Visual loss as first clinical manifestation of X-linked adrenoleukodystrophy / Perda visual como primeira manifestação clínica de adrenoleucodistrofia ligada ao X

Abstract X-linked adrenoleukodystrophy (X-ALD) represents a group of diseases characterized by the accumulation of very long chain fattyacids (VLCFAs) in the tissues. Its clinical manifestations are usually manifold. Visual changes may be present, but they often appear later in the disease. We describe here the case of a 9-year-old boy with X-ALD, whose first symptom was visual loss, which began at 8 years of age. His ophthalmologic evaluation revealed no alterations. Shortly thereafter, he suffered a head injury. The magnetic resonance imaging of brain revealed findings that led to the suspicion of X-ALD. The plasma VLCFA dosage confirmed this diagnosis. This report aims toshow that in cases of visual loss with a normal ophthalmic examination, a high index of suspicion should be given for conditions suchas X-ALD, since it affects the cortical routes related to vision. Fundoscopy findings appear late in X-ALD.

Resumo A adrenoleucodistrofia ligada ao X (X-ALD) representa um grupo de doenças caracterizadas pelo acúmulo de ácidos graxos de cadeia muito longa (VLCFAs) nos tecidos. Suas manifestações clínicas costumam ser múltiplas. Alterações visuais podem estar presentes, contudo costumam surgir mais tardiamente na doença. Descrevemos aqui o caso de um menino de 9 anos com X-ALD, cujo primeiro sintoma foi perda visual, iniciada aos 8 anos de idade. A sua avaliação oftalmológica não revelou alterações. Pouco tempo depois, ele sofreu um traumatismo craniano. A imagem de ressonância magnética de encéfalo revelou achados que levaram a suspeita de X-ALD. A dosagem dos VLCFAs no plasma confirmou este diagnóstico. Este relato tem como objetivo mostrar que em casos de perda visual com um exame oftalmológico normal, deve-se ter um alto índice de suspeita para condições como a X-ALD, pois a mesma afeta as vias corticais relacionadas à visão. Nessa doença, os achados da fundoscopia aparecem mais tardiamente.

SIBLINGS AFFECTED BY ECTRODACTYLY-ECTODERMAL DYSPLASIA AND CLEFT LIP/PALATE (EEC) SYNDROME PRESENTING NORMAL PARENTS: GERMLINE MOSAICISM? / IRMÃOS AFETADOS PELA SÍNDROME DE ECTRODACTILIA, DISPLASIA ECTODÉRMICA E FISSURA LABIOPALATAL (EEC) COM PAIS HÍGIDOS: MOSAICISMO GERMINATIVO?

OBJECTIVE: EEC is an acronym for an autosomal dominant syndrome clinically characterized by ectrodactyly (E), ectodermal dysplasia (E) and cleft lip/palate (C). Our aim was to describe a rare case of siblings affected by ectrodactyly, ectodermal dysplasia and cleft lip/palate (EEC) syndrome presenting normal parents. CASE DESCRIPTION: The patient was the third son of young and healthy parents. The parents did not present any minor or major anomaly of hands, feet or skin, hair and teeth. The couple had a previous history of two children with hands and feet malformations similar to the present patient. The first was a stillborn, and the second one a preterm infant that died in the first days after birth due to the consequences of prematurity. After birth, the patient presented respiratory distress with need of endotracheal intubation and mechanic ventilation. At physical examination, there were cleft lip/palate, hands and feet ectrodactyly, with absence of the second and third fingers in both hands, and reduction defects affecting mainly the second toes. The child presented pneumothorax and cardiorespiratory arrest and died at 1 month and 26 days. COMMENTS: Herein we described a case of siblings with EEC syndrome, indicative of a germline mosaicism. In the literature review, there was the description of only three similar reports. The present case strengthens the possibility that germline mosaicism may be a more common inheritance mechanism than previously thought in cases of EEC syndrome.

