Achados renais e urinários em 20 pacientes com síndrome de Williams-Beuren diagnosticados pelo teste de hibridização in situ por fluoresceína (FISH)

PURPOSE: Williams-Beuren syndrome is a rare multiple anomalies/mental retardation syndrome caused by deletion of contiguous genes at chromosome region 7q11.23. The aim of this work was to determine the frequency and the types of renal and urinary tract anomalies in 20 patients with Williams-Beuren syndrome. METHODS: The fluorescence in situ hybridization test using a LSI Williams syndrome region DNA probe was performed for all 20 patients to confirm the diagnosis of Williams-Beuren syndrome. A prospective study was performed in order to investigate renal and urinary aspects using laboratory assays to check renal function, ultrasonography of the kidneys and urinary tract, voiding cystourethrogram and urodynamics. RESULTS: Deletion of the elastin gene (positive fluorescence in situ hybridization test) was found in 17 out of 20 patients. Renal alterations were diagnosed in 5 of 17 (29%) the patients with the deletion and in 1 of 3 patients without the deletion. Fourteen patients with the deletion presented dysfunctional voiding. Arterial hypertension was diagnosed in 3 patients with deletions and 1 of these presented bilateral stenosis of the renal arteries. CONCLUSIONS: Due to the high incidence of renal and urinary abnormalities in Williams-Beuren syndrome, performing a systematic laboratory and sonographic evaluation of the patients is recommended.OBJETIVO: A síndrome de Williams-Beuren é uma rara síndrome de deleção de genes contíguos que cursa com múltiplas anomalias congênitas, deficiência mental e anomalias renais e urinárias. O objetivo deste trabalho foi determinar a freqüência e os tipos de anomalias renais e urinárias em 20 pacientes com síndrome de Williams-Beuren diagnosticados pelo teste de hibridização in situ por fluorescência. MÉTODOS: Estudou-se prospectivamente os aspectos renais e urinários através de avaliação laboratorial da função renal, ultrassonografia de rins e vias urinárias, uretrocistografia miccional e estudo urodinâmico. O teste da hibridização in situ por fluorescência com a sonda LSI Williams Region foi feito nos 20 pacientes com síndrome de Williams-Beuren para a confirmação do diagnóstico. RESULTADOS E DISCUSSÃO: A deleção do gene da elastina (teste de hibridização in situ por fluorescência positivo) foi detectado em 17/20 afetados (85%). As alterações renais foram diagnosticadas em 5/17 (29%) dos pacientes com a deleção e em 1/3 dos indivíduos sem a deleção. Catorze pacientes com a deleção apresentavam disfunções miccionais. A hipertensão arterial foi diagnosticada em três pacientes com a deleção e um deles apresentava estenose bilateral das artérias renais. CONCLUSÕES: Devido à elevada incidência de anormalidades renais e do trato urinário na síndrome de Williams-Beuren, recomenda-se realizar uma avaliação laboratorial e de imagem sistematizada nos pacientes

Noonan syndrome: a clinical and genetic study of 31 patients

Noonan syndrome is a multiple congenital anomaly syndrome, inherited in an autosomal dominant pattern. We studied 31 patients (18 males and 13 females) affected by this disorder regarding their clinical and genetic characteristics. The most frequent clinical findings were short stature (71%); craniofacial dysmorphisms, especially hypertelorism, ptosis, downslanting of the palpebral fissures; short or webbed neck (87%); cardiac anomalies (65%), and fetal pads in fingers and toes (70%). After studying the probands' first-degree relatives, we made the diagnosis of Noonan syndrome in more than one family member in three families. Therefore, the majority of our cases were sporadic.A síndrome de Noonan é uma patologia de múltiplas anomalias congênitas, herdada em um padrão de herança autossômico dominante. Estudamos 31 pacientes (18 do sexo masculino e 13 do sexo feminino) afetados por essa síndrome quanto aos aspectos clínicos e genéticos. As características clínicas mais freqüentemente observadas foram a baixa estatura (71%); os dismorfismos craniofaciais, principalmente o hipertelorismo, a ptose e a inclinação ínfero-lateral das fendas palpebrais; o pescoço curto ou alado (87%); as anomalias cardíacas (65%) e a presença de coxins nas pontas dos dedos das mãos e pés (70%). Após estudarmos os parentes de primeiro grau dos probandos, fizemos o diagnóstico da Síndrome de Noonan em um deles em três famílias. Portanto, a maioria dos nossos casos foram esporádicos

