalk. Cytogenetic and chromosomal microarray analysis revealed a de novo deletion on the short arm of chromosome 18 (arr 18p11.32p11.21[136,227-15,099,116]x1). She has been treated with recombinant human growth hormone (GH) therapy since the age of 6 months after diagnosis of GH deficiency. Her growth rate has improved without any side effects from the GH treatment. This case expands the phenotypic spectrum of 18p deletion syndrome and emphasizes the positive impact of GH therapy on linear growth in this syndrome characterized by growth deficiency. Further studies are required to define the genotype-phenotype correlation according to size and loci of the deletion in 18p deletion syndrome and to predict prognosis.
| S-EPMC6449612 | biostudies-literature
Project description:The latest decades are characterized by an enormous progression in the field of human genetics. In consequences, for various phenotypic manifestations, genetic testing could identify a specific underlying cause. An estimated incidence for all types of 18q deletions is one in 55 000 births predominant on females. About 94% of cases with 18q deletion syndrome appearance are de novo, and the remaining 6% are the inherited from a parent carrying a balanced chromosomal translocation. We present the case of a 35-year-old female who was admitted in our Unit for a second ultrasound opinion after being diagnosed at the second trimester scan at gestational age of 21 weeks of pregnancy with multiple brain and heart malformations, having the recommendation for fetal magnetic resonance imaging (MRI). Further investigations included genetic analysis and pathological examination. Major malformations diagnosed and confirmed were agenesis of the corpus callosum, ventriculomegaly with dilated fourth ventricle, partial agenesis of vermis, bilateral anophthalmia with wide nasal base and left cleft lip. Additional, cardiac malformation, with an important ventricular septal defect and overriding aorta were noted. The results of the microarray analysis showed an abnormal fetal karyotype with a loss of 30.5 basis identified in the long arm of chromosome 18. Although most of the cases of 18q deletion are sporadically or de novo, could be cases where the possible existing syndromes can be inherited from a healthy or mild affected parent. Therefore, in order to establish the recurrence risk, parental karyotypes are recommended.
| S-EPMC8112787 | biostudies-literature
Project description:RationaleThe chromosome 18p deletion syndrome is a syndrome with a deletion of all or a portion of the short arm of the chromosome 18. The phenotypes of the chromosome 18p deletion syndrome vary widely among individuals due to differences in size and breakpoints and the involved genes on the deletions. Given the varied and untypical clinical presentation of this syndrome, the prenatal diagnosis of the syndrome still presents as a challenge.Patient concernsWe described 4 China cases with different chromosomal breakpoints. In case 1, a woman who with mild phenotypes gave birth to a severely deformed fetus. Three other cases were for prenatal diagnosis. Their phenotypes are the increased nuchal translucency (INT) and the noninvasive prenatal testing (NIPT) indicated deletions on the chromosome 18p and severe hydronephrosis respectively.DiagnosisThe 4 cases were diagnosed with chromosome 18p deletion syndrome through karyotype analysis and array-based comparative genomic hybridization (array-CGH).InterventionsKaryotype analysis and array-based comparative genomic hybridization were used to analyze the abnormal chromosome.OutcomesCase 1 and case 2 revealed 11.51 and 12.39 Mb deletions in 18p11.32p11.21. Case 3 revealed 7.1 Mb deletions in 18p11.3218p11.23. Case 4 revealed 9.9 Mb deletions in 18p11.3218p11.22.LessonsIn our report, we are the first to report that mother and progeny who have the same chromosomal breakpoint have different phenotypes, significantly. In addition, we found a new phenotype of chromosome 18p deletion syndrome in fetus, which can enrich the phenotypes of this syndrome in the prenatal diagnosis. Finally, we demonstrate that the individuals with different chromosomal breakpoints of 18p deletion syndrome have different phenotypes. On the other hand, the individuals with the same chromosomal breakpoints of 18p deletion syndrome may also have remarkably different phenotypes.
| S-EPMC8104293 | biostudies-literature
Project description:IntroductionThe vast majority of patients who undergo a diagnostic evaluation for microscopic hematuria (MH) do not have occult bladder cancer. Identifying patients with MH at high risk of harboring bladder cancer can allow for a risk adjusted approach to diagnostic interventions with the goal of safely reducing unnecessary evaluations.MethodsPatients with a new diagnosis of microhematuria during an 8.5 year period were retrospectively identified. All patients who had a complete MH evaluation were randomized to a training or a validation cohort. Logistic regression analysis was performed in the training cohort to identify factors related to a bladder cancer diagnosis and to develop our model. Receiver operating curves to identify bladder cancer were constructed for the training and validation cohort and tested for their ability to discriminate true cases. A nomogram to predict a bladder cancer diagnosis was created.ResultsIn 4,178 patients split into training and validation cohorts, those diagnosed with bladder cancer were shown to be older, have a greater degree of MH (more RBC/hpf), and were former or current smokers. A nomogram created using this model was able to predict risk of a bladder cancer diagnosis with good discrimination (areas under the curve 0.79, 95% CI 0.75-0.83). A cutoff of 0.01 probability demonstrated a sensitivity of 99.1% and a negative predictive value of 99.7%.ConclusionA nomogram can accurately predict the risk of bladder cancer diagnosed during the evaluation of MH and can potentially be used avoid a significant number of work ups in those at the lowest risk.
