Mothers of children with Down syndrome: a clinical and epidemiological study.

Down syndrome is the main genetic cause of intellectual disability. Many studies describe the clinical characteristics of DS patients; however, few have investigated the clinical profile of mothers who have children with DS. Advanced maternal age (≥ 35 years old) is a risk factor for DS. Although there is an overall increase in pregnancies among women with advanced maternal age, there is still a lack of awareness of the increased risk of aneuploidy. Here, we reported the clinical and epidemiological profile of DS children and their mothers in a public reference hospital in the State of Rio de Janeiro, Brazil. For data collection, we performed a face-to-face interview guided by a structured questionnaire with closed-ended questions. A total of 344 individuals, 172 mothers and their DS children, were included in this study. Our results show that 56% of the mothers sampled were ≥ 35 years of age at childbirth. Although 98% of them received prenatal care, only 4% obtained a prenatal diagnosis of DS. Most mothers reported not drinking alcohol or smoking cigarettes during pregnancy. Furthermore, 91% of women took prenatal vitamins and supplements; however, 47% were not aware of their benefits for a healthy pregnancy. Given the strict correlation between advanced maternal age and DS, prenatal care should include genetic counseling for women over 35 years of age. This study highlights the importance of prenatal care and the urgent need for better DS screening allowing for immediate postnatal care, positively impacting the life expectancy of these patients.

Clinical Profile Among Brazilian Mucopolysaccharidosis type II Patients: Subgroup Analysis from the Hunter Outcome Survey

Abstract Mucopolysaccharidosis type II (MPS II) is a rare genetic, multiorgan disease. Little information about the Brazilian context is available to date; thus, this descriptive subgroup analysis was conducted on Brazilian data from the Hunter Outcome Survey (HOS), including clinical characteristics among MPS II patients from Brazil. HOS is a global, multi-center, long-term, observational registry of patients with MPS II (NCT03292887). Variables related to organ system involvement, signs and symptoms, surgical procedures and survival among Brazilian patients were extracted from HOS database. Data from 153 Brazilian patients with MPS II were analyzed. Musculoskeletal (96.6%), abdomen/gastrointestinal (95.2%), neurological (88.7%), pulmonary (86.2%), and ear (81.3%) were the most frequently observed organ/systems involved. Regarding signs and symptoms, the most prevalent symptom was coarse facial features consistent with the disease (94.6%), followed by joint stiffness and limited function (89.3%), hernia (84.2%) and hepatomegaly (82.2%). Median survival time was 22.0 years, and the major cause of death was respiratory failure (31.8%). These data may be helpful to understand disease characteristics and to help improve the quality of MPS II patient care in Brazil.

Aurora kinase genetic polymorphisms: an association study in Down syndrome and spontaneous abortion.

Aneuploidies, such as Down syndrome (DS), are the leading cause of pregnancy loss. Abnormalities in aurora kinase proteins result in genomic instability and aneuploidy, mainly in tumors. Thus, polymorphisms in Aurora kinase genes could influence the occurrence of DS and spontaneous abortion. A case-control study was conducted including 124 mothers of DS children (DSM) and 219 control mothers (CM) to investigate DS risk according to AURKA and AURKC polymorphisms. Genotyping was performed using TaqMan real-time PCR. The minor allele frequency (MAF) observed in AURKA rs2273535 was, respectively, 0.23 in DSM and 0.20 in CM, whereas the frequency of the AURKC rs758099 T allele was 0.32 in case and 0.33 in control mothers. Statistical analysis showed no significant difference in the distribution of genotypes and allele frequencies between DSM and CM. According to previous history of spontaneous abortion, the AURKA rs2273535 genotypes (TT + AT vs. AA: OR 2.54, 95% CI 1.13-5.71, p = 0.02; AT vs. AA: OR 2.39, 95% CI 1.03-5.51, p = 0.04; T vs. A: OR 2.08, 95% CI 1.12-3.90, p = 0.02) and AURKC rs758099 (TT vs. CC: OR 4.34, 95% CI 1.03-18.02, p = 0.04; TT + CT vs. CC: OR 2.52, 95% CI 1.02-6.23, p = 0.04; T vs. C: OR 2.03, 95% CI 1.09-3.80, p = 0.02) were observed as risk factors for spontaneous abortion in case mothers. Our study suggests a possible relationship between AURKA/AURKC variants and increased risk of spontaneous abortion within Down syndrome mothers.

