DOCSLIB.ORG

WAGR Syndrome: Clinical Features and Guidelines for Management

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WAGR Syndrome: Clinical Features and Guidelines for Management WAGR syndrome: clinical features and guidelines for management Kelly Trout, BSN, RN International WAGR Syndrome Association 2020 Introduction WAGR syndrome is a rare multiple congenital-anomaly syndrome caused by interstitial deletion of the distal portion of chromosome 11p13. Deletion size varies between individuals from 1 million to 26.5 million base pairs, with an average of 11 million base pairs. Variability in size of the genetic deletion is thought to account for the variable phenotype. WAGR is an acronym for the most prominent features: W is for Wilms tumor, A for aniridia, G for genitourinary anomalies, and R for range of developmental delays. Wilms tumor and genital anomalies are caused by deletion of the WT1 tumor-suppressor gene, and aniridia is caused by deletion of the PAX6 ocular development gene. Developmental delays are presumed to be the result of deletion of as yet unidentified genes in the region. Most cases are identified by chromosome studies of children with isolated aniridia and are due to de novo deletions, although a few familial translocations have been reported. Individuals with WAGR syndrome have a high risk for development of Wilms tumor and late-onset renal failure, as well as a variety of additional associated conditions. Diagnosis ● Most cases of WAGR syndrome are identified in infants with isolated aniridia, 30% of whom will be positive for the characteristic deletion (11p13) ● In rare cases, aniridia may not be present. Children with Wilms tumor and genital anomalies may also warrant genetic testing ● Rare: balanced translocation in unaffected parent, Mosaic deletions ● Genetic testing ○ May begin with lymphocyte high-resolution chromosome study (at least 550 bands) ○ If the chromosomes are normal, then additional fluorescent in situ hybridization (FISH) studies should be done to identify deletion of the PAX6 gene (aniridia) and WT1 gene (Wilms tumor) ○ Array comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) may also be used to investigate deletion of clinically significant genes BDNF, EXT2, and ALX4 Clinical features and management There is no cure for WAGR syndrome. However, children with WAGR syndrome benefit from early medical support and developmental interventions, including physical, occupational, and speech therapies. Special educational services are also beneficial. Life expectancy in WAGR syndrome has not been studied, but early detection and prompt treatment of life-limiting conditions such as Wilms tumor and end stage renal failure can improve the long-term prognosis. WAGR.ORG Wilms Tumor ● Most common type of renal cancer in children ● Occurs in up to 50% of children with WAGR syndrome, most often between the ages of 1-3 years ● In rare cases may occur after age 8, and has been reported as late as age 19 ● Surveillance should begin at birth/diagnosis of WAGR syndrome with abdominal ultrasound every 3 months until age 8. After age 8, ultrasounds may continue at less frequent intervals, along with periodic abdominal palpation and assessment for hypertension and hematuria ● Nephrogenic Rests/nephroblastomatosis are common in children with WAGR syndrome. Monitor closely for malignant transformation. In some cases, these lesions may require treatment with surgery and/or chemotherapy ● Treatment ○ Refer to Hematology/Oncology Aniridia ● Iris hypoplasia ● Artificial iris implant ● Visual acuity is generally in the ○ Associated with increased incidence 20/100 to 20/200 range, but may be of glaucoma significantly decreased by any of the following ● Cataract ○ Microphthalmia ○ Occurs in 50-85% ○ Hypoplasia of the optic nerve, ○ Treatment macula, or fovea ■ Removal should be avoided ○ Nystagmus unless vision is significantly ○ Amblyopia obstructed ○ Strabismus ■ Surgery potentially more complex ○ Photophobia due to ○ Ptosis ● Tunica vasculosa lentis ○ Fragile cornea ● Capsular pseudoexfoliation ■ Avoid use of contact lenses ● Lens subluxation or when possible dislocation ■ Use preservative-free ● Fragile anterior capsule eyedrops when possible ■ Treat conjunctivitis promptly ● Surgical