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This article discusses a rare case of a specific type of kidney cancer called Wilms tumor with rhabdomyoblastic differentiation. The patient, a 7-year-old boy, had a large renal mass and underwent fine-needle aspiration cytology (FNAC) to diagnose the tumor. The FNAC smears showed a tumor composed of stromal cells with rhabdomyoblastic differentiation. The patient received chemotherapy and surgery, and the tumor was successfully removed. The article also explores different variants of Wilms tumor, including fetal rhabdomyomatous nephroblastoma (FRN) and stromal predominant Wilms tumors. It emphasizes the importance of FNAC and cell-block immunohistochemistry in diagnosing and understanding these rare variants of Wilms tumor. [Extracted from the article]

Historically, specific mutations in WT1 gene have been associated with distinct syndromes based on phenotypic characteristics, including Denys-Drash syndrome (DDS), Frasier syndrome (FS), Meacham syndrome, and WAGR syndrome. DDS is classically defined by the triad of steroid-resistant nephrotic syndrome (SRNS) onset in the first year of life, disorders of sex development (DSD), and a predisposition to Wilms tumor (WT). Currently, a paradigm shift acknowledges a diverse spectrum of presentations beyond traditional syndromic definitions. Consequently, the concept of WT1-related disorders becomes more precise. A genotype–phenotype correlation has been established, emphasizing that the location and type of WT1 mutations significantly influence the clinical presentation, the condition severity, and the chronology of patient manifestations. Individuals presenting with persistent proteinuria, with or without nephrotic syndrome, and varying degrees of kidney dysfunction accompanied by genital malformations should prompt suspicion of WT1 mutations. Recent genetic advances enable a more accurate estimation of malignancy risk in these patients, facilitating a conservative nephron-sparing surgery (NSS) approach in select cases, with a focus on preserving residual kidney function and delaying nephrectomies. Other key management strategies include kidney transplantation and addressing DSD and gonadoblastoma. In summary, recent genetic insights underscore the imperative to implement individualized, integrated, and multidisciplinary management strategies for WT1-related disorders. This approach is pivotal in optimizing patient outcomes and addressing the complexities associated with these diverse clinical manifestations. [ABSTRACT FROM AUTHOR]

Aim: This study reports the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins subsequently diagnosed with Wilms tumour (WAGR syndrome). Methods: Two monozygotic female twins were referred at age 2 months with bilateral corneal opacity. A diagnosis of Peters' anomaly associated to aniridia was made in both eyes of both twins. Physical examination and ultrasonography were carried out at 12 months of age to explore the possibility of WAGR-related anomalies, specifically Wilms tumour. DNA were isolated and subjected to whole exome sequencing. Results: Peters' anomaly associated to aniridia in both eyes as well as bilateral Wilms tumour in both children were diagnosed. Exome analyses showed a large heterozygous deletion encompassing 6 648 473 bp in chromosome 11p13, using Integrative Genomics Viewer and AnnotSV software. Conclusion: WAGR syndrome is a rare contiguous gene deletion syndrome with a greater risk of developing Wilms tumour associated with Peters' anomaly and congenital aniridia. However, co-occurrence of both anomalies was rarely reported in twins, and never in both eyes of monozygotic twins. Here, we report the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins with WAGR syndrome. [ABSTRACT FROM AUTHOR]

Background: WAGR syndrome is a rare genetic disorder characterized by a de novo deletion of 11p13 and is usually clinically associated with Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (W-A-G-R). Although the genotypic defects in WAGR syndrome have been well established. The congenital aniridia is caused, in nearly 90% of cases by mutations in the gene PAX6. In the face of congenital aniridia, it is imperative to specify whether it falls within the scope of a WAGR syndrome or if it is an isolated congenital aniridia or inherited by performing karyotype, FISH (Fluorescence In Situ Hybridization) or a CGH array for genetic counseling. Case presentation: We report here a case of genetic testing for newborn with aniridia, to detect 11p13 rearrangements, using karyotyping and CGH array to complete picture of the chromosomal deletions and breakpoints in aniridia. Results show either a loss of 3811.196 kb on chromosome 11 delimited by the bands p14.1 and p13 with formula or a loss of a 1867.287 kb on chromosome 18 fragment delimited by q21.33 and q22.1 bands, that has not been detected by karyotype analysis. Conclusions: Cytogenetics screening is a good strategy for the genetic diagnosis of aniridia and associated syndromes, allowing for a better identification of breakpoints. Our results underline the clinical importance of performing exhaustive and accurate analysis of chromosomal rearrangements for patients with aniridia, especially newborns to improve survival and quality of life for affected individuals. [ABSTRACT FROM AUTHOR]