Síndrome de Williams: proposta de sistema de pontuação para diagnóstico clínico

OBJECTIVE: To develop a scoring system based on clinical findings to assist pediatricians in the diagnosis of William syndrome and to delineate when the fluorescent in-situ hybridization test to detect the microdeletion at 7q11.23 may be needed. METHODS: The fluorescent in-situ hybridization test was performed on 20 patients presenting William syndrome suggestive clinical features. Eleven studies were selected from the literature in which there were 2 groups: patients with positive or negative fluorescent in-situ hybridization tests. Forty-two clinical characteristics were compared to those reported in the literature to determine which ones were associated with the affected patients (ie, bearing deletions) using meta-analysis. The 2-tailed Fisher exact test were used so that the frequency of findings observed in fluorescent in-situ hybridization positive and fluorescent in-situ hybridization negative patients could be compared in the present study together with the patients from the literature. We developed a scoring system based on clinical findings and their significant associations with patients with positive fluorescent in-situ hybridization tests. From themean and standard-deviation values of the data from our patients, we determined the cut-off score that that indicated the need for a fluorescent in-situ hybridization test to confirm diagnosis. RESULTS: Seventeen patients were fluorescent in-situ hybridization positive, and 3 were fluorescent in-situ hybridization negative. The more discriminative findings among fluorescent in-situ hybridization positive patients were the following: typical facies, low birth weight, feeding difficulties, constipation, supravalvar aortic stenosis, mental retardation, and friendly personality. The distribution of the points among the 20 patients ranged from 19 to 28 points with a mean value of 23.3 out of a possible total of 31 points. The cut-off score that indicated the need for a fluorescent in-situ hybridization test was 20. CONCLUSIONS: Our scoring system enables physicians to differentiate between those individuals who can be reliably diagnosed as having Williams syndrome solely from the clinical findings and those who need to undergo fluorescent in-situ hybridization testing for a correct diagnosis.OBJETIVOS: Desenvolver um sistema de pontuação (Score) baseado nos achados clínicos para auxiliar os pediatras no diagnóstico clínico da Síndrome de Williams-Beuren e na indicação do teste de hibridização in situ por fluorescência para detectar a microdeleção em 7q11.23. MÉTODOS: O teste de hibridização in situ por fluorescência foi feito em 20 acometidos pela Síndrome de Williams-Beuren, nos quais 42 achados clínicos foram estudados. Para estabelecer quais desses achados estariam associados ao teste de hibridização in situ por fluorescência positivo, realizou-se uma metanálise com 11 trabalhos da literatura em que havia dois grupos, hibridização in situ por fluorescência positivo e negativo. As freqüências dos achados presentes nos indivíduos fluorescência positivo e fluorescência negativo neste estudo foram comparadas em conjunto com os pacientes da literatura através do teste exato de Fisher. Elaboramos um sistema de pontuação (score) baseado nos achados que mostraram correlação significante (

DiGeorge Syndrome: a not so rare disease

INTRODUCTION: The DiGeorge Syndrome was first described in 1968 as a primary immunodeficiency resulting from the abnormal development of the third and fourth pharyngeal pouches during embryonic life. It is characterized by hypocalcemia due to hypoparathyroidism, heart defects, and thymic hypoplasia or aplasia. Its incidence is 1:3000 live births and, despite its high frequency, little is known about its natural history and progression. ←This is probably due to diagnostic difficulties and the great variety of names used to describe it, such as velocardiofacial, Shprintzen, DiGeorge, and CATCH 22 Syndromes, as well as conotruncal facial anomaly. All represent the same genetic condition, chromosome 22q11.2 deletion, which might have several clinical expressions. OBJECTIVES: To describe clinical and laboratorial data and phenotypic characteristics of patients with DiGeorge Syndrome. METHODS: Patients underwent standard clinical and epidemiological protocol and tests to detect heart diseases, facial abnormalities, dimorphisms, neurological or behavioral disorders, recurrent infections and other comorbidities. RESULTS: Of 14 patients (8m - 18y11m), only one did not have 22q11.2 deletion detected. The main findings were: conotruncal malformation (n = 12), facial abnormalities (n = 11), hypocalcemia (n = 5) and low lymphocyte count (n=2). CONCLUSION: The authors pointed out the necessity of DGS suspicion in all patient presenting with heart defects, facial abnormalities (associated or not with hypocalcemia), and immunological disorders because although frequency of DGS is high, few patients with a confirmed diagnosis are followed up

Increase of Ceftazidime- and Fluoroquinolone-Resistant Klebsiella pneumoniae and Imipenem-Resistant Acinetobacter spp. in Korea: Analysis of KONSAR Study Data from 2005 and 2007