OBJETIVO: EEC é um acrônimo para uma síndrome autossômica dominante caracterizada clinicamente por ectrodactilia (E), displasia ectodérmica efissura labiopalatal (C). Nosso objetivo foi relatar um caso raro de irmãos afetados pela síndrome de ectrodactilia, displasia ectodérmica efissura labiopalatal (EEC) com pais hígidos. DESCRIÇÃO DO CASO: O paciente era o terceiro filho de pais jovens e hígidos, os quais não apresentavam nenhuma anomalia menor ou maior de mãos e pés ou anomalias de pele, cabelos e dentes. O casal tinha história prévia de duas crianças com malformação de mãos e pés, similar à do paciente. O primeiro foi natimorto e o segundo, prematuro, falecendo nos primeiros dias de vida, pelas consequências da prematuridade. Após o nascimento, o paciente apresentou desconforto respiratório, com necessidade de intubação orotraqueal e ventilação mecânica. No exame físico, verificaram-se a presença de fissura labiopalatal e ectrodactilia de mãos e pés, com ausência do segundo e terceiro dedos em ambas as mãos e defeitos de redução acometendo principalmente o segundo dedo dos pés. A criança apresentou pneumotórax e parada cardiorrespiratória, morrendo com 1 mês e 26 dias de vida. COMENTÁRIOS: Descrevemos aqui um caso de irmãos com síndrome EEC, indicativo de mosaicismo germinativo. Na revisão da literatura, observaram-se apenas três relatos similares. Este caso reforça a possibilidade do mosaicismo germinativo ser um mecanismo de herança mais comum do que se acreditava previamente para casos da síndrome EEC.

Irmãos afetados pela síndrome de ectrodactilia, displasia ectodérmica e fissura labiopalatal (eec) com pais hígidos: mosaicismo germinativo? / Siblings affected by ectrodactyly-ectodermal dysplasia and cleft lip/palate (eec) syndrome presenting normal parents: germline mosaicism?

RESUMO Objetivo: EEC é um acrônimo para uma síndrome autossômica dominante caracterizada clinicamente por ectrodactilia (E), displasia ectodérmica efissura labiopalatal (C). Nosso objetivo foi relatar um caso raro de irmãos afetados pela síndrome de ectrodactilia, displasia ectodérmica efissura labiopalatal (EEC) com pais hígidos. Descrição do caso: O paciente era o terceiro filho de pais jovens e hígidos, os quais não apresentavam nenhuma anomalia menor ou maior de mãos e pés ou anomalias de pele, cabelos e dentes. O casal tinha história prévia de duas crianças com malformação de mãos e pés, similar à do paciente. O primeiro foi natimorto e o segundo, prematuro, falecendo nos primeiros dias de vida, pelas consequências da prematuridade. Após o nascimento, o paciente apresentou desconforto respiratório, com necessidade de intubação orotraqueal e ventilação mecânica. No exame físico, verificaram-se a presença de fissura labiopalatal e ectrodactilia de mãos e pés, com ausência do segundo e terceiro dedos em ambas as mãos e defeitos de redução acometendo principalmente o segundo dedo dos pés. A criança apresentou pneumotórax e parada cardiorrespiratória, morrendo com 1 mês e 26 dias de vida. Comentários: Descrevemos aqui um caso de irmãos com síndrome EEC, indicativo de mosaicismo germinativo. Na revisão da literatura, observaram-se apenas três relatos similares. Este caso reforça a possibilidade do mosaicismo germinativo ser um mecanismo de herança mais comum do que se acreditava previamente para casos da síndrome EEC.

ABSTRACT Objective: EEC is an acronym for an autosomal dominant syndrome clinically characterized by ectrodactyly (E), ectodermal dysplasia (E) and cleft lip/palate (C). Our aim was to describe a rare case of siblings affected by ectrodactyly, ectodermal dysplasia and cleft lip/palate (EEC) syndrome presenting normal parents. Case description: The patient was the third son of young and healthy parents. The parents did not present any minor or major anomaly of hands, feet or skin, hair and teeth. The couple had a previous history of two children with hands and feet malformations similar to the present patient. The first was a stillborn, and the second one a preterm infant that died in the first days after birth due to the consequences of prematurity. After birth, the patient presented respiratory distress with need of endotracheal intubation and mechanic ventilation. At physical examination, there were cleft lip/palate, hands and feet ectrodactyly, with absence of the second and third fingers in both hands, and reduction defects affecting mainly the second toes. The child presented pneumothorax and cardiorespiratory arrest and died at 1 month and 26 days. Comments: Herein we described a case of siblings with EEC syndrome, indicative of a germline mosaicism. In the literature review, there was the description of only three similar reports. The present case strengthens the possibility that germline mosaicism may be a more common inheritance mechanism than previously thought in cases of EEC syndrome.