Wilms tumor (WT) is the most common malignancy of the genitourinary system in children. Currently, the Integration of single-cell RNA sequencing (scRNA-Seq) and Bulk RNA sequencing (RNA-Seq) analysis of heterogeneity between different cell types in pediatric WT tissues could more accurately find prognostic markers, but this is lacking. RNA-Seq and clinical data related to WT were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Small nucleolar RNA host gene 15 (SNHG15) was identified as a risk signature from the TARGET dataset by using weighted gene co-expression network analysis, differentially expressed analysis and univariate Cox analysis. After that, the functional mechanisms, immunological and molecular characterization of SNHG15 were investigated at the scRNA-seq, pan-cancer, and RNA-seq levels using Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), ESTIMATE, and CIBERSORT. Based on scRNA-seq data, we identified 20 clusters in WT and annotated 10 cell types. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing M2 macrophages as hubs for intercellular communication. In addition, in vitro cellular experiments showed that siRNAs interfering with SNHG15 significantly inhibited the proliferation and migration of G401 cells and promoted the apoptosis of G401 cells compared with the control group. The effect of siRNAs interfering with SNHG15 on EMT-related protein expression was verified by Western blotting assay. Thus, our findings will improve our current understanding of the pathogenesis of WT, and they are potentially valuable in providing novel prognosis markers for the treatment of WT. [ABSTRACT FROM AUTHOR]

Three years ago, our patient, at that time a 16-month-old boy, was discovered to have bilateral kidney lesions with a giant tumor in the right kidney. Chemotherapy and bilateral nephron-sparing surgery (NSS) for Wilms tumor with nephroblastomatosis was carried out. The patient also had eye affection, including glaucoma, eye enlargement, megalocornea, severe corneal swelling and opacity, complete aniridia, and nystagmus. The diagnosis of WAGR syndrome was suspected. De novo complex chromosomal rearrangement with balanced translocation t(10,11)(p15;p13) and a pericentric inversion inv(11)(p13q12), accompanied by two adjacent 11p14.1p13 and 11p13p12 deletions, were identified. Deletions are raised through the complex molecular mechanism of two subsequent rearrangements affecting chromosomes 11 and 10. WAGR syndrome diagnosis was clinically and molecularly confirmed, highlighting the necessity of comprehensive genetic testing in patients with congenital aniridia and/or WAGR syndrome. [ABSTRACT FROM AUTHOR]

Aniridia is characterised by variable degrees of hypoplastic iris or complete absence of iris tissue and is a rare congenital disorder. Mutation in the PAX6 gene is mostly responsible for aniridia. It is associated with various ocular manifestations involving both anterior and posterior segments of the eye. A 14-year-old male patient, presented to the ophthalmology outpatient department with complaints of a gradual decrease in vision in his left eye. Upon examination, photophobia and bilateral aniridia associated with nystagmus were present in both eyes, along with a sclerally fixated intraocular lens in the right eye and a superiorly subluxated mature cataract in the left eye. Intraocular pressure was elevated in the left eye. Gonioscopy revealed rudimentary iris tissue in both eyes. Upon systemic examination, the patient was diagnosed with hydro-ureteronephrosis of the right-side, which was asymptomatic, and borderline intellectual functioning. This case highlights the unique features of WAGR syndrome (Wilm's tumour, Aniridia, Genito-urinary anomalies, Range of developmental delay) presenting with aniridia and genito-urinary conditions, along with borderline intellectual functioning without the presentation of Wilm's tumour. Cataract extraction by lens aspiration with scleral fixation of intraocular lens implantation was performed in the left eye. This study adds to the broader knowledge of the disease entity's spectrum, exploring the diagnostic challenges associated with the case and potentially influencing diagnostic criteria. It may guide future studies exploring the diverse clinical presentations of WAGR syndrome. [ABSTRACT FROM AUTHOR]

Congenital aniridia manifests with total or partial absence of the iris. The association of the disease with the PAX6 gene has been proven. Changes in the PAX6 structure lead to intrauterine pathology, visual organ malformation, malformation of master regulator proteins of organogenesis affecting various cells’ differentiation (central nervous system cells included). Such disorders result into the development of PAX6-associated syndromes with various brain malformations, neurological disorders, and systemic pathology (thyroid pathology, Wilms tumor, glucose intolerance). Isolated congenital aniridia is also accompanied by psychoneurological disorders. It can be associated with brain structures’ disorders during embryogenesis and with impact of external stress factors on the child (frequent medical checkup, surgical treatments). The psychoneurological disorders’ pathogenesis as well as congenital aniridia’s genetic mechanisms remain unclear. Thus, it is crucial to review new relevant data within the context of previously obtained information to gather full picture of the clinical signs of the disease and to improve the management of children with congenital aniridia.

Purpose: To report a case of XEN45 gel stent implantation in a pediatric patient with WAGR syndrome as a successful surgical intervention in the management of multifactorial secondary open-angle glaucoma. Observations: A 6-year-old female with a history of WAGR syndrome, bilateral congenital aniridia, pseudophakia OD and glaucoma OD, was referred for a XEN45 gel stent OD. IOP was persistently elevated at 24 mm Hg despite two glaucoma medications. Implantation of the XEN45 gel stent was performed using a transconjunctival ab externo approach. There were no significant intra-or-postoperative adverse events associated with the stent. The patient achieved good IOP-lowering control without glaucoma medications across the 18-month follow-up period. Conclusions: A XEN45 stent through a transconjunctival ab externo approach may be an effective surgical intervention in pediatric patients with secondary open-angle glaucoma associated with aniridia and aphakia.