Health-related quality of life in paediatric patients with intoxication-type inborn errors of metabolism: Analysis of an international data set.

Acute intoxication-type inborn errors of metabolism (IT-IEM) such as urea cycle disorders and non-acute IT-IEM such as phenylketonuria have a major impact on paediatric patients' life. Patients have to adhere to a strict diet but may face neurocognitive impairment and - in acute diseases - metabolic decompensations nevertheless. Research on the subjective burden of IT-IEM remains sparse. Studies with appropriate sample sizes are needed to make valid statements about health-related quality of life (HrQoL) in children and adolescents with IT-IEM. Six international metabolic centres contributed self-reports and proxy reports of HrQoL (assessed with the Paediatric Quality of Life Inventory) to the final data set (n = 251 patients; age range 2.3-18.8 years). To compare HrQoL of the patient sample with norm data and between acute and non-acute IT-IEM, t tests were conducted. To examine the influence of child age, sex, diagnosis and current dietary treatment on HrQoL, multiple linear regression analyses were conducted. Self-reports and proxy reporst showed significantly lower HrQoL total scores for children with IT-IEM compared to healthy children. Current dietary treatment significantly predicted lower proxy reported total HrQoL. Children with non-acute IT-IEM reported significantly lower psychosocial health and emotional functioning than children with acute IT-IEM. The patient sample showed significantly impaired HrQoL and a diet regimen remains a risk factor for lower HrQoL. Differences in HrQoL between acute and non-acute IT-IEM subgroups indicate that factors beyond symptom severity determine the perception of disease burden. Identifying these factors is of crucial importance to develop and implement appropriate interventions for those in need.

Hereditary angioedema: a prospective study of a Brazilian single-center cohort.

BACKGROUND: Hereditary angioedema (HAE) is rare and still underdiagnosed in some countries. We aimed to describe HAE diagnosis and sociodemographic and clinical features in patients with HAE due to C1 inhibitor deficiency (HAE-C1-INH) followed up at a tertiary-level center in Rio de Janeiro, Brazil. METHODS: A descriptive, cross-sectional study with prospective data collection of 138 Brazilian patients with HAE was performed. From the total, 107 patients with HAE-C1-INH were selected. Data were assessed based on a specific questionnaire. RESULTS: One hundred and five patients had HAE type I (76.1%), and two had HAE type II (1.4%). Seventy-two were female (67.3%), and 35 were male  (32.7%). Mean age was 38.0 ± 15.0 years (range: 12-73 years). A long delay (17.7 ± 12.6 years) until diagnosis was observed. About 86.9% had a familial history. Cutaneous edema (95.8%), abdominal pain (88.5%), and laryngeal edema (65.6%) were the most frequent symptoms. Triggering factors (95.8%) and prodromal symptoms (47.9%) were referred. Attacks were severe in 55.1% and moderate in 24.3%. Eleven (10.3%) were asymptomatic. HAE attacks were more frequent and severe (P = 0.021) in females. CONCLUSIONS: We observed a considerable delay in diagnosis, even with familial history. The severity of HAE attacks, especially in females, highlights the need for an awareness of disease by gynecologists and obstetricians. Screening of familial members, including asymptomatic individuals, is critical for earlier diagnosis. Regional evaluation of patient profiles can be helpful to draw more attention about HAE and to improve quality of life.

Genotype-phenotype correlations and BH4 estimated responsiveness in patients with phenylketonuria from Rio de Janeiro, Southeast Brazil.