Birth weight, length and head circumference: Progression and impact over the outcome of patients with congenital heart disease.

BACKGROUND: There are few studies assessing the birth measures of patients with congenital heart disease (CHD). Our aim to evaluate their progression and impact over the outcome. METHODS: The cases consisted of patients with CHD during their first hospitalization in a reference cardiac and pediatric intensive care unit (ICU) from Southern Brazil. Controls were composed of patients with no clinical evidence of CHD hospitalized soon after cases. The cases underwent high-resolution karyotype and fluorescence in situ hybridization (FISH) for 22q11 microdeletion. We analyzed birth weight, length and head circumference of patients of both groups. For CHD patients, we evaluated their progression and impact until hospitalization at ICU. RESULTS: Our sample was composed of 198 cases and controls. We observe a difference in birth weight of CHD patients only in relation to general population. There was a significant increase in children with CHD and weight below the lower limit from birth until the hospitalization at ICU, and this occurred more in those without complex CHD. Syndromic patients and with an extracardiac malformation also presented a greater difficulty to maintain not only the weight but also the length/height until the hospitalization. Individuals with weight below the lower limit at hospitalization who died had a tendency to present longer stay at ICU. CONCLUSIONS: Some CHD patients, especially without complex defects, and with syndromic aspect and a major extracardiac malformation, present a higher difficult to maintain their weight and growth, and, therefore, may be at risk and should be more closely monitored.

Microcephaly-chorioretinopathy syndrome, autosomal recessive form. A case report / Síndrome de microcefalia-coriorretinopatia, forma autossômica recessiva. Um relato de caso

CONTEXT: The autosomal recessive form of microcephaly-chorioretinopathy syndrome is a rare genetic condition that is considered to be an important differential diagnosis with congenital toxoplasmosis.CASE REPORT: Our patient was a seven-year-old white boy who was initially diagnosed with congenital toxoplasmosis. However, his serological tests for congenital infections, including toxoplasmosis, were negative. He was the first child of young, healthy and consanguineous parents (fourth-degree relatives). The parents had normal head circumferences and intelligence. The patient presented microcephaly and specific abnormalities of the retina, with multiple diffuse oval areas of pigmentation and patches of chorioretinal atrophy associated with diffuse pigmentation of the fundus. Ophthalmological evaluations on the parents were normal. A computed tomography scan of the child's head showed slight dilation of lateral ventricles and basal cisterns without evidence of calcifications. We did not find any lymphedema in his hands and feet. He had postnatal growth retardation, severe mental retardation and cerebral palsy.CONCLUSIONS: The finding of chorioretinal lesions in a child with microcephaly should raise suspicions of the autosomal recessive form of microcephaly-chorioretinopathy syndrome, especially in cases with an atypical pattern of eye fundus and consanguinity. A specific diagnosis is essential for an appropriate clinical evaluation and for genetic counseling for the patients and their families.

CONTEXTO: A forma autossômica recessiva da síndrome de microcefalia-coriorretinopatia é condição genética rara, considerada um importante diagnóstico diferencial com toxoplasmose congênita.RELATO DO CASO: O paciente era um menino branco de sete anos de idade, inicialmente diagnosticado com toxoplasmose congênita. No entanto, suas sorologias para infecções congênitas, incluindo a toxoplasmose, eram negativas. Ele foi o primeiro filho de pais jovens, hígidos e consanguíneos (parentes de quarto grau). Os pais apresentavam perímetro cefálico e inteligência normais. O paciente apresentava microcefalia e anormalidades específicas da retina com áreas ovais de pigmentação múltiplas e difusas, além de manchas de atrofia coriorretiniana associadas à pigmentação difusa do fundo de olho. A avaliação oftalmológica dos pais foi normal. A tomografia computadorizada de crânio da criança mostrou discreta dilatação dos ventrículos laterais e cisternas basais, sem evidência de calcificações. Nós não verificamos a presença de linfedema em suas mãos e pés. Ele possuía retardo do crescimento pós-natal, deficiência mental grave e paralisia cerebral.CONCLUSÃO: O achado de lesões coriorretinianas em uma criança com microcefalia deve aumentar a suspeita da forma autossômica recessiva da síndrome de microcefalia-coriorretinopatia, principalmente em casos com padrão atípico de fundo de olho e consanguinidade. O diagnóstico preciso é essencial para correta avaliação clínica e aconselhamento genético dos pacientes e suas famílias.