This study investigates the distribution of PAX6-associated congenital aniridia (AN) and WAGR syndrome across Russian Federation (RF) districts while characterizing PAX6 gene variants. We contribute novel PAX6 pathogenic variants and 11p13 chromosome region rearrangements to international databases based on a cohort of 379 AN patients (295 families, 295 probands) in Russia. We detail 100 newly characterized families (129 patients) recruited from clinical practice and specialized screening studies. Our methodology involves multiplex ligase-dependent probe amplification (MLPA) analysis of the 11p13 chromosome, PAX6 gene Sanger sequencing, and karyotype analysis. We report novel findings on PAX6 gene variations, including 67 intragenic PAX6 variants and 33 chromosome deletions in the 100 newly characterized families. Our expanded sample of 295 AN families with 379 patients reveals a consistent global PAX6 variant spectrum, including CNVs (copy number variants) of the 11p13 chromosome (31%), complex rearrangements (1.4%), nonsense (25%), frameshift (18%), and splicing variants (15%). No genetic cause of AN is defined in 10 patients. The distribution of patients across the Russian Federation varies, likely due to sample completeness. This study offers the first AN epidemiological data for the RF, providing a comprehensive PAX6 variants spectrum. Based on earlier assessment of AN prevalence in the RF (1:98,943) we have revealed unexamined patients ranging from 55% to 87%, that emphases the need for increased awareness and comprehensive diagnostics in AN patient care in Russia. [ABSTRACT FROM AUTHOR]

Evolutionarily conserved genes often play critical roles in organismal physiology. Here, we describe multiple roles of a previously uncharacterized Class III metallophosphodiesterase in Drosophila, an ortholog of the MPPED1 and MPPED2 proteins expressed in the mammalian brain. dMpped, the product of CG16717, hydrolyzed phosphodiester substrates including cAMP and cGMP in a metal-dependent manner. dMpped is expressed during development and in the adult fly. RNA-seq analysis of dMppedKO flies revealed misregulation of innate immune pathways. dMppedKO flies showed a reduced lifespan, which could be restored in Dredd hypomorphs, indicating that excessive production of antimicrobial peptides contributed to reduced longevity. Elevated levels of cAMP and cGMP in the brain of dMppedKO flies was restored on neuronal expression of dMpped, with a concomitant reduction in levels of antimicrobial peptides and restoration of normal life span. We observed that dMpped is expressed in the antennal lobe in the fly brain. dMppedKO flies showed defective specific attractant perception and desiccation sensitivity, correlated with the overexpression of Obp28 and Obp59 in knock-out flies. Importantly, neuronal expression of mammalian MPPED2 restored lifespan in dMppedKO flies. This is the first description of the pleiotropic roles of an evolutionarily conserved metallophosphodiesterase that may moonlight in diverse signaling pathways in an organism. Author summary: The MPPED2 gene maps to a human genetic locus associated with the WAGR syndrome, manifesting as Wilms Tumor, genitourinary abnormalities, and mental retardation. The mammalian protein is expressed in the brain, but the function of this protein in neurons is unknown. Here we have used Drosophila to identify various functions of the fly ortholog of MPPED2. We find that this gene product is expressed in a variety of tissues and can cleave phosphodiester bonds present in cyclic nucleotides. The protein is important for optimum life span in the fly, mediated by regulating the expression of immune genes. Longevity could be rescued by neuronal expression of the mammalian ortholog. The gene product is expressed in neurons in the antennal lobe of the fly and modulates responsiveness to odorants. Therefore, this evolutionarily conserved protein has multiple roles in the physiology of an organism, either by interacting with other proteins, or cleaving natural phosphodiester bonds, and further studies in mammals are warranted. [ABSTRACT FROM AUTHOR]

Michael A Krause,1 Kelly L Trout,2 James D Lauderdale,3 Peter A Netland1 1Department of Ophthalmology, University of Virginia School of Medicine, Charlottesville, VA, USA; 2International WAGR Syndrome Association, Montgomery Village, MD, USA; 3Department of Cellular Biology, University of Georgia, Athens, GA, USACorrespondence: Peter A Netland, Department of Ophthalmology, University of Virginia School of Medicine, 1300 Jefferson Park Avenue, P.O. Box 800715, Charlottesville, VA, 22908-0715, USA, Tel +1 434-982-1086, Email pnetland@virginia.eduPurpose: Our purpose was to evaluate visual acuity in aniridia subjects and the more severely affected phenotype in WAGR syndrome subjects, and to assess potential impact on visual function.Materials and Methods: This was a retrospective comparative study of 25 aniridia subjects with nonsense mutations of PAX6 (50 eyes) and 25 WAGR syndrome subjects with large deletion mutations involving PAX6 (50 eyes). Aniridia subjects were age- and gender-matched with WAGR syndrome subjects in the Coordination of Rare Diseases at Sanford (CoRDS) database. Best-corrected ETDRS visual acuity measurements were converted to LogMAR visual acuity values, which were used to perform statistical analyses.Results: The age and gender distribution of the subjects was not statistically significantly different. The mean LogMAR values in aniridia and WAGR syndrome subjects were 0.95± 0.53 and 1.51± 0.99, respectively (P< 0.001). In the better-seeing eye, mean LogMAR values were 0.78± 0.15 in aniridia subjects and 1.40± 0.88 in WAGR syndrome subjects (P=0.001). The mean LogMAR values for the better-seeing eye corresponded to Snellen visual acuity of 20/125 in aniridia subjects and 20/500 in WAGR syndrome subjects. This average visual acuity was worse than the threshold for profound visual impairment (WHO criteria) and legal blindness (AAO criteria) in WAGR syndrome but not in aniridia subjects. In analysis of both eyes, the visual efficiency was 34% in aniridia subjects and 2% in WAGR syndrome subjects.Conclusion: Visual acuity was significantly worse in WAGR subjects with multi-gene deletion mutations compared with aniridia subjects with nonsense mutations, which corresponded to differences in standard visual function thresholds. Our results suggest that visual acuity may indicate severity of ocular involvement and variability of phenotype in aniridia and WAGR syndrome.Keywords: aniridia, WAGR syndrome, WAGR spectrum, PAX6, visual impairment, blindness