BACKGROUND: Genetic heterogeneity and compound heterozygosis give rise to a continuous spectrum of phenylalanine hydroxylase deficiency and metabolic phenotypes in phenylketonuria (PKU). The most used parameters for evaluating phenotype in PKU are pretreatment phenylalanine (Phe) levels, tolerance for dietary Phe, and Phe overloading test. Phenotype can vary from a "classic" (severe) form to mild hyperphenylalaninemia, which does not require dietary treatment. A subset of patients is responsive to treatment by the cofactor tetrahydrobiopterin (BH4 ). Genotypes of PKU patients from Rio de Janeiro, Brazil, were compared to predicted and observed phenotypes. Genotype-based estimations of responsiveness to BH4 were also conducted. METHODS: Phenotype was defined by pretreatment Phe levels. A standard prediction system based on arbitrary assigned values was employed to measure genotype-phenotype concordance. Patients were also estimated as BH4 -responders according to the responsiveness previously reported for their mutations and genotypes. RESULTS: A 48.3% concordance rate between genotype-predicted and observed phenotypes was found. When the predicted phenotypes included those reported at the BIOPKU database, the concordance rate reached 77%. A total of 18 genotypes from 30 patients (29.4%) were estimated as of potential or probable BH4 responsiveness. Inconsistencies were observed in genotypic combinations including the common "moderate" mutations p.R261Q, p.V388M, and p.I65T and the mild mutations p.L48S, p.R68S, and p.L249F. CONCLUSION: The high discordance rate between genotype-predicted and observed metabolic phenotypes in this study seems to be due partially to the high frequency of the so-called "moderate" common mutations, p.R261Q, p.V388M, and p.I65T, which are reported to be associated to erratic or more severe than expected metabolic phenotypes. Although our results of BH4 estimated responsiveness must be regarded as tentative, it should be emphasized that genotyping and genotype-phenotype association studies are important in selecting patients to be offered a BH4 overload test, especially in low-resource settings like Brazil.

Benefits from using an ankle-foot orthosis in children with myelomeningocele / Benefícios do uso da órtese tornozelo-pé nas crianças com mielomeningocele

Myelomeningocele (MMC) or spina bifida is a defect of the neural tube in which the spinal cord, its envelopes (meninges), and vertebral arches develop abnormally in the beginning of gestation, and owing to this failure of closure there appear a series of congenital defects and associated comorbidies, impairing in several aspects the functioning of the life of children with MMC. The congenital clubfoot has been found the most common orthopaedic anomaly in patients with MMC. The ankle-foot orthosis (AFO) is an orthopaedic device commonly used by these children to minimize the sequelae caused by this anomaly. OBJECTIVE: Identify the functional benefits brought about by the use of the AFO to children with MMC, as reported by their guardians. METHOD: Descriptive, transversal study. Convenience sample consisting of 25 guardians of children with MMC who were using/had used an AFO. RESULTS: Eighty percent of the guardians have reported at least one benefit brought about by the use of the AFO, among them: improvement in foot position (68%), foot growth (40%), improvement in foot balance (32%), and balance sitting position (15%). CONCLUSION: The use of the AFO by children with MMC can provide several benefits reported by their guardians.

A mielomeningocele (MMC) ou espinha bífida é um defeito do tubo neura no qual a medula espinal, seus envoltórios (meninges) e os arcos vertebrais desenvolvem-se anormalmente no início da gestação e, como consequências, temos uma série de defeitos congênitos e comorbidades associadas prejudicando a funcionalidade em diversos aspectos da vida das crianças com MMC. O pé torto congênito foi apontado como a anomalia ortopédica mais comum nos pacientes com MMC e a órtese tornozelo-pé (OTP) é um aparelho ortopédico que pode ser usado nessas crianças para amenizar as sequelas geradas por essa anomalia. OBJETIVO: Identificar os benefícios funcionais trazidos pelo uso da OTP em crianças com MMC relata-dos pelos seus responsáveis. MÉTODO: Estudo descritivo, transversal. Amostra de conveniência composta por responsáveis de 25 crianças com MMC que usavam/usaram a OTP que responderam a uma entrevista estruturada que contemplava as variáveis estudadas. RESULTADOS: Oitenta por cento dos responsáveis relataram pelo menos um benefício causado pelo uso da OTP, dentre eles: melhorou a postura do pé (68%), o pé cresceu (40%), melhorou o equilíbrio em pé (32%), melhorou o equilíbrio sentado (15%). CONCLUSÃO: O uso da OTP em crianças com MMC pode proporcionar benefícios identificados pelos responsáveis.

Betaine-homocysteine methyltransferase 742G>A polymorphism and risk of down syndrome offspring in a Brazilian population.