Tumor size and prognosis in patients with Wilms tumor / Tamanho tumoral e prognóstico em pacientes portadores de tumor de Wilms

OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ) and before preoperative chemotherapy (TVBPQ) with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ>500mL and the difference between the TVBPQ and TVAPQ (p=0.015) and histologic types of risk (p=0.008). It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037). When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013), i.e., for each increase of 10mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable. .

OBJETIVO: Investigar a relação entre o volume do tumor após a quimioterapia pré-operatória (VTPOS) e antes da quimioterapia pré-operatória (VTPRE) com sobrevida geral aos dois e cinco anos e tempo de vida. MÉTODOS: A amostra foi composta por pacientes consecutivos avaliados de 1989 a 2009, em um serviço de onco-hematologia. Os dados clínicos, histológicos e volumétricos foram coletados a partir dos registros médicos. Para análise, usaram-se os testes qui-quadrado, Kaplan-Meier, log-rank e regressão de Cox. RESULTADOS: A amostra foi composta de 32 pacientes, 53,1% do sexo masculino, com mediana de idade ao diagnóstico de 43 meses. Houve associação significativa entre VTPOS >500 mL e a diferença entre o VTPRE e VTPOS (p=0,015) e os tipos histológicos de risco (p=0,008). Verificou-se também uma associação entre a diferença entre o VTPRE e VTPOS e o tumor de predomínio estromal (p=0,037). Quando se avaliou o VTPOS de todos os pacientes, sem um ponto de corte definido, observou-se associação dessa variável com o tempo de vida (p=0,013), isto é, para cada aumento de 10 mL no VTPOS houve um aumento médio de 2% no risco de morte. CONCLUSÕES: Embora os resultados indiquem que o VTPOS poderia ser considerado um preditor isolado de mau prognóstico, independentemente do ponto de corte sugerido na literatura, mais estudos são necessários para substituir a histologia e estadiamento pelo tamanho do tumor como melhor variável prognóstica. .

[Tumor size and prognosis in patients with Wilms tumor]. / Tamanho tumoral e prognóstico em pacientes portadores de tumor de Wilms.

OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ) and before preoperative chemotherapy (TVBPQ) with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ >500 mL and the difference between the TVBPQ and TVAPQ (p=0.015) and histologic types of risk (p=0.008). It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037). When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013), i.e., for each increase of 10 mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable.

Microcephaly-chorioretinopathy syndrome, autosomal recessive form. A case report.

CONTEXT: The autosomal recessive form of microcephaly-chorioretinopathy syndrome is a rare genetic condition that is considered to be an important differential diagnosis with congenital toxoplasmosis. CASE REPORT: Our patient was a seven-year-old white boy who was initially diagnosed with congenital toxoplasmosis. However, his serological tests for congenital infections, including toxoplasmosis, were negative. He was the first child of young, healthy and consanguineous parents (fourth-degree relatives). The parents had normal head circumferences and intelligence. The patient presented microcephaly and specific abnormalities of the retina, with multiple diffuse oval areas of pigmentation and patches of chorioretinal atrophy associated with diffuse pigmentation of the fundus. Ophthalmological evaluations on the parents were normal. A computed tomography scan of the child's head showed slight dilation of lateral ventricles and basal cisterns without evidence of calcifications. We did not find any lymphedema in his hands and feet. He had postnatal growth retardation, severe mental retardation and cerebral palsy. CONCLUSIONS: The finding of chorioretinal lesions in a child with microcephaly should raise suspicions of the autosomal recessive form of microcephaly-chorioretinopathy syndrome, especially in cases with an atypical pattern of eye fundus and consanguinity. A specific diagnosis is essential for an appropriate clinical evaluation and for genetic counseling for the patients and their families.