intervention should be minimized to avoid complications ○ Aniridia fibrosis syndrome ○ Macular edema ○ Progression of aniridia-associated keratopathy ○ Glaucoma WAGR.ORG Aniridia (cont.) ● Glaucoma ● Aniridic-associated Keratopathy ○ Occurs in 50% by age 8. Risk ○ Progressive opacification of the cornea increases with age ○ Occurs in more than 90% ○ Increased corneal thickness is ○ Multiple causes including limbal cell common deficiency, abnormal tear film ○ Exam under anesthesia may be ○ Exacerbated by injury to the cornea: necessary in young children infection, irritation, surgery ○ Treatment ○ Often begins in the first decade of life, ■ Use preservative-free medication but may not affect vision until adulthood when possible ○ Treatment ■ Surgical interventions include ■ Preservative-free, phosphate-free ● Goniotomy (may be lubricant drops considered in young infants ● Hyaluronic acid, semifluorinated with aniridia and glaucoma) alkanes, dexpanthenol ointment ● Trabeculotomy, at night trabeculectomy, and ■ Warm compresses and lid massage trabeculectomy with ■ Punctal plugs mitomycin C ■ Low-dose Cyclosporine A eye drops ● Glaucoma drainage devices ■ Autologous serum or plasma eye (Baerveldt, Ahmed, or Molteno drops tube shunts) ■ Amniotic membrane extract eye ● Laser and cyclodestructive drops or patch procedures are not useful in ■ Avoid use of VEGF antagonist eye aniridia. These procedures are drops associated with severe ■ Cornea/limbal stem cell transplant inflammatory response, lens ■ Boston Keratoprosthesis (K-Pro) subluxation, and acceleration of presenile cataracts WAGR.ORG Genitourinary Anomalies ● Males ● Ambiguous genitalia ○ Cryptorchidism ● Duplicated or ectopic ureter ○ Hypospadias ● Hypoplastic or horseshoe kidney ○ Micropenis ● Unilateral renal agenesis ○ Hypoplastic scrotum ● Renal cysts ● Females ● Treatment ○ Streak ovaries ○ Refer to Urology, Gynecology ■ Occur in XX females with WAGR syndrome ■ Rare cases of gonadoblastoma reported ■ Monitor with pelvic ultrasound or MRI and/or laboratory tests ○ Malformations of the uterus, fallopian tubes, vagina Range of Developmental Delay Auditory and Sensory Processing Disorders ● May be mild to severe. Mild to ● Auditory Processing Disorder occurs in moderate intellectual disability is more than 90% most common (IQ 50 to 70) ○ Treatment ● Some individuals with normal/near- ■ Refer to Audiology, Speech therapy normal IQ ● Sensory Processing Disorder mild to severe ● Treatment ○ Treatment ○ Refer to Early Intervention ■ Refer to Occupational therapy Services BDNF Gene Deletion ● Haploinsufficiency of Brain-Derived ● Associated with (cont.) Neurotrophic Factor ○ Decreased behavioral response to pain ● Occurs in 50% ■ May not display discomfort even ● Associated with with significant illness or injury ○ Obesity ■ May require careful observation for ○ Hyperphagia signs of illness or injury ■ May involve severe food- ○ Decreased cognition seeking behaviors ● Treatment ■ May require strict control of ○ Refer to Dietician access to food WAGR.ORG Behavioral and Psychiatric Disorders Cardiopulmonary Abnormalities ● Anxiety Disorder ● Congenital defects ● Attention-Deficit Hyperactivity ○ Patent foramen ovale Disorder (ADHD) ○ Atrial or Ventricular septal defects ● Autism ○ Valvular hypoplasia ○ A few individuals meet criteria for ○ Patent ductus arteriosus diagnosis of Autism ○ Pulmonary hypertension ○ Autistic-like behaviors are more ○ Tetralogy of Fallot common and may reflect a ● Cardiomyopathy combination of intellectual ○ May occur in patients treated with disability, vision impairment, doxorubicin for Wilms tumor Auditory/Sensory Processing ○ Requires lifelong surveillance Disorder, and/or Anxiety Disorder ● Tracheomalacia, laryngomalacia, ○ Accurate diagnosis is important to bronchomalacia effective treatment ● Recurrent pneumonia ● Depression ● Obstructive sleep apnea ● Obsessive-Compulsive Disorder ● Treatment ● Tantrums, “Meltdowns,” Aggression ○ Refer to Cardiology ● Treatment ○ Refer to Pulmonology/Sleep specialist ○ Refer to Neuropsychiatry if available. Team approach to diagnosis may be most effective Chronic Kidney Disease Head, Ears, Nose, Throat ● Focal Segmental Glomerulosclerosis ● Enlarged parietal foramina (FSGS) ● Low-set ears, pinna abnormalities ● Occurs