Down syndrome (DS) is the most common form of mental retardation of genetic etiology. Several polymorphisms in genes involved with the folic acid cycle have been associated to the risk of bearing a DS child; however, the results are controversial. Betaine-homocysteine methyltransferase (BHMT) is a key enzyme of folate pathway, and catalyzes the remethylation of homocysteine into methionine. Recent studies suggest that the polymorphism BHMT 742G>A may be associated with a decreased risk of having a DS child. We herein investigate the association of this polymorphism with the occurrence of DS in a Brazilian population. We have genotyped 94 mothers of DS infants (DSM) and 134 control mothers (CM) for this polymorphism through PCR-RFLP, and found significant differences for both BHMT 742G>A genotype (P=0.04) and allele (P=0.03) frequencies between DSM and CM. The observed genotypic frequencies were GG=0.45; GA=0.45 and AA=0.10 in CM, and GG=0.54; GA=0.38 and AA=0.02 in DSM. Allelic frequencies were G=0.68 and A=0.32 in CM and G=0.78 and A=0.22 in DSM. The presence of the mutant BHMT 742 A allele decreases 40% the risk of bearing a DS child (OR=0.61; 95% CI: 0.40-0.93; P=0.03), and the risk is diminished up to >80% in association with the homozygous genotype (OR=0.17; 95% CI: 0.04-0.80; P=0.01). Our results indicate that women harboring the single nucleotide polymorphism BHMT 742G>A have a decreased risk of a DS pregnancy, and further studies are necessary to confirm this protective effect.

Clinical characteristics of alopecia areata in Down syndrome.

This study was undertaken to better understand clinical characteristics, environmental and physical events in Down syndrome (DS) and alopecia areata (AA). This cross-sectional study included 18 DS patients who were currently presenting or had presented AA. We evaluated gender, age, location and type of AA, presence of autoimmune disease or atopy, AA in first-degree relatives, and environmental, physical, and clinical intercurrences. The mean age of study subjects was 11.6 (SD ± 5.5) years and mean age at AA onset 7.2 (2.5 to 15.2) years. The duration of alopecia episodes varied, with a mean of 2.7 (0.1 to 18.7) years. Recurrence of AA was reported in 27.7% (5/18) of subjects, with a mean number of recurrences of 3.6. Localized type AA was seen in 83.4% of individuals, with the most frequent location on the scalp (100%). Seven of the individuals presented atopy. Fourteen individuals had undergone environmental and/or clinical intercurrences. In conclusion, the most frequent presentation of AA in DS is the non-recurrent, localized form on the scalp, with a varied period of duration. Changes in the individuals' routine occurred in more than half of the study group. We suggest further studies of the psychology and immunogenetics in the etiopathology of AA in DS.

Herpes simples: atualização clínica, epidemiológica e terapêutica / Herpes simplex: clinical update, epidemiology and therapeutics

Herpes é uma infecção causada por dois vírus da família Herpesviridae (herpes simples tipos 1 e 2; HSV-1 e HSV-1), que apresenta curso clínico variável e para o qual atualmente não existe cura. As manifestações da infecção por HSV-1 incluem herpes simples orofacial primário e recorrente, enquanto as do HSV-2 em geral ocorrem na forma de herpes simples genital, embora casos de lesões genitais pelo HSV-1 e orais pelo HSV-2 possam ocorrer. As infecções pelo vírus herpes simples (HSV-1 e HSV-2) representam as doenças sexualmente transmissíveis mais comuns a nível global, alcançando uma soroprevalência de 80% em adultos. Nesta revisão da literatura, abordaremos os aspectos clínicos da infecção pelo HSV, incluindo a epidemiologia, etiologia, manifestações clínicas, métodos diagnósticos e tratamento, bem como uma breve descrição da imunogenética da infecção pelo HSV

Herpes is an infection caused by two viruses in the Herpesviridae family (herpes simplex types 1 and 2; HSV-1 and HSV-2), which presents a variable clinical course and for which there is currently no cure. The manifestations of HSV-1 infection include primary and recurrent orofacial herpes simplex, while HSV-2 infection usually manifests in the form of genital herpes simplex, although cases of genital lesions from HSV-1 infection and oral lesions form HSV-2 infection can occur. Infections by the herpes simplex virus (HSV-1 and HSV-2) represent one of the most common sexually transmitted diseases globally, reaching a serum prevalence of 80% in adults. In this review of the literature, we discuss the clinical aspects of HSV infection, including epidemiology, etiology, clinical manifestations, diagnosis and treatment, as well as a brief description of the immunogenetics of HSV infection.