45,X/46,XY mosaicism: report on 14 patients from a Brazilian hospital. A retrospective study / Mosaicismo 45,X/46,XY: relato de 14 pacientes de um hospital do Brasil. Um estudo retrospectivo

CONTEXT AND OBJECTIVE: 45,X/46,XY mosaicism, or mixed gonadal dysgenesis, is considered to be a rare disorder of sex development. The aim of our study was to investigate the clinical and cytogenetic characteristics of patients with this mosaicism. DESIGN AND SETTING: A retrospective study in a referral hospital in southern Brazil. METHODS: Our sample consisted of patients diagnosed at the clinical genetics service of a referral hospital in southern Brazil, from 1975 to 2012. Clinical and cytogenetic data were collected from the medical records. RESULTS: Fourteen patients were included in the sample, with ages at the first evaluation ranging from 2 days to 38 years. Nine of them had female sex of rearing and five, male. Regarding the external genitalia, most were ambiguous (n = 10). One patient presented male phenotype and was treated for a history of azoospermia, while three patients presented female phenotype, of whom two had findings of Turner syndrome and one presented secondary amenorrhea alone. Some findings of Turner syndrome were observed even among patients with ambiguous genitalia. None presented gonadal malignancy. One patient underwent surgical correction for genital ambiguity and subsequent exchange of sex of rearing. Regarding cytogenetics, we did not observe any direct correlation between percentages of cell lines and phenotype. CONCLUSIONS: 45,X/46,XY mosaicism can present with a wide variety of phenotypes resulting from the involvement of different aspects of the individual. All these observations have important implications for early recognition of these patients and their appropriate management. .

CONTEXTO E OBJETIVO: O mosaicismo 45,X/46,XY, ou disgenesia gonadal mista, é considerado uma doença rara do desenvolvimento sexual. O objetivo do nosso estudo foi verificar as características clínicas e citogenéticas de pacientes com este mosaicismo. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo em um hospital de referência no sul do Brasil. MÉTODOS: Nossa amostra foi composta por pacientes diagnosticados em um serviço de genética clínica de um hospital de referência no sul do Brasil, no período de 1975 até 2012. Os dados clínicos e citogenéticos foram coletados a partir dos prontuários médicos. RESULTADOS: Catorze pacientes foram incluídos na amostra, idades na primeira avaliação variando de 2 dias a 38 anos. Nove deles apresentavam sexo feminino de criação e cinco, masculino. A genitália externa, na maioria, era ambígua (n = 10). O paciente com fenótipo masculino foi tratado por história de azoospermia, enquanto que das três pacientes do fenótipo feminino, duas apresentavam achados da síndrome de Turner e a outra, amenorreia secundária isolada. Alguns achados da síndrome de Turner foram observados mesmo entre pacientes com genitália ambígua. Nenhum deles apresentou neoplasia gonadal. Um paciente foi submetido à correção cirúrgica de ambiguidade genital e posterior troca de sexo de criação. Quanto à citogenética, não observamos correlação direta entre a porcentagem de linhas de células e o fenótipo. CONCLUSÕES: O mosaicismo 45,X/46,XY pode apresentar grande variedade de fenótipos resultantes do envolvimento de diferentes aspectos do indivíduo. Todas essas observações têm implicações importantes para o reconhecimento precoce desses pacientes e seu adequado manejo. .

45,X/46,XY mosaicism: report on 14 patients from a Brazilian hospital. A retrospective study.

CONTEXT AND OBJECTIVE: 45,X/46,XY mosaicism, or mixed gonadal dysgenesis, is considered to be a rare disorder of sex development. The aim of our study was to investigate the clinical and cytogenetic characteristics of patients with this mosaicism. DESIGN AND SETTING: A retrospective study in a referral hospital in southern Brazil. METHODS: Our sample consisted of patients diagnosed at the clinical genetics service of a referral hospital in southern Brazil, from 1975 to 2012. Clinical and cytogenetic data were collected from the medical records. RESULTS: Fourteen patients were included in the sample, with ages at the first evaluation ranging from 2 days to 38 years. Nine of them had female sex of rearing and five, male. Regarding the external genitalia, most were ambiguous (n = 10). One patient presented male phenotype and was treated for a history of azoospermia, while three patients presented female phenotype, of whom two had findings of Turner syndrome and one presented secondary amenorrhea alone. Some findings of Turner syndrome were observed even among patients with ambiguous genitalia. None presented gonadal malignancy. One patient underwent surgical correction for genital ambiguity and subsequent exchange of sex of rearing. Regarding cytogenetics, we did not observe any direct correlation between percentages of cell lines and phenotype. CONCLUSIONS: 45,X/46,XY mosaicism can present with a wide variety of phenotypes resulting from the involvement of different aspects of the individual. All these observations have important implications for early recognition of these patients and their appropriate management.