in 60% ● Enlarged tonsils and/or adenoids ● Symptoms ○ Tonsillectomy/adenoidectomy ○ Hypertension common ○ Proteinuria ● Recurrent otitis media ○ Hypertriglyceridemia ○ Tympanostomy tube placement ● Treatment common ○ Refer to Nephrology ● Recurrent sinusitis ○ Early diagnosis and aggressive ● High-arched palate, cleft palate treatment with ACE-inhibitor ● Narrowing of the pharynx medication may slow progression, ● Micrognathia sometimes for many years ● Small, missing, misshapen teeth, dental ○ Dialysis or renal transplant malocclusion, delayed loss of primary teeth ● Hearing impairment (sensorineural) ● Abnormal brainstem response or abnormal Auditory Evoked Potential ○ Occurs in 50% ● Treatment ○ Refer to Audiology, ENT, Dentist WAGR.ORG Gastrointestinal Abnormalities Metabolic and Endocrine Abnormalities ● Acute or chronic pancreatitis ● Early onset obesity ○ Risk increased if ○ Investigate for BDNF gene deletion hypertriglyceridemia present ● Insulin resistance ○ Propofol may increase risk of ● Diabetes acute pancreatitis ● Dyslipidemia ● Gastroesophageal Reflux Disease ● Precocious puberty (GERD) ● Treatment ● Chronic
Load more

Recommended publications
  • MECHANISMS in ENDOCRINOLOGY: Novel Genetic Causes of Short Stature
    J M Wit and others Genetics of short stature 174:4 R145–R173 Review MECHANISMS IN ENDOCRINOLOGY Novel genetic causes of short stature 1 1 2 2 Jan M Wit , Wilma Oostdijk , Monique Losekoot , Hermine A van Duyvenvoorde , Correspondence Claudia A L Ruivenkamp2 and Sarina G Kant2 should be addressed to J M Wit Departments of 1Paediatrics and 2Clinical Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Email The Netherlands [email protected] Abstract The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification centred on the epiphyseal growth plate. We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature. Many novel causes of GH deficiency (GHD) as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFkB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T3/T4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH, and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature.
    [Show full text]
  • Frasier Syndrome: a Cause of Focal Segmental Glomerulosclerosis in a 46,XX Female
    BRIEF COMMUNICATIONS J Am Soc Nephrol 10: 2215–2218, 1999 Frasier Syndrome: A Cause of Focal Segmental Glomerulosclerosis in a 46,XX Female LAURIE DEMMER,* WILLIAM PRIMACK,*† VALERIE LOIK,‡ ROSALIND BROWN,* NICOLE THERVILLE,§ and KEN MCELREAVEY§ *Department of Pediatrics, University of Massachusetts Memorial Health Care, Worcester, Massachusetts; †Fallon Clinic, Worcester, Massachusetts; ‡Department of Obstetrics & Gynecology, Baystate Medical Center, Springfield, Massachusetts; and §Department of Human Immunogenetics, Institut Pasteur, Paris, France. Abstract. The description of Frasier syndrome until now has diagnosis of Frasier syndrome with 46,XY gonadal dysgenesis, been restricted to XY females with gonadal dysgenesis, pro- whereas her sister has progressive glomerulopathy but a 46,XX gressive glomerulopathy, and a significant risk of gonadoblas- karyotype and normal female development. This indicates that toma. Mutations in the donor splice site in intron 9 of the the proper WT1 isoform ratio is critical for renal and testicular Wilms’ tumor (WT1) gene have been shown to cause Frasier development, but apparently does not affect either ovarian syndrome and are distinct from WT1 exon mutations associ- development or function. It is proposed that the clinical defi- ated with Denys-Drash syndrome. The WT1 gene, which is nition of Frasier syndrome should be broadened to include essential for normal kidney and gonadal development, encodes 46,XX females with normal genital development and focal a zinc finger transcription factor. The intron 9 alternative splice segmental glomerulosclerosis associated with a WT1 intron 9 donor site mutation seen in Frasier syndrome leads to loss of donor splice site mutation. Nephrologists need to consider the three amino acids (1KTS isoform), thus disrupting the normal possibility of this heritable syndrome in evaluation of females ratio of the 1KTS/2KTS isoforms critical for proper gonadal with focal segmental glomerulosclerosis and to consider their and renal development.