PURPOSE: Antimicrobial resistance monitoring could be a useful source of information for treating and controlling nosocomial infections. We analyzed antimicrobial resistance data generated by Korean Hospitals and by a commercial laboratory in 2005 and 2007. MATERIALS AND METHODS: Susceptibility data for 2005 and 2007 were collected from 37 and 41 hospitals, respectively, and from one commercial laboratory. Intermediate susceptibility was not included in the calculation of resistance rates. RESULTS: Methicillin-resistant Staphylococcus aureus (MRSA) (64%), third-generation cephalosporin-resistant Klebsiella pneumoniae (29%), fluoroquinolone-resistant Escherichia coli (27%), Pseudomonas aeruginosa (33%), and Acinetobacter spp. (48%), and amikacin-resistant P. aeruginosa (19%) and Acinetobacter spp. (37%) were prevalent in hospitals in 2007. A gradual increase of vancomycin-resistant Enterococcus faecium and imipenem-resistant Acinetobacter spp. was observed. Higher incidences of thirdgeneration cephalosporin-resistant E. coli and K. pneumoniae and imipenemresistant P. aeruginosa were found in the commercial laboratory than in the hospitals. CONCLUSION: Methicillin-resistant S. aureus, third-generation cephalosporin- resistant K. pneumoniae, and fluoroquinolone-resistant E. coli, P. aeruginosa and Acinetobacter spp. remain prevalent in Korea, while the incidence of vancomycin-resistant E. faecium and imipenem-resistant Acinetobacter spp. has increased gradually. The higher prevalences of third-generation cephalosporinresistant E. coli and K. pneumoniae, and imipenem-resistant P. aeruginosa in the commercial laboratory are a new concern.ope

Detection of deletions at 7q11.23 in Williams-Beuren syndrome by polymorphic markers

INTRODUCTION: Williams-Beuren syndrome (WBS; OMIM 194050) is caused by a hemizygous contiguous gene microdeletion at 7q11.23. Supravalvular aortic stenosis, mental retardation, overfriendliness, and ocular and renal abnormalities comprise typical symptoms in WBS. Although fluorescence in situ hybridization is widely used for diagnostic confirmation, microsatellite DNA markers are considered highly informative and easily manageable. OBJECTIVES: This study aimed to test the microsatellite markers for the diagnosis of Williams-Beuren syndrome, to determine the size and parental origin of microdeletion, compare the clinical characteristics between patients with different sizes of the deletion and parental origin. METHODS: We studied 97 patients with clinical diagnosis of Williams-Beuren syndrome using five microsatellite markers: D7S1870, D7S489, D7S613, D7S2476 and D7S489_A. RESULTS AND DISCUSSION: Using five markers together, the result was informative in all patients. The most informative marker was D7S1870 (78.4%), followed by D7S613 (75.3%), D7S489 (70.1%) and D7S2476 (62.9%). The microdeletion was present in 84 (86.6%) patients and absent in 13 (13.4%) patients. Maternal deletions were found in 52.4% of patients and paternal deletions in 47.6% of patients. The observed size of deletions was 1.55 Mb in 76/ 84 patients (90.5%) and 1.84 Mb in 8/84 patients (9.5%). SVAS as well as ocular and urinary abnormalities were more frequent in the patients with a deletion. There were no clinical differences in relation to either the size or parental origin of the deletion. CONCLUSION: Using these five selected microsatellite markers was informative in all patients, thus can be considered an alternative method for molecular diagnosis in Williams-Beuren syndrome

Nephrogenic Diabetes Insipidus (NDI): Clinical, Laboratory and Genetic Characterization of Five Brazilian Patients

INTRODUCTION: Nephrogenic diabetes insipidus is characterized by a lack of response in the distal nephron to the antidiuretic hormone arginine vasopressin. Manifestations include polyuria, polydipsia, hyposthenuria, recurrent episodes of dehydration and fever and growth failure. Most cases are caused by mutations in the AVPR2 gene. The mutant receptors are trapped intracellularly. METHOD: We studied five boys using clinical, laboratory and molecular data. The mean age at diagnosis was 14.6 months (range 6 to 24) and 12.2 years (7.8 to 19) after the follow-up period. The mean period of follow-up was 132.2 ± 50.9 months. RESULTS: The geometric means of the z-scores of weight and stature were -4.5 and -3.6, respectively, at diagnosis. At the last medical appointment, the z-scores of weight and stature were -0.3 and -0.9, respectively. Three patients were diagnosed with ureterohydronephrosis and exhibited increased post-void urine volume. Mutations in the AVPR2 gene were found in all patients, and the carrier status was confirmed in four of five cases. Two unrelated children presented identical mutations (S167L) in arginine vasopressin R2. Two of the patients had a mutation that has already been described in other Brazilian families (R337X), and one patient showed a de novo mutation (Y128D) in arginine vasopressin R2, since his mother's molecular analysis was normal. The recurrence risk for this family was significantly reduced. CONCLUSION: This study reports the clinical and laboratory characterization of Nephrogenic diabetes insipidus and reiterates the importance of the genetic basis that underlies the disease diagnosis and genetic counseling