Wilms tumor: experience of a hospital in southern Brazil.

BACKGROUND: Wilms tumor (WT) is the most common renal malignancy of childhood. The aim of this study was to verify the epidemiological profile and prognosis of a sample of patients from Brazil and compare them to similar data from other Latin American studies. METHOD: The sample consisted of consecutive patients diagnosed with WT in an oncohematology service of a referral hospital in Southern Brazil, between 1989 and 2009. Clinical, radiological, pathological and survival data were collected from the medical records. Analysis was done using Excel and SPSS version 18.0. The significance level was set at P < 0.05. RESULTS: The final sample consisted of 45 patients. The male/female ratio was 1.25:1. Mean age at diagnosis was 43.9 months and all patients were of European descent. Thirty-three patients (73.3%) had both signs/symptoms of abdominal mass and hypertension. Malformation was observed in nine patients (20%) and there was one case of Fanconi's anemia (2.2%). Three patients had bilateral disease (6.7%). The majority of patients had stage III and IV (62.2%). Patients with malformation had an earlier age at diagnosis (P = 0.018) and a higher prevalence of bilateral disease (P = 0.044). Overall survival was 75%. Age at diagnosis was the only significant independent predictor associated with death. CONCLUSION: Death is closely related to late diagnosis in WT. Oncologic services should also be concerned about morbidity caused by therapeutic options in cases of late diagnosis, and the consequences for quality of life.

Trisomy 18 and neural tube defects.

BACKGROUND: Trisomy 18 or Edwards syndrome is a chromosomal abnormality characterized by a broad clinical picture and a limited survival. More than 130 different abnormalities have been described in these patients-among them are neural tube defects. METHODS: We verified the frequency and types of major neural tube defects observed among patients with trisomy 18. Our sample consisted of consecutive patients evaluated by a clinical genetics service of a referral hospital in southern Brazil between 1975 and 2008. Fisher's exact test (two-tailed) and chi-square test with Yates' correction were used to compare frequencies (P < 0.05 values were considered as significant). RESULTS: During the period of evaluation, we identified 50 patients with trisomy 18; 33 (66%) were female and age at the first evaluation ranged from 1 day to 16 years (median 14 days). One cell line with full trisomy 18 was the predominant cytogenetic finding (90%). Three patients (6%) had major neural tube defects, all females. These were two patients (4%) with encephaloceles and one (2%) with myelomeningocele. This last patient undergo to correction surgery on her first day of life. CONCLUSIONS: Our data, in accordance with the literature, support the idea that the presence of neural tube defects among patients with trisomy 18 is not coincidental (i.e., these defects are actually part of the spectrum of abnormalities presented in trisomy 18). Thus, the diagnosis of trisomy 18 should be considered in children with major neural tube defects, especially in the presence of other abnormalities or dysmorphisms.

Malformations detected by abdominal ultrasound in children with congenital heart disease.

BACKGROUND: Extracardiac malformations may be present in patients with congenital heart disease (CHD), bringing greater risk of comorbidity and mortality. OBJECTIVE: Verify frequency and types of abdominal abnormalities detected in children with and without CHD through abdominal ultrasound (AUS), compare the patients in relation to their dysmorphic/cytogenetic findings and perform an estimative of the cost-effectiveness of the screening through AUS. METHODS: We conducted a cross-sectional study with a control cohort. The cases consisted of patients with CHD admitted for the first time in a pediatric intensive care unit; the controls consisted of children without CHD who underwent AUS at the hospital shortly thereafter a case. All patients with CHD underwent AUS, high-resolution karyotype and fluorescence in situ hybridization (FISH) for microdeletion 22q11.2. RESULTS: AUS identified clinically significant abnormalities in 12.2% of the cases and 5.2% of controls (p= 0.009), with a power of significance of 76.6%. Most malformations with clinical significance were renal anomalies (10.4% in cases and 4.9% in controls; p= 0.034). In Brazil, the cost of an AUS examination for the Unified Health System is US$ 21. Since clinically significant abnormalities were observed in one in every 8.2 CHD patients, the cost to identify an affected child was calculated as approximately US$ 176. CONCLUSION: Patients with CHD present a significant frequency of abdominal abnormalities detected by AUS, an inexpensive and noninvasive diagnostic method with good sensitivity. The cost of screening for these defects is considerably lower than the cost to treat the complications of late diagnoses of abdominal malformations such as renal disease.