Aniridia is an autosomal dominant congenital malformation associated with mutations in the PAX6 gene. It can be associated with deletion in the contiguous WT1 gene, leading to WAGR syndrome, characterized by Wilm tumor, aniridia, genitourinary anomalies, and mental retardation. Persistent fetal vasculature is a developmental malformation caused by incomplete regression of hyaloid vasculature. Most cases of persistent fetal vasculature occur sporadically; however, some inherited forms are described. We report a case of genetically confirmed WAGR associated with congenital cataract and persistent fetal vasculature.▪ [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells exhibit unrestrained cell growth and proliferation owing to tumor-specific characteristics such as altered metabolism. Tumor cells vary metabolic pathways to meet their needs for rapid cell growth. In this review, we focus particularly on lipid metabolism in embryonal tumors with deregulated MYCN function, specifically neuroblastoma, retinoblastoma, Wilms tumor, medulloblastoma, and rhabdomyosarcoma. We also discuss whether we can target lipid metabolism to restrict tumor cell growth and proliferation. Tumor cells reprogram their metabolism, including glucose, glutamine, nucleotide, lipid, and amino acids to meet their enhanced energy demands, redox balance, and requirement of biosynthetic substrates for uncontrolled cell proliferation. Altered lipid metabolism in cancer provides lipids for rapid membrane biogenesis, generates the energy required for unrestricted cell proliferation, and some of the lipids act as signaling pathway mediators. In this review, we focus on the role of lipid metabolism in embryonal neoplasms with MYCN dysregulation. We specifically review lipid metabolic reactions in neuroblastoma, retinoblastoma, medulloblastoma, Wilms tumor, and rhabdomyosarcoma and the possibility of targeting lipid metabolism. Additionally, the regulation of lipid metabolism by the MYCN oncogene is discussed. [ABSTRACT FROM AUTHOR]

Three years ago, our patient, at that time a 16-month-old boy, was discovered to have bilateral kidney lesions with a giant tumor in the right kidney. Chemotherapy and bilateral nephron-sparing surgery (NSS) for Wilms tumor with nephroblastomatosis was carried out. The patient also had eye affection, including glaucoma, eye enlargement, megalocornea, severe corneal swelling and opacity, complete aniridia, and nystagmus. The diagnosis of WAGR syndrome was suspected. De novo complex chromosomal rearrangement with balanced translocation t(10,11)(p15;p13) and a pericentric inversion inv(11)(p13q12), accompanied by two adjacent 11p14.1p13 and 11p13p12 deletions, were identified. Deletions are raised through the complex molecular mechanism of two subsequent rearrangements affecting chromosomes 11 and 10. WAGR syndrome diagnosis was clinically and molecularly confirmed, highlighting the necessity of comprehensive genetic testing in patients with congenital aniridia and/or WAGR syndrome.

The deletion of chromosome 11p13 involving the WT1 and PAX6 genes has been shown to cause WAGR syndrome (OMIM #194072), a rare genetic disorder that features Wilms' tumor, aniridia, genitourinary anomalies, as well as mental retardation. In this study, we expand the genotypic and phenotypic spectrum of WAGR syndrome by reporting on six patients from six unrelated families with different de novo deletions located on chromosome 11p13. Very rare phenotypes of lens automated absorption and lens thinning were detected in four of the six patients. We assessed the involvement of the ARL14EP gene in patients with and without severe lens abnormalities and found that its deletion may worsen the lens abnormalities in these patients. [ABSTRACT FROM AUTHOR]

2020, 157 (01): 23 6 Justice E. D., Barnum S. J., Kidd T. The WAGR syndrome gene PRRG4 is a functional homologue of the commissureless axon guidance gene. [5] We describe here a patient harboring the largest germline heterozygous deletion reported so far, including, among others, PSS and WAGR syndrome loci (MIM #601224 and MIM #194072). Keywords: Potocki-Schaffer syndrome; WAGR syndrome; contiguous gene deletion; array-CGH; oligohydramnios EN Potocki-Schaffer syndrome WAGR syndrome contiguous gene deletion array-CGH oligohydramnios 274 278 5 09/07/22 20220701 NES 220701 Conflict of Interest None declared. WAGR syndrome, array-CGH, Potocki-Schaffer syndrome, contiguous gene deletion, oligohydramnios. [Extracted from the article]

Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome is a contiguous gene deletion syndrome caused by a de novo deletion including the 11p13 region. Although autism spectrum disorder (ASD) is frequently observed in patients with WAGR syndrome, few reports have comprehensively described its characteristics. We herein present the detailed neuropsychological and neurophysiological findings of a patient with WAGR syndrome complicated with severe psychomotor developmental delay and ASD. The patient is presently a 6-year-old boy. Microarray analysis revealed a 7.1 Mb loss at 11p14.3-p13 and a 9.3 Mb loss at 11p13-p12, which encompassed the PAX6 , WT1 , and PRRG4 genes. His behavioral features were characteristic even among the ASD population: severe hypoesthesia to touch, pain, and temperature in addition to remarkable sensory seeking posing a high risk of serious accident. Sensory Profile analysis objectively identified a strong preference for sensory stimulation. Furthermore, his somatosensory evoked potential (SSEP) showed a mild delay in central conduction time, suggesting partial brain stem dysfunction-induced hypoalgesia. This first attempt to characterize sensory dysfunction using Sensory Profile and SSEP in WAGR syndrome may contribute to understanding its neuropsychological features and improve the quality of rehabilitation and socioeducational support in affected children. [ABSTRACT FROM AUTHOR]

The article presents a case study of 14-year-old girl initially diagnosed with WAGR syndrome, later developing multiple exostoses, indicative of Potocki-Shaffer syndrome (PSS). It is reported that genetic testing revealed a 26.4 Mb deletion on chromosome 11, indicating a combination of WAGR and PSS. It further underscores the need for long-term observation and genetic testing in complex syndromes.

Intravascular extension of Wilms tumor (WT) can occur in approximately 4-10% of patients. In general, it does not cause any clinical problems because most of these tumors are small. Although there is no standard treatment currently, preoperative chemotherapy and delayed nephrectomy is generally recommended for children with WT accompanied by tumor thrombus. We report a rare case of WT, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome in a boy who also had a huge inferior vena cava thrombus, 7 cm length. The prevalence of bilateral WT and tumor thrombus in WAGR has not been identified. The patient was successfully treated with neoadjuvant chemotherapy to decrease the size of the tumor thrombus with WT and delayed nephrectomy following chemotherapy without any invasive intervention and did not show complications.

Abstract WAGR 11p13 deletion syndrome is associated with abnormalities including (W) ilms tumor, (A) niridia, (G) enitourinary abnormalities, and growth and mental (R) etardation (WAGR). Potocki–Schaffer syndrome is a contiguous gene syndrome associated with deletions in 11p11.2, principal features of which are multiple exostoses, parietal foramina development delay, mental retardation, and facial dysmorphism. In some cases, males may have enlarged anterior fontanels and genital abnormalities. Each of these syndromes is very rare. Here we report a patient with both WAGR and Potocki–Shaffer syndromes who presented with aniridia, nystagmus, macular dysplasia, enlarged anterior fontanel, mental retardation, ptosis, low-set ears, micrognathia, and atrial septal defect at 6 months old. SNP array revealed a large (26.25 Mb)deletion: arr[hg19]11p15.1p11.2(18742043–44991839)× 1. Genetic testing allowed for diagnosis of this patient at a very young age. In addition to the postnatal phenotype of the patient, we found one prenatal symptom of these syndromes is oligohydramnios, which when present might indicate advanced prenatal diagnosis. This made the possibility of prenatal diagnosis for these syndromes.

Background: Although hypotension is a life-threatening complication of nephrectomy in children, risk factors for its development remain unknown. We evaluated the incidence, clinical course, and associated risk factors of pediatric post-nephrectomy hypotension in an observational study. Methods: This retrospective observational study included the clinical data of children who underwent nephrectomy in our center between 2002 and 2020. Patients undergoing nephrectomy at kidney transplantation and those who developed hypotension before nephrectomy were excluded. Results: The study included 55 nephrectomies in 51 patients, including 42 unilateral, 4 two-stage bilateral, and 5 simultaneous bilateral nephrectomies. The diagnoses were isolated Wilms tumor, neuroblastoma, congenital nephrotic syndrome, Denys-Drash syndrome, WAGR (Wilms tumor, aniridia, genitourinary malformations, and mental retardation) syndrome, and autosomal recessive polycystic kidney disease in 24, 10, 9, 6, 1, and 1 patient, respectively. Post-nephrectomy hypotension developed in 11 (20%) patients. Two patients (3.6%) had persistent hypotension; both had their kidneys resected, and one patient (1.8%) died. Male sex, kidney disease, resection of both kidneys, low estimated glomerular filtration rate, increased left ventricular posterior wall thickness in diastole, hypertension before nephrectomy, antihypertensive use, hyperreninemia, and hyperaldosteronism were significantly associated with post-nephrectomy hypotension. Multivariate logistic regression analysis revealed that hypertension before nephrectomy was the only significant risk factor for post-nephrectomy hypotension (P = 0.04). Conclusions: Hypertension before nephrectomy is a significant risk factor for pediatric post-nephrectomy hypotension. Life-threatening hypotension, which might occur after bilateral nephrectomy in infants, should be considered, especially in children with higher risks. [ABSTRACT FROM AUTHOR]