    [Show full text]
  • WAGR Syndrome
    International J. of Healthcare and Biomedical Research, Volume: 2, Issue: 4, July 2014, Pages 131-134 Case Report: WAGR Syndrome 1Dr.Prathamesh Patil , 2Dr. C Ashok kumar, 3Dr. Shashank Panwar , 4Dr. R Somdeepak Reddy , 5Dr. Pratik Gogri 1Junior Resident, Pediatrics, Pravara Institute of Medical sciences, Loni, Maharashtra, India 2 Associate Professor of Pediatrics, Pravara Institute of Medical sciences, Loni, Maharashtra, India 3 Junior Resident, Pediatrics, Pravara Institute of Medical sciences, Loni, Maharashtra, India 4 Junior Resident, Pediatrics, Pravara Institute of Medical sciences, Loni, Maharashtra, India 5 Junior Resident, Opthalmology, Pravara Institute of Medical sciences, Loni, Maharashtra, India Corresponding author: Dr. Prathamesh Patil; Email: [email protected] Abstract: WAGR Syndrome is a multiple congenital anomaly syndrome characterized by interstitial deletion of distal portion of chromosome 11p13. It is a gene deletion syndrome. WAGR is an acronym for W- Wilms tumor, A- aniridia, G- genital anomalies and R- mental retardation. Wilms tumor and male genital anomalies are caused by deletion of the WT1 tumor suppressor gene, and aniridia is caused by deletion of PAX6 ocular developmental gene. Mental retardation is thought to be a due of deletion of multiple as yet unidentified genes in the region. The patient needs a multidisciplinary management regimen encompassing the services of an ophthalmologist, radiologist, a pediatrician and pediatric surgeon. Herewith we reported a patient of developmental delay with abdominal distension, child also had aniridia. The child was managed by multidisciplinary approach. Key words: WAGR Syndrome Background: she was found to have aniridia, Wilms tumor and WAGR Syndrome is a multiple congenital anomaly mental retardation. The findings that aniridia is syndrome characterized by interstitial deletion of associated with Wilms tumor made that the findings distal portion of chromosome 11p13.
    [Show full text]
  • Construction of a Natural Panel of 11P11.2 Deletions and Further Delineation of the Critical Region Involved in Potocki–Shaffer Syndrome
    European Journal of Human Genetics (2005) 13, 528–540 & 2005 Nature Publishing Group All rights reserved 1018-4813/05 $30.00 www.nature.com/ejhg ARTICLE Construction of a natural panel of 11p11.2 deletions and further delineation of the critical region involved in Potocki–Shaffer syndrome Keiko Wakui1,12, Giuliana Gregato2,3,12, Blake C Ballif2, Caron D Glotzbach2,4, Kristen A Bailey2,4, Pao-Lin Kuo5, Whui-Chen Sue6, Leslie J Sheffield7, Mira Irons8, Enrique G Gomez9, Jacqueline T Hecht10, Lorraine Potocki1,11 and Lisa G Shaffer*,2,4 1Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA; 2Health Research and Education Center, Washington State University, Spokane, WA, USA; 3Dip. Patologia Umana ed Ereditaria, Sez. Biologia Generale e Genetica Medica, Universita` degli Studi di Pavia, Italy; 4Sacred Heart Medical Center, Spokane, WA, USA; 5Department of Obstetrics and Gynecology, National Cheng-Kung University Medical College, Taiwan; 6Department of Pediatrics, Taipei Municipal Women and Children’s Hospital, Taiwan; 7Genetic Health Services Victoria, Murdoch Children’s Research Institute, Department of Paediatrics, University of Melbourne, Victoria, Australia; 8Division of Genetics, Department of Medicine, Children’s Hospital, Harvard Medical School, Boston, MA, USA; 9Area de Gene´tica, Centro de Desarrollo Infantil y Departamento de Pediatrı´a Hospital Materno Infantil-Hospital Regional Universitario ‘Infanta Cristina’, Badajoz, Spain; 10Department of Pediatrics, University of Texas Medical School at Houston, TX, USA; 11Texas Children’s Hospital, Houston, TX, USA Potocki–Shaffer syndrome (PSS) is a contiguous gene deletion syndrome that results from haploinsufficiency of at least two genes within the short arm of chromosome 11[del(11)(p11.2p12)].