Malformações detectadas pelo ultrassom abdominal em crianças com cardiopatia congênita / Malformations detected by abdominal ultrasound in children with congenital heart disease

FUNDAMENTO: Malformações extracardíacas podem estar presentes em pacientes com cardiopatia congênita (CC), trazendo maior risco de comorbidade e mortalidade. OBJETIVO: Verificar a frequência e os tipos de anormalidades abdominais detectadas em crianças com e sem CC através do ultrassom abdominal (USA), comparar os pacientes quanto a seus achados dismórficos/citogenéticos e realizar uma estimativa do custo-benefício da triagem pelo USA. MÉTODOS: Foi realizado um estudo transversal com controle. Os casos consistiram de pacientes com CC admitidos pela primeira vez em uma unidade de terapia intensiva pediátrica; os controles consistiram de crianças sem CC submetidas ao USA no hospital logo após cada caso. Todos os pacientes com CC foram submetidos ao USA, ao cariótipo de alta resolução e à hibridização in situ fluorescente (FISH) para microdeleção 22q11.2. RESULTADOS: USA identificou anormalidades clinicamente significativas em 12,2% dos casos e em 5,2% dos controles (p = 0,009), com um poder de significância de 76,6%. A maioria das malformações com significado clínico foi de anomalias renais (10,4% nos casos e 4,9% nos controles, p = 0,034). No Brasil, o custo de um exame de USA pelo Sistema Único de Saúde é de 21 dólares. Uma vez que anormalidades clinicamente significativas foram observadas em um a cada 8,2 pacientes com CC, o custo para identificar uma criança afetada foi de 176 dólares. CONCLUSÃO: Pacientes com CC apresentam uma frequência significativa de anomalias detectadas pelo USA, um método diagnóstico barato e não invasivo, com boa sensibilidade. O custo da triagem para esses defeitos é consideravelmente menor que o custo para tratar as complicações do diagnóstico tardio de malformações abdominais, como a doença renal.

BACKGROUND: Extracardiac malformations may be present in patients with congenital heart disease (CHD), bringing greater risk of comorbidity and mortality. OBJECTIVE: Verify frequency and types of abdominal abnormalities detected in children with and without CHD through abdominal ultrasound (AUS), compare the patients in relation to their dysmorphic/cytogenetic findings and perform an estimative of the cost-effectiveness of the screening through AUS. METHODS: We conducted a cross-sectional study with a control cohort. The cases consisted of patients with CHD admitted for the first time in a pediatric intensive care unit; the controls consisted of children without CHD who underwent AUS at the hospital shortly thereafter a case. All patients with CHD underwent AUS, high-resolution karyotype and fluorescence in situ hybridization (FISH) for microdeletion 22q11.2. RESULTS: AUS identified clinically significant abnormalities in 12.2% of the cases and 5.2% of controls (p= 0.009), with a power of significance of 76.6%. Most malformations with clinical significance were renal anomalies (10.4% in cases and 4.9% in controls; p= 0.034). In Brazil, the cost of an AUS examination for the Unified Health System is US$ 21. Since clinically significant abnormalities were observed in one in every 8.2 CHD patients, the cost to identify an affected child was calculated as approximately US$ 176. CONCLUSION: Patients with CHD present a significant frequency of abdominal abnormalities detected by AUS, an inexpensive and noninvasive diagnostic method with good sensitivity. The cost of screening for these defects is considerably lower than the cost to treat the complications of late diagnoses of abdominal malformations such as renal disease.