WAGR 11p13 deletion syndrome is associated with abnormalities including (W) ilms tumor, (A) niridia, (G) enitourinary abnormalities, and growth and mental (R) etardation (WAGR). Potocki–Schaffer syndrome is a contiguous gene syndrome associated with deletions in 11p11.2, principal features of which are multiple exostoses, parietal foramina development delay, mental retardation, and facial dysmorphism. In some cases, males may have enlarged anterior fontanels and genital abnormalities. Each of these syndromes is very rare. Here we report a patient with both WAGR and Potocki–Shaffer syndromes who presented with aniridia, nystagmus, macular dysplasia, enlarged anterior fontanel, mental retardation, ptosis, low-set ears, micrognathia, and atrial septal defect at 6 months old. SNP array revealed a large (26.25 Mb)deletion: arr[hg19]11p15.1p11.2(18742043–44991839)× 1. Genetic testing allowed for diagnosis of this patient at a very young age. In addition to the postnatal phenotype of the patient, we found one prenatal symptom of these syndromes is oligohydramnios, which when present might indicate advanced prenatal diagnosis. This made the possibility of prenatal diagnosis for these syndromes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the correlation of cerebrospinal fluid total protein and serum neutrophil-to-lymphocyte ratio with the clinical outcomes and the various clinical and electrophysiological variants of Guillain-Barre syndrome., Study Design: Cross-sectional study. Place and Duration of the Study: Department of Neurology, Mayo Hospital and King Edward Medical University, Lahore, Pakistan, from November 2022 to April 2023., Methodology: Fourty-six Guillain-Barre syndrome patients, aged 12-70 years, were included in the study diagnosed by using the Brighton's criteria. Functional disability and respiratory insufficiency were assessed by using the modified Hughes disability score and the Erasmus Guillain-Barre syndrome respiratory insufficiency score, respectively. Serum neutrophil-to-lymphocyte ratio and cerebrospinal fluid total protein were calculated for each patient at the time of admission., Results: Axonal variants had a higher mean neutrophil-to-lymphocyte ratio (5.29 ± 4.38) than demyelinating variants (4.71 ± 3.4) and Miller-Fischer syndrome (3 ± 2.828). This ratio was positively correlated with the modified Hughes's disability score (r = 0.790, p = 0.001) and the Erasmus Guillain-Barre syndrome respiratory insufficiency score (r = 0.936, p = 0.002). Mean cerebrospinal fluid total protein was higher for demyelinating (218 ± 136 mg/dl) than axonal variants (86 ± 56 mg/dl) and Miller-Fischer syndrome (34 ± 21 mg/dl). However, higher modified Hughes disability score (4-6) (r = 0.020, p = 0.117) and a high Erasmus Guillain-Barre syndrome respiratory insufficiency score (5-7) (r = 0.115, p = 0.302) did not significantly affect mean cerebrospinal fluid total proteins., Conclusion: Serum neutrophil-to-lymphocyte ratio can be regarded as a reliable biomarker to assess disease severity and clinical outcome in Guillain-Barre syndrome. Cerebrospinal fluid total protein is a poor predictor of the prognosis and severity of Guillain-Barre syndrome., Key Words: Guillain-Barre syndrome (GBS), Clinical outcome, Cerebrospinal fluid total protein (CSF-TP), Neutrophil-to-lymphocytic ratio (NLR), Prognostic biomarker.

Background: Wilms tumor, aniridia, genitourinary anomalies and mental retardation (WAGR) syndrome is a rare genetic disorder caused by heterozygous deletions of WT1 and PAX6 at chromosome 11p13. Deletion of BDNF is known eto be associated with hyperphagia and obesity in both humans and animal models; however, neuroendocrine and epigenetic profiles of individuals with WAGR syndrome remain to be determined. Case presentation: We report a 5-year-old girl with the typical phenotype of WAGR syndrome. She showed profound delays in physical growth, motor and cognitive development without signs of obesity. Array comparative genome hybridization (CGH) revealed that she carried a 14.4 Mb deletion at 11p14.3p12, encompassing the WT1, PAX6 and BDNF genes. She experienced recurrent hypoglycemic episodes at 5 years of age. Insulin tolerance and hormonal loading tests showed normal hypothalamic responses to the hypoglycemic condition and other stimulations. Methylation analysis for freshly prepared DNA from peripheral lymphocytes using the pyro-sequencing-based system showed normal patterns of methylation at known imprinting control regions. Conclusions: Children with WAGR syndrome may manifest profound delay in postnatal growth through unknown mechanisms. Epigenetic factors and growth-associated genes in WAGR syndrome remain to be characterized. [ABSTRACT FROM AUTHOR]