A novel nonsense mutation in KDM5C/JARID1C gene causing intellectual disability, short stature and speech delay.

Mutations in the Jumonji AT-rich interactive domain 1C (JARID1C/SMCX/KDM5C) gene, located at Xp11.22, are emerging as frequent causes of X-linked intellectual disability (XLID). KDM5C encodes for a member of an ARID protein family that harbors conserved DNA-binding motifs and acts as a histone H3 lysine 4 demethylase, suggesting a potential role in epigenetic regulation during development, cell growth and differentiation. In this study, we describe clinical and genetic findings of a Brazilian family co-segregating a novel nonsense mutation (c.2172C>A) in exon 15 of KDM5C gene with the intellectual disability phenotype. The transition resulted in replacement of the normal cysteine by a premature termination codon at position 724 of the protein (p.Cys724X), leading to reduced levels of KDM5C transcript probably due to nonsense mediated mRNA decay. The clinical phenotype of the proband, who has two affected brothers and a mild cognitively impaired mother, consisted of short stature, speech delay, hyperactivity, violent behavior and high palate, besides severe mental retardation. Our findings extend the number of KDM5C mutations implicated in XLID and highlight its promise for understanding neural function and unexplained cases of XLID.

Proposta de acolhimento diferenciado a pais de crianças com queixas de alterações de linguagem / Propuesta de acogimiento diferenciado a padres de niños con queja de problemas de lenguaje / Proposal of differentiated care to parents of children with complaints of language alterations

Introdução: Tem sido crescente na clínica fonoaudiológica, no âmbito público ou privado, a demanda por atendimento, a crianças com queixas como: “não fala”, “fala pouco”, “fala errado”, ou“apresenta fala ininteligível”. No Sistema Único de Saúde, a possibilidade de acolher essa demanda constitui-se uma questão relevante em conformidade com as políticas públicas de saúde, baseada nos conceitos de promoção, prevenção e acolhimento. Objetivo: Verificar a eficácia de um procedimento de acolhimento diferenciado, com fins preventivos, a pais de crianças com queixas de alterações de linguagem oral, que aguardam por atendimento fonoaudiológico no Sistema Único de Saúde. Metódo: Trata-se de pesquisa quanti-qualitativa. Participaram da pesquisa seis famílias em fila de espera numa UBS de São Paulo. Foram utilizados 5 instrumentos: 1-Entrevista Inicial com os pais; 2- Avaliação de Linguagem; 3-Questionário de Habilidades e Dificuldades Comunicativas dos Pais; 4-Protocolo de Observação das Atitudes Comunicativas dos Pais preenchido a partir da filmagem de uma atividade lúdica entre pais e respectivos filho(a) e 1 instrumento que norteou a construção do acolhimento diferenciado: 5- Protocolo de Ações Favoráveis e Desfavoráveis à Comunicação, a Brincadeiras e aos Hábitos Orais. Após 3 meses foram reaplicados os instrumentos 2, 3 e 4, para verificar se houveram mudanças. Resultados: Após o acolhimento diferenciado todas as famílias referiram compreender melhor a fala das crianças. Observou-se aumento geral das atitudes comunicativas favoráveis do tipo: reformulações no discurso; enunciados de continuidade; solicitação de esclarecimento e decréscimo nas atitudes desfavoráveis. Isto mostrou que houve uma repercussão positiva na dialogia, nas interações e, conseqüente, nas habilidades comunicativas das crianças. Conclusão: os resultados apontam que a proposta de acolhimento diferenciado foi efetiva como um dispositivo clínico fonoaudiológico em saúde pública.