Anormalidades de membros na trissomia do cromossomo 18: evidência para o diagnóstico precoce / Limb abnormalities on trisomy 18: evidence for early diagnosis

OBJETIVO: Verificar a frequência e os tipos de anormalidades de membros observadas entre pacientes com trissomia do cromossomo 18, ou síndrome de Edwards (SE). MÉTODO: A amostra foi constituída de pacientes consecutivos avaliados por um serviço de genética clínica no período entre 1975 e 2008. O resultado da análise citogenética, bem como os dados clínicos, foram coletados a partir dos prontuários médicos, dando-se ênfase aos seus achados de membros. Todos foram submetidos ao exame de cariótipo no mesmo laboratório. RESULTADOS: No período de avaliação, foram identificados 50 pacientes, 33 deles (66%) do sexo feminino, com idade na primeira avaliação variando de 1 dia a 16 anos (mediana de 14 dias). A linhagem única com trissomia livre do cromossomo 18 foi a alteração cromossômica predominante (90%). Mosaicismo foi verificado em 10% dos casos. A anormalidade predominante de membros superiores observada na amostra (n = 50) foi o punho cerrado com sobreposição dos dedos (70%). Outras alterações frequentes incluíram a prega palmar única (42%) e a hipoplasia das unhas (36%). Anormalidades radiais foram observadas em 11 pacientes (22%). Quanto aos membros inferiores, a hipoplasia de unhas foi a alteração mais comum (58%), seguida do pé em mata-borrão com calcâneo proeminente (50%). Um dos pacientes possuía ainda ectrodactilia unilateral. CONCLUSÕES: Apesar da descrição clássica, as anormalidades de membros podem ser bastante variáveis na SE. Alguns pacientes podem ainda apresentar alterações não usuais, como defeitos radiais e ectrodactilia. Esses achados são de extrema importância para a suspeita e a identificação clínica precoce dos pacientes com a SE.

OBJECTIVE: To assess the frequency and types of limb abnormalities observed among patients with trisomy 18, or Edwards syndrome (ES). METHOD: The sample consisted of consecutive patients evaluated by a clinical genetics service in the period from 1975 to 2008. The results of the cytogenetic analysis, as well as the clinical data were retrieved from the medical records, with special attention to limb abnormalities findings. All the karyotype analysis was performed at the same laboratory. RESULTS: During the study period, 50 patients were identified, 33 (66%) of them females, with ages at the first evaluation ranging from 1 day to 16 years (median 14 days). The single lineage with free trisomy 18 was the most frequent chromosomal disorder (90%). Mosaicism was observed in 10% of the cases. Clenched fist with overlapping fingers was the predominant anomaly of the upper limbs (70%). Other common disorders included the single palmar crease (42%) and hypoplastic nails (36%). Radial abnormalities were found in 11 patients (22%). As for the lower limbs, hypoplastic nails were the most common abnormality (58%), followed by the rocker bottom foot with prominent calcaneus (50%). One patient had unilateral ectrodactyly as well. CONCLUSIONS: Despite the classical description, limb anomalies can be much variable in ES. Some patients may show unusual abnormalities, such as radial defects and ectrodactyly. These findings are extremely important for the clinical suspicion and early identification of patients with ES.

Limb abnormalities on trisomy 18: evidence for early diagnosis.

OBJECTIVE: To assess the frequency and types of limb abnormalities observed among patients with trisomy 18, or Edwards syndrome (ES). METHOD: The sample consisted of consecutive patients evaluated by a clinical genetics service in the period from 1975 to 2008. The results of the cytogenetic analysis, as well as the clinical data were retrieved from the medical records, with special attention to limb abnormalities findings. All the karyotype analysis was performed at the same laboratory. RESULTS: During the study period, 50 patients were identified, 33 (66%) of them females, with ages at the first evaluation ranging from 1 day to 16 years (median 14 days). The single lineage with free trisomy 18 was the most frequent chromosomal disorder (90%). Mosaicism was observed in 10% of the cases. Clenched fist with overlapping fingers was the predominant anomaly of the upper limbs (70%). Other common disorders included the single palmar crease (42%) and hypoplastic nails (36%). Radial abnormalities were found in 11 patients (22%). As for the lower limbs, hypoplastic nails were the most common abnormality (58%), followed by the rocker bottom foot with prominent calcaneus (50%). One patient had unilateral ectrodactyly as well. CONCLUSIONS: Despite the classical description, limb anomalies can be much variable in ES. Some patients may show unusual abnormalities, such as radial defects and ectrodactyly. These findings are extremely important for the clinical suspicion and early identification of patients with ES.