Congenital aniridia is a rare, bilateral condition associated with foveal hypoplasia, nystagmus, cataract, glaucoma, keratopathy, and dry eye. Aniridic fibrosis syndrome is a newly recognized clinical entity characterized by progressive retrocorneal, cyclitic, or retrolenticular fibrosis which can lead to corneal endothelial decompensation, hypotony, and retinal detachment. A 6-year-old male presented with WAGR syndrome. At presentation he had mental retardation, nystagmus, bilateral rudimentary iris, and bilateral posterior polar cataract. Cataract extraction and implantation of an aniridia intraocular lens (IOL) was performed in the right eye. Glaucoma developed in the right eye approximately 2 months after cataract surgery. An Ahmed glaucoma valve was implanted in the right eye and prophylactic goniotomy was performed in the left eye. Nine months after glaucoma surgeries aniridia-associated keratopathy (AAK) was observed in both eyes (predominantly in the right eye). Keratopathy progressed during follow-up. At the 6th year follow-up aniridic fibrosis syndrome was detected in the right eye, with retrocorneal fibrotic membrane formation, inferior dislocation of the IOL, and endothelial decompensation. During the 6-years follow-up, intraocular pressure was controlled with 2 medications in the right and without medication in the left eye. The management of aniridia is often quite difficult because of the complex involvement of ocular structures. Although satisfactory results can be obtained with surgery for cataract and glaucoma, progression of AAK and development of aniridic fibrosis syndrome (especially in eyes with intraocular hardware) are the obstacles for good visual outcome. This is the first case of aniridic fibrosis syndrome reported from Turkey. [ABSTRACT FROM AUTHOR]

WAGR syndrome is characterized by Wilm’s tumor, aniridia, genitourinary abnormalities and intellectual disabilities. WAGR is caused by a chromosomal deletion that includes the PAX6, WT1 and PRRG4 genes. PRRG4 is proposed to contribute to the autistic symptoms of WAGR syndrome, but the molecular function of PRRG4 genes remains unknown. The Drosophila commissureless (comm) gene encodes a short transmembrane protein characterized by PY motifs, features that are shared by the PRRG4 protein. Comm intercepts the Robo axon guidance receptor in the ER/Golgi and targets Robo for degradation, allowing commissural axons to cross the CNS midline. Expression of human Robo1 in the fly CNS increases midline crossing and this was enhanced by co-expression of PRRG4, but not CYYR, Shisa or the yeast Rcr genes. In cell culture experiments, PRRG4 could re-localize hRobo1 from the cell surface, suggesting that PRRG4 is a functional homologue of Comm. Comm is required for axon guidance and synapse formation in the fly, so PRRG4 could contribute to the autistic symptoms of WAGR by disturbing either of these processes in the developing human brain. [ABSTRACT FROM AUTHOR]

Wilm's tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome, a rare genetic disorder, is caused by the loss of 11p13 region including PAX6 and WT1. We report novel findings in a 28-month-old boy with aniridia, Wilm's tumor, congenital hypothyroidism, and sublingual thyroid ectopia. He was found to have a mosaic 5.28 Mb interstitial deletion of chromosome 11p13 deleting PAX6 and WT1. In order to clarify the mechanism underlying his thyroid dysgenesis, sequence analysis of candidate thyroid developmental genes was performed. We identified a FOXE1: c.532_537delGCCGCC p.(Ala178_Ala179del) variant that predisposes to thyroid ectopia. Taken together, this is the first report of mosaic 11p13 deletion in association with thyroid dysgenesis. We also propose a model of complex interactions of different genetic variants for this particular phenotype in the present patient. [ABSTRACT FROM AUTHOR]

Wilms tumour is named after Max Wilms. It is an embryonal tumour derived from the metanephros. It is the commonest childhood renal tumour and the third commonest paediatric malignancy. Synchronous bilateral Wilms tumours (BWT) represent 4-7% of all Wilms tumours (WT) and present at a younger age than unilateral Wilms tumours. At least 10% of synchronous BWTs have unfavourable histology, and up to 22% are associated with genitourinary abnormalities, aniridia, WAGR syndrome, Denys-Drash Syndrome, hemihypertrophy, or one of the other overgrowth syndromes. The long-term disease-free survival (DFS) rate for patients with unilateral Wilms' tumours is approaching 90%, and is around 70% for those with metastatic disease. For both synchronous and metachronous Wilms tumours the prognosis is less favourable with reported cure rates approaching 80% in the best centres and lower in resource poor settings. There is potential for a reduced quality of life due to renal insufficiency and the possible need for renal transplantation. The major clinical challenge in BWTs is preservation of functioning renal tissue using nephron sparing surgical techniques, while achieving cure with minimum therapy-related morbidity. Mortality is generally associated with progressive disease of anaplastic tumours. Chemotherapy followed by nephron sparing surgery has been able, in most cases, to eradicate the tumour while preserving renal function. Radiotherapy has largely been avoided because of fears of long term radiation injury to the residual functioning renal mass. Patient selection, appropriate pre- and post-operative chemotherapy and skilled surgical techniques all contribute to excellent outcomes where these are achievable. [ABSTRACT FROM AUTHOR]

Chromosomal deletions at 11p13 are a frequent cause of congenital Aniridia, a rare pan-ocular genetic disease, and of WAGR syndrome, accounting up to 30% of cases. First-tier genetic testing for newborn with aniridia, to detect 11p13 rearrangements, includes Multiplex Ligation-dependent Probe Amplification (MLPA) and karyotyping. However, neither of these approaches allow obtaining a complete picture of the high complexity of chromosomal deletions and breakpoints in aniridia. Here, we report the development and validation of a customized targeted array-based comparative genomic hybridization, so called WAGR-array, for comprehensive high-resolution analysis of CNV in the WAGR locus. Our approach increased the detection rate in a Spanish cohort of 38 patients with aniridia, WAGR syndrome and other related ocular malformations, allowing to characterize four undiagnosed aniridia cases, and to confirm MLPA findings in four additional patients. For all patients, breakpoints were accurately established and a contiguous deletion syndrome, involving a large number of genes, was identified in three patients. Moreover, we identified novel microdeletions affecting 3' PAX6 regulatory regions in three families with isolated aniridia. This tool represents a good strategy for the genetic diagnosis of aniridia and associated syndromes, allowing for a more accurate CNVs detection, as well as a better delineation of breakpoints. Our results underline the clinical importance of performing exhaustive and accurate analysis of chromosomal rearrangements for patients with aniridia, especially newborns and those without defects in PAX6 after diagnostic screening. [ABSTRACT FROM AUTHOR]