troduction: It has been increasing in private or public Speech-Language and Hearing clinicsdemands for care to children with complaints like: “do not talk”; “speaks little”; “speaks wrong” or“presents unintelligible productions”. The possibility to accept that demand in the National HealthSystem is a relevant issue in accordance with public health policies based on the concepts of promotion,prevention and care. Goal: Check the efficacy of differentiated care procedure, with preventive purposes, to parents of children with language alterations complaints waiting for speech therapy in the NationalHealth System. Method: Quantitative and qualitative research with participation of six families waitingfor speech therapy in a Health Unit in São Paulo - Brasil. Five instruments were used: 1- Initial Interviewwith parents; 2- Language Evaluation; 3- Communicative Abilities and Difficulties Questionnaire forParents; 4- Communicative Attitudes Observation Protocol for Parents filled in from the filming of aplay activity between parents and their children and an instrument that guided the construction of thedifferentiated care: 5- Favorable and Unfavorable Actions to Communication, Play and Oral Habits.After 3 months the 2, 3 and 4 instruments were re-applied, to check whether there were changes. Results:After the differentiated care all families reported a better understanding of their children’s speech. Ageneral increasing of favorable attitudes like: discourse reformulations, continuity enunciations, requestsfor clarification was observed, and also a decrease in unfavorable attitudes. That showed a positiveimpact on the dialogism, on the resulting interactions and communicative of the children. Conclusion:The results show that the proposed differentiated care was effective as a Speech-Language and Hearingclinical device in public health and may establish new care practices family-centered and centered inthe commitments of...

troducción: Ha sido creciente en la clínica fonoaudiológica, sea en la esfera publica o privada,la búsqueda por atención clínica a niños con quejas como: “no habla”, “habla poco”, “habla conerrores”, o “presenta habla ininteligible”. En el Sistema Único de Salud (SUS) brasileño, la posibilidadde acoger a esa demanda es una cuestión relevante de acuerdo con las políticas de salud basadas en losconceptos de promoción, prevención y acogimiento. Objetivo: Verificar la eficacia de un procedimientode acogimiento diferente, con fines de prevención, a padres de niños con queja de problemas de lenguajeoral, que esperan por atención clínica fonoaudiológica en el Sistema Único de Salud brasileño.Método: Investigación cuanti-cualitativa. Participaron seis familias que estaban en una fila de esperaen una Unidad Básica de Salud de San Pablo – Brasil. Se utilizó 5 instrumentos para coger los datos:1- Entrevista Inicial con los Padres; 2- Evaluación de Lenguaje; 3- Cuestionario de Habilidades yDificultades Comunicativas de los Padres; 4- Protocolo de Observación de Actitudes Comunicativasde los Padres, llenado a partir de la filmación de una actividad lúdica desarrollada entre los padresy 1 instrumento que orientó la construcción del acogimiento diferenciado: 5- Protocolo de AccionesFavorables y Desfavorables a la Comunicación, al Juego y a los Hábitos Orales. Después de 3 mesesfueron aplicados de nuevo los instrumentos 2, 3 y 4, para averiguar si hubieron cambios. Resultados:Después del acogimiento diferenciado todas las familias refirieron comprender mejor el habla de losniños. Se observó aumento general de actitudes comunicativas favorables del tipo: reformulaciones deldiscurso; enunciados de continuidad; solicitaciones de esclarecimiento y disminución en las actitudesdesfavorables. Esto evidenció que hubo una repercusión positiva en la dialogia, en las interacciones yconsecuentemente en las habilidades comunicativas de los niño...

Proposta de acolhimento diferenciado a pais de crianças com queixas de alterações de linguagem / Proposal of Differentiated Care to Parents of Children with Complaints of Language Alterations Propuesta de Acogimiento Diferenciado a Padres de Niños con Queja de Problemas de Lenguaje