    [Show full text]
  • Wagr Syndrome Information
    CHROMOSOME DISORDER OUTREACH WAGR SYNDROME INFORMATION WAGR Syndrome WAGR is an acronym from the first letters of the mainmanifestations of this condition: Wilms tumor (W), aniridia (A), genital abnormalities (G) and retardation (R). The association of these defects has been known since the 1960s, but the chromosomal etiology of this syndrome was first reported in 1978-1979 (1). The chromosomal segment 11p13 includes two nearby genes – PAX6 and WT1, and the deletion of these genes determines the main manifestations of the syndrome. WAGR is a relatively common condition; at least 200 patients have been reported so far. The first manifestation of the syndrome is aniridia (absence of the iris). This defect may be revealed upon the examination of a newborn baby. Aniridia may be complete or partial. Glaucoma and cataracts often develop as a consequence of aniridia. Aniridia itself is caused by a mutation in the PAX6 gene and in many families this defect is inherited in an autosomal dominant manner. If however aniridia in a newborn baby is sporadic it is a strong indication for a cytogenetic examination to exclude deletion 11p13 underlying this eye defect. At least one third of patients with sporadic aniridia may have 11p13 deletion and (as a result) other manifestations of WAGR syndrome. Molecular cytogenetic examinations show that in rare instances aniridia may be caused by deletions of the regulatory elements nearby the PAX6 gene, but the gene itself may be unaffected (2). Genital abnormalities vary from one patient to another. Most boys reveal cryptorchidism. Hypospadias or ambiguous genitalia are relatively uncommon. Girls usually do not reveal genital abnormalities, although there are reports of streaked ovaries, hypoplastic or bicornuate (a type of congenital uterine malformation or müllerian duct anomalies in which the uterus page 1 appears to be heart shaped) uterus, etc.
    [Show full text]
  • WT1 Gene Wilms Tumor 1
    WT1 gene Wilms tumor 1 Normal Function The WT1 gene provides instructions for making a protein that is necessary for the development of the kidneys and gonads (ovaries in females and testes in males) before birth. After birth, WT1 protein activity is limited to a structure known as the glomerulus, which filters blood through the kidneys. The WT1 protein plays a role in cell growth, the process by which cells mature to perform specific functions (differentiation), and the self- destruction of cells (apoptosis). To carry out these functions, the WT1 protein regulates the activity of other genes by attaching (binding) to specific regions of DNA. On the basis of this action, the WT1 protein is called a transcription factor. Health Conditions Related to Genetic Changes Denys-Drash syndrome At least 80 mutations in the WT1 gene have been found to cause Denys-Drash syndrome, a condition that affects development of the kidneys and genitalia and most often affects males. These mutations are germline, which means they are present in cells throughout the body. The mutations that cause Denys-Drash syndrome almost always occur in areas of the gene known as exon 8 and exon 9. Most of these mutations result in changes in single protein building blocks (amino acids) in the WT1 protein. The most common mutation that causes Denys-Drash syndrome (found in about 40 percent of cases) replaces the amino acid arginine with the amino acid tryptophan at protein position 394 (written Arg394Trp or R394W). The mutations that cause Denys-Drash syndrome lead to the production of an abnormal WT1 protein that cannot bind to DNA.
    [Show full text]
  • WINGS Spring Summer 2009
    WINGS WAGR Information, News, Gorilla Stories International WAGR Syndrome Association www.wagr.org P.O. Box 392 Allen Park, MI 48101 Spring/Summer 2009 We continue to pursue grants as well Calling all UK WAGR as creative ways to raise funds for the Families From the organization. The IWSA “End of the Year Ask” letter was very successful The Aniridia Network UK will hold- President's and we plan to continue this every ing their annual gathering in May. year. Jenny Langley, ANUK Secretary and pen WAGR representative would like to Unfortunately the March of Dimes know if there are any WAGR families Michigan Chapter Community award interested in gettting together? Dear Families & Friends, was not renewed for 2009 due to cut backs. This $1,000 grant was used Meeting space would need to be I would like to begin by thanking all in 2008 to offset some of the secured. If you are interested in a UK WAGR Gathering please contact our donors. During these difficult and printing/mailing expense of our news- Jenny at [email protected] uncertain times your kindness and letter. generosity is helping offset many Details of the Aniridia Network UK organization expenses. Just a reminder that our online survey 2009 AGM: "WAGR Syndrome: The Kidney and Date: 16th May 2009 This includes the printing of our Urinary Tract" is currently underway. Time: 10:30am - 4:30pm and op- updated brochures, printing and For more information please visit our tional social event afterwards mailing expense of our newsletters, website at Venue: The Resource Centre, gifts to hospitalized children, general http://www.wagr.org/survey2008.ht- Holloway Road, London operating expenses, rental space and ml.