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Congenital aniridia is a rare ocular malformation that presents with severe hypoplasia of the iris and various ocular manifestations. Most cases of congenital aniridia are known to be related to mutations in the paired box gene-6 (PAX6), which is an essential gene in eye development. Herein, we report a familial case of autosomal dominant congenital aniridia with four affected members in 3 consecutive generations and describe the detailed ophthalmologic findings for one of these members. As expected, mutational analysis revealed a nonsense mutation (p.Ser122*) in the PAX6 gene. Thus, our findings reiterate the importance of PAX6 mutations in congenital aniridia.

Congenital aniridia is a rare ocular malformation that presents with severe hypoplasia of the iris and various ocular manifestations. Most cases of congenital aniridia are known to be related to mutations in the paired box gene-6 (PAX6), which is an essential gene in eye development. Herein, we report a familial case of autosomal dominant congenital aniridia with four affected members in 3 consecutive generations and describe the detailed ophthalmologic findings for one of these members. As expected, mutational analysis revealed a nonsense mutation (p.Ser122*) in the PAX6 gene. Thus, our findings reiterate the importance of PAX6 mutations in congenital aniridia. [ABSTRACT FROM AUTHOR]

WAGR syndrome is caused by an 11p13 deletion and includes Wilms' tumor, aniridia, genitourinary anomalies and mental retardation. We encountered a case of a dysgerminoma originating in an ectopic ovary in a woman with WAGR syndrome. Our patient was a 24-year-old nulliparous woman who was diagnosed with WAGR syndrome. The patient had undergone left nephrectomy for a Wilms' tumor and postoperative chemotherapy at the age of 7 months. She also had a history of glaucoma surgery in both eyes, and was followed up at the Department of Pediatrics for diabetes mellitus, hypertension, liver dysfunction and hyperuricemia. The patient was investigated for oliguria and had elevated levels of blood urea nitrogen (45 mg/dl) and creatinine (5.4 mg/dl); she was admitted to the hospital with acute renal failure and a computed tomography scan revealed a pelvic tumor with a long axis of 10 cm that was obstructing the right ureter. Following insertion of a ureteral stent, the tumor was removed. The tumor had developed in the retroperitoneal space independent of the ovaries. The right adnexa were normal. The tumor was histopathologically diagnosed as dysgerminoma. Follicles were found in part of the tumor; it was thus hypothesized that the tumor developed from an ectopic ovary. The patient was administered etoposide after surgery, and has been recurrence-free for 4 years since treatment. [ABSTRACT FROM AUTHOR]

In rodent studies, paired box 6 ( PAX6) appears to play an important role in the development of the pineal, the primary source of the circadian regulating hormone, melatonin. Pineal hypoplasia has been previously reported in patients with PAX6 haploinsufficiency (+/−); however, pineal measurement, melatonin concentrations and sleep quality have not been reported. This cross-sectional descriptive study examined pineal volume, melatonin secretion and sleep disturbance in 37 patients with PAX6+/− (age 15.3 ± 9.9 years) and 17 healthy controls (16.0 ± 7.2 years), within an inpatient setting at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, USA. Pineal volume was evaluated by magnetic resonance imaging. Diurnal serum cortisol, serum melatonin and urine 6-sulphatoxymelatonin concentrations were measured by enzyme-linked immunosorbent assay. The Child Sleep Habits Questionnaire was administered for patients <13 years old. Pineal volume was fivefold lower in PAX6+/− versus controls (mean ± SD: 25 ± 15 versus 129 ± 50 μL, P < 0.001). Midnight serum cortisol was similar in PAX6+/− versus controls ( P = 0.14). Midnight serum melatonin was > twofold lower in PAX6+/− versus controls [median (25th-75th): 28 (22-42) versus 71 (46-88) pg mL−1, P < 0.001]. First morning void urinary 6-sulphatoxymelatonin was fourfold lower in PAX6+/− versus controls [11 (6-26) versus 45 (34-61) ng mg−1 Cr, P = 0.001]. Child Sleep Habits Questionnaire score was higher in PAX6+/− versus controls (48 ± 6 versus 41 ± 5, P = 0.03). The current findings suggest that PAX6+/− is associated with smaller pineal size, lower melatonin secretion and greater parental report of sleep disturbances in children. Further studies are needed to explore the potential use of melatonin replacement for improving sleep quality in patients with PAX6+/−. [ABSTRACT FROM AUTHOR]

A correction to the article "Risk factors for post-nephrectomy hypotension in pediatric patients" in the May 2021 issue is presented.