Introdução: Tem sido crescente na clínica fonoaudiológica, no âmbito público ou privado, a demanda por atendimento, a crianças com queixas como: “não fala”, “fala pouco”, “fala errado”, ou“apresenta fala ininteligível”. No Sistema Único de Saúde, a possibilidade de acolher essa demanda constitui-se uma questão relevante em conformidade com as políticas públicas de saúde, baseada nos conceitos de promoção, prevenção e acolhimento. Objetivo: Verificar a eficácia de um procedimento de acolhimento diferenciado, com fins preventivos, a pais de crianças com queixas de alterações de linguagem oral, que aguardam por atendimento fonoaudiológico no Sistema Único de Saúde. Metódo: Trata-se de pesquisa quanti-qualitativa. Participaram da pesquisa seis famílias em fila de espera numa UBS de São Paulo. Foram utilizados 5 instrumentos: 1-Entrevista Inicial com os pais; 2- Avaliação de Linguagem; 3-Questionário de Habilidades e Dificuldades Comunicativas dos Pais; 4-Protocolo de Observação das Atitudes Comunicativas dos Pais preenchido a partir da filmagem de uma atividade lúdica entre pais e respectivos filho(a) e 1 instrumento que norteou a construção do acolhimento diferenciado: 5- Protocolo de Ações Favoráveis e Desfavoráveis à Comunicação, a Brincadeiras e aos Hábitos Orais. Após 3 meses foram reaplicados os instrumentos 2, 3 e 4, para verificar se houveram mudanças. Resultados: Após o acolhimento diferenciado todas as famílias referiram compreender melhor a fala das crianças. Observou-se aumento geral das atitudes comunicativas favoráveis do tipo: reformulações no discurso; enunciados de continuidade; solicitação de esclarecimento e decréscimo nas atitudes desfavoráveis. Isto mostrou que houve uma repercussão positiva na dialogia, nas interações e, conseqüente, nas habilidades comunicativas das crianças. Conclusão: os resultados apontam que a proposta de acolhimento diferenciado foi efetiva como um dispositivo clínico fonoaudiológico em saúde pública.(AU)

Introduction: It has been increasing in private or public Speech-Language and Hearing clinicsdemands for care to children with complaints like: “do not talk”; “speaks little”; “speaks wrong” or“presents unintelligible productions”. The possibility to accept that demand in the National HealthSystem is a relevant issue in accordance with public health policies based on the concepts of promotion,prevention and care. Goal: Check the efficacy of differentiated care procedure, with preventive purposes, to parents of children with language alterations complaints waiting for speech therapy in the NationalHealth System. Method: Quantitative and qualitative research with participation of six families waitingfor speech therapy in a Health Unit in São Paulo - Brasil. Five instruments were used: 1- Initial Interviewwith parents; 2- Language Evaluation; 3- Communicative Abilities and Difficulties Questionnaire forParents; 4- Communicative Attitudes Observation Protocol for Parents filled in from the filming of aplay activity between parents and their children and an instrument that guided the construction of thedifferentiated care: 5- Favorable and Unfavorable Actions to Communication, Play and Oral Habits.After 3 months the 2, 3 and 4 instruments were re-applied, to check whether there were changes. Results:After the differentiated care all families reported a better understanding of their children’s speech. Ageneral increasing of favorable attitudes like: discourse reformulations, continuity enunciations, requestsfor clarification was observed, and also a decrease in unfavorable attitudes. That showed a positiveimpact on the dialogism, on the resulting interactions and communicative of the children. Conclusion:The results show that the proposed differentiated care was effective as a Speech-Language and Hearingclinical device in public health and may establish new care practices family-centered and centered inthe commitments of...(AU)

Introducción: Ha sido creciente en la clínica fonoaudiológica, sea en la esfera publica o privada,la búsqueda por atención clínica a niños con quejas como: “no habla”, “habla poco”, “habla conerrores”, o “presenta habla ininteligible”. En el Sistema Único de Salud (SUS) brasileño, la posibilidadde acoger a esa demanda es una cuestión relevante de acuerdo con las políticas de salud basadas en losconceptos de promoción, prevención y acogimiento. Objetivo: Verificar la eficacia de un procedimientode acogimiento diferente, con fines de prevención, a padres de niños con queja de problemas de lenguajeoral, que esperan por atención clínica fonoaudiológica en el Sistema Único de Salud brasileño.Método: Investigación cuanti-cualitativa. Participaron seis familias que estaban en una fila de esperaen una Unidad Básica de Salud de San Pablo – Brasil. Se utilizó 5 instrumentos para coger los datos:1- Entrevista Inicial con los Padres; 2- Evaluación de Lenguaje; 3- Cuestionario de Habilidades yDificultades Comunicativas de los Padres; 4- Protocolo de Observación de Actitudes Comunicativasde los Padres, llenado a partir de la filmación de una actividad lúdica desarrollada entre los padresy 1 instrumento que orientó la construcción del acogimiento diferenciado: 5- Protocolo de AccionesFavorables y Desfavorables a la Comunicación, al Juego y a los Hábitos Orales. Después de 3 mesesfueron aplicados de nuevo los instrumentos 2, 3 y 4, para averiguar si hubieron cambios. Resultados:Después del acogimiento diferenciado todas las familias refirieron comprender mejor el habla de losniños. Se observó aumento general de actitudes comunicativas favorables del tipo: reformulaciones deldiscurso; enunciados de continuidad; solicitaciones de esclarecimiento y disminución en las actitudesdesfavorables. Esto evidenció que hubo una repercusión positiva en la dialogia, en las interacciones yconsecuentemente en las habilidades comunicativas de los niño...(AU)

IGF-I and IGF Binding Protein-3 Generation Tests and Response to Growth Hormone in Children with Silver-Russell Syndrome.