    [Show full text]
  • What Is WAGR Syndrome
    wagr.org http://wagr.org/?page_id=3492 What is WAGR Syndrome What is WAGR syndrome? Below is an overview of WAGR syndrome. Please use the sidebars at right to access additional information about the conditions associated with this disorder. WAGR syndrome is a rare genetic condition that can affect both boys and girls. Babies born with WAGR syndrome often have eye problems, and are at high risk for developing certain types of cancer, and a range of developmental delays. The term “WAGR” stands for the first letters of the physical and mental problems associated with the condition: (W)ilms’ Tumor, the most common form of kidney cancer in children. (A)niridia, some or complete absence of the colored part of the eye, called the iris (singular), or irises/irides (plural). (G)enitourinary problems, such as testicles that are not descended or hypospadias (abnormal location of the opening for urination) in boys, or genital or urinary problems inside the body in girls. (R)ange of developmental delays. Most people who have WAGR syndrome have two or more of these conditions. Also, people can have WAGR syndrome, but not have all of the above conditions. Other names for WAGR syndrome that are used are: WAGR Complex Wilms’ Tumor-Aniridia-Genitourinary Anomalies-Mental Retardation Syndrome Wilms’ Tumor-Aniridia-Gonadoblastoma-Mental Retardation Syndrome Chromosome 11p deletion syndrome 11p deletion syndrome The cause of WAGR syndrome is deletion of a group of genes located on chromosome number 11 (11p13 – the “p13″ refers to the specific place on chromosome 11 that is affected). Chromosomes are packages of genetic characteristics.
    [Show full text]
  • Bilateral Wilms Tumour: a Review of Clinical and Molecular Features
    Expert Reviews in Molecular Medicine, Vol. 19; e8; 1 of 13. REVIEW © Cambridge University Press, 2017. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. doi:10.1017/erm.2017.8 Bilateral Wilms tumour: a review of clinical and molecular features JOCELYN CHARLTON1†, SABINE IRTAN1,2†, CHRISTOPHE BERGERON3, KATHY PRITCHARD-JONES1* 1UCL Institute of Child Health, University College London, London, UK, 2Paediatric Surgery Department, Trousseau Hospital, Paris, France, and 3Centre Léon Bérard, Institut d’Hématologie et d’Oncologie Pédiatrie, Lyon, France Wilms tumour (WT) is the most common paediatric kidney cancer and affects approximately one in 10 000 children. The tumour is associated with undifferentiated embryonic lesions called nephrogenic rests (NRs) or, when diffuse, nephroblastomatosis. WT or NRs can occur in both kidneys, termed bilateral disease, found in only 5–8% of cases. Management of bilateral WT presents a major clinical challenge in terms of maximising survival, preserving renal function and understanding underlying genetic risk. In this review, we compile clinical data from 545 published cases of bilateral WT and discuss recent progress in understanding the molecular basis of bilateral WT and its associated precursor NRs in the context of the latest radiological, surgical and epidemiological features. Introduction embryonic renal cells persisting in a mature kidney Wilms tumour (WT) is a rare kidney cancer that occurs that result from incomplete differentiation of metaneph- almost exclusively in childhood, with a prevalence of ric blastema into mature renal parenchyma (Refs 6, 7).
    [Show full text]
  • Glaucoma and Frequency of Ocular and General Diseases in 30 Patients with Aniridia: a Clinical Study
    Eur J Ophthalmol22 (2012; :1) 104-110 DOI: 10.5301/EJO.2011.8318 ORIGINAL ARTICLE Glaucoma and frequency of ocular and general diseases in 30 patients with aniridia: a clinical study Eugen Gramer1*, Constantin Reiter1*, Gwendolyn Gramer2 1Department of Ophthalmology, University Würzburg, Würzburg - Germany 2University Hospital for Pediatric and Adolescent Medicine, University Heidelberg, Heidelberg - Germany Department of Ophthalmology, University Würzburg, Würzburg - Germany PURPOSE. To evaluate the following in patients with aniridia: age at first examination at the University Eye Hospital and age at diagnosis of glaucoma; visual acuity; frequency of family history of aniridia; and frequency of ocular and general diseases associated with aniridia. METHODS. This was a consecutive examination of 30 unrelated patients with aniridia and retrospective evaluation of ophthalmologic, pediatric, and internal findings. The relative frequency of age at glauco- ma diagnosis within decades was evaluated for the 20 patients with aniridia and glaucoma. Statistical analysis was performed using the Mann-Whitney test. RESULTS. Relative frequency of the age of patients with aniridia at time of glaucoma diagnosis within the following decades was as follows: from birth to 9 years: 15%, 10-19: 15%, 20-29: 15%, 30-39: 15%, 40-49: 35%, and 50-59: 5%. Visual acuity in the better eye of 20/100 or less was found in 60%. Family history of aniridia was found in 33.3% of patients, with 1-4 relatives with aniridia. A total of 76.7% of patients had congenital cataract, and 66.7% had glaucoma. Mean maximum intraocular pressure of the 20 patients with glaucoma was 35.9 mmHg in the right and 32.6 mmHg in the left eye.