| S-EPMC7150636 | biostudies-literature
Project description:BackgroundChromosome abnormalities that segregate with a disease phenotype can facilitate the identification of disease loci and genes. The relationship between chromosome 18 anomalies with severe intellectual disability has attracted the attention of cytogeneticists worldwide. Duplications of the X chromosome can cause intellectual disability in females with variable phenotypic effects, due in part to variations in X-inactivation patterns. Additionally, deletions of the 7qter region are associated with a range of phenotypes.ResultsWe report the first case of de novo microdeletion at 7q and 18p, 18q partial trisomy, microduplication at Xp associated to intellectual disability in a Brazilian child, presenting a normal karyotype. Karyotyping showed any chromosome alteration. Chromosomal microarray analysis detected a de novo microdeletion at 18p11.32 and 18q partial trisomy, an inherited microdeletion at 7q31.1 and a de novo microduplication at Xp22.33p21.3.ConclusionsOur report illustrates a case that presents complex genomic imbalances which may contribute to a severe clinical phenotypes. The rare and complex phenotypes have to be investigated to define the subsets and allow the phenotypes classification.
| S-EPMC4099144 | biostudies-literature
Project description:BackgroundChromosome 18p deletion syndrome is a disease caused by the complete or partial deletion of the short arm of chromosome 18, there were few cases reported about the prenatal diagnosis of 18p deletion syndrome. Noninvasive prenatal testing (NIPT) is widely used in the screening of common fetal chromosome aneuploidy. However, the segmental deletions and duplications should also be concerned. Except that some cases had increased nuchal translucency or holoprosencephaly, most of the fetal phenotype of 18p deletion syndrome may not be evident during the pregnancy, 18p deletion syndrome was always accidentally discovered during the prenatal examination.Case presentationsIn our case, we found a pure partial monosomy 18p deletion during the confirmation of the result of NIPT by copy number variation sequencing (CNV-Seq). The result of NIPT suggested that there was a partial or complete deletion of X chromosome. The amniotic fluid karyotype was normal, but result of CNV-Seq indicated a 7.56 Mb deletion on the short arm of chromosome 18 but not in the couple, which means the deletion was de novo deletion. Finally, the parents chose to terminate the pregnancy.ConclusionsTo our knowledge, this is the first case of prenatal diagnosis of 18p deletion syndrome following NIPT.NIPT combined with ultrasound may be a relatively efficient method to screen chromosome microdeletions especially for the 18p deletion syndrome.
| S-EPMC6925888 | biostudies-literature
Project description:Facioscapulohumeral muscular dystrophy (FSHD) is most often associated with variegated expression in somatic cells of the normally repressed DUX4 gene within the D4Z4-repeat array. The most common form, FSHD1, is caused by a D4Z4-repeat array contraction to a size of 1-10 units (normal range 10-100 units). The less common form, FSHD2, is characterized by D4Z4 CpG hypomethylation and is most often caused by loss-of-function mutations in the structural maintenance of chromosomes hinge domain 1 (SMCHD1) gene on chromosome 18p. The chromatin modifier SMCHD1 is necessary to maintain a repressed D4Z4 chromatin state. Here, we describe two FSHD2 families with a 1.2-Mb deletion encompassing the SMCHD1 gene. Numerical aberrations of chromosome 18 are relatively common and the majority of 18p deletion syndrome (18p-) cases have, such as these FSHD2 families, only one copy of SMCHD1. Our finding therefore raises the possibility that 18p- cases are at risk of developing FSHD. To address this possibility, we combined genome-wide array analysis data with D4Z4 CpG methylation and repeat array sizes in individuals with 18p- and conclude that approximately 1:8 18p- cases might be at risk of developing FSHD.
| S-EPMC4475473 | biostudies-literature
Project description:The loin pain hematuria syndrome (LPHS) creates a considerable burden, both for patients afflicted with the disease and for those involved in medical management and diagnosis. To date, the diagnosis of LPHS remains one of exclusion, with some speculation regarding the extent of actual pathology. We report ureteroscopic findings in 2 cases of LPHS. These findings provide objective confirmation of underlying pathology in a difficult-to-manage disease process.
| S-EPMC2643052 | biostudies-literature