    [Show full text]
  • Insights from the 3Rd Pan-European Conference on Congenital Aniridia
    Insights from the 3rd Pan-European Conference on Congenital Aniridia and WAGR Syndrome Duisburg, Germany 26-29 August, 2016 Kelly Trout, BSN, RN Health Consultant International WAGR Syndrome Association http://www.wagr.org In Greek mythology, “Iris” was a goddess, the personification of the rainbow The purpose of this paper is to describe recent medical research and clinical consensus presented at the third Pan-European Conference on Congenital Aniridia and WAGR syndrome. It is hoped that this paper will be of assistance to patients, parents, and local clinicians, but it is not intended to provide medical advice. Topics: Ocular Surface Disease (OSD) and Aniridia-Associated Keratopathy (AAK) Genetics of Aniridia Artificial Iris Glaucoma Cataract Aniridia Syndrome Early Vision Development/Low Vison Care The Role of the BDNF gene Sleep Disturbances in Aniridia Aniridia in WAGR syndrome WAGR syndrome: clinical guidelines and Wilms tumor Ocular Surface Disease (OSD)/Aniridia-Associated Keratopathy (AAK) Ocular Surface Disease (OSD)/AAK occurs at some point in more than 90% of patients with aniridia o Often begins in first decade of life o Often worsens after ocular surgery or treatment for glaucoma o Caused by limbal (stem cell) deficiency o Extreme care should be taken to preserve the cornea in patients with congenital aniridia . minimize number and extent of oculosurgical procedures whenever possible . minimize ptosis surgery (to decrease dry eye) . recognize ocular infections (“pinkeye”) promptly, treat with gentle antibiotics
    [Show full text]
  • Wilms Tumor - Aniridia Syndrome (WAGR Syndrome) - Implication for the Importance of Genetic Diagnosis and Prospective Tumor Screening
    Wilms Tumor - Aniridia Syndrome (WAGR Syndrome) - Implication for the Importance of Genetic Diagnosis and Prospective Tumor Screening - 1Akira Kikuchi MD, 2Hirofumi Ohashi MD, 1,5Daisuke Tomizawa MD, 3,6Tadashi Iwanaka MD, 4Eiji Oguma MD and 1Ryoji Hanada MD. 1Division of Hematology / Oncology, Saitama Children's Medical Center, 2Division of Medical Genetics, Saitama Children's Medical Center, 3Department of Surgery, Saitama Children's Medical Center, 4Department of Radiology, Saitama Children's Medical Center, 5Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan. 6Department of Pediatric Surgery, University of Tokyo, Tokyo, Japan. ABSTRACT Association between Wilms tumor and aniridia is well recognized as WAGR syndrome.1, 2 The responsible genes The association between Wilms tumor and aniridia is well for Wilms tumor (WT1)3, 4 and aniridia (PAX6)5 are located recognized. We performed FISH analysis of WT1 and PAX6 closely at p13 on the short arm of chromosome 11 within 1 genes in aniridia patients and prospective tumor screening in Mb distance and large interstitial deletion of 11p causes patients with WT1 germ line deletion. A two-month old girl Wilms tumor and aniridia simultaneously in affected with aniridia showing WT1 deletion underwent prospective patients. Generally, aniridia patients are at high risk for the abdominal ultrasonic echograms at two-month intervals and development of Wilms tumor. However, we previously bilateral renal tumors were detected four months later. She reported that the risk for Wilms tumor in aniridia patients remains well after chemotherapy and delayed primary surgery can be predicted by FISH analysis of WT1 gene and PAX6 at 48 months.
    [Show full text]