Objectives. To evaluate, in children with Silver-Russell Syndrome, the response to the IGF-I and IGFBP-3 generation test and compare results to the growth response after 6 months of rhGH. Methods. Eight children (6 males), with a mean age of 5.71 ± 2.48 years and height SDS of -3.88 ± 1.28 received rhGH for 6 months. IGF-I and IGFBP-3 were analyzed before and after 4 doses of rhGH. Results. The mean growth velocity (GV) before treatment was 5.28 ± 1.9 cm/year. GV increased after rhGH in five children to a mean GV of 10.3 ± 3.64 cm/year. Six children had normal basal IGF-I levels and two low levels. After 4 doses of rhGH, the IGF-I levels were normal in seven. There was no correlation between the growth response and the IGF-I generation test. Conclusions. Children with SRS have normal IGF-I generation test. There is no correlation between the generation test and the growth velocity after 6 months of rhGH.

Classificação das imunodeficiências congênitas: [revisão] / Classification of congenital immunodeficiencies: [review]

As imunodeficiências congênitas – ou primárias – apresentam elevada morbidade, podendo levar os pacientes à morte. O diagnóstico antenatal é relevante, podendo evitar complicações graves e irreversíveis, além de, habitualmente, contribuir para melhores prognósticos clínicos. A busca pela maximização do entendimento científico dessas condições mórbidas constitui uma grande ferramenta clínica para a compreensão, bem como desenvolvimento de novas modalidades de tratamento, capazes de auxiliar o sucesso de medidas clássicas e inovadoras (p. ex.: transplantes de células-tronco, recombinação gênica e outras), proporcionando, assim, maiores alternativas terapêuticas com promissores resultados para os pacientes.

Sangue de cordão umbilical para uso autólogo ou grupo de pacientes especiais: [revisão] / The potential therapeutic use of cord blood in autologous transplants or in special patients: a review and update

O sangue de cordão umbilical e placentário (SCUP) é uma rica fonte de células-tronco (CT) hematopoéticas e é amplamente utilizado como substituto da medula óssea em casos de transplante. As células do SCUP possuem vantagens sobre as células da medula óssea (MO), principalmente por serem mais jovens e apresentarem maior taxa proliferativa. Além dos progenitores hematopoéticos, o sangue de cordão umbilical contém progenitores endoteliais e mesenquimais, sugerindo sua possível aplicação nos novos protocolos de terapia celular para diferentes tecidos. Na presente revisão, discutimos a importância do armazenamento do sangue de cordão umbilical autólogo e as pesquisas desenvolvidas para a sua aplicação em doenças degenerativas.

Umbilical Cord Blood is a rich source of hematopoietic stem cells widely used as a substitute of bone marrow (BM) in transplants. Cells from umbilical cord blood present advantages over BM cells, mainly as they are younger and a have higher proliferative rate. Besides hematopoietic stem cells, umbilical cord blood contains endothelial and mesenchymal progenitor cells, suggesting their possible application in cell therapy protocols for different tissues. In this paper, we discuss the importance of autologous umbilical cord blood storage and the research on stem cell transplantation for degenerative diseases.

Novel mutations of the BSCL2 and AGPAT2 genes in 10 families with Berardinelli-Seip congenital generalized lipodystrophy syndrome.

CONTEXT: Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome, is a rare autosomal recessive disease caused by mutations in either the BSCL2 or AGPAT2 genes. This syndrome is characterized by an almost complete loss of adipose tissue usually diagnosed at birth or early infancy resulting in apparent muscle hypertrophy. Common clinical features are acanthosis nigricans, hepatomegaly with or without splenomegaly and high stature. Acromegaloid features, cardiomyopathy and mental retardation can also be present. DESIGN: We investigated 11 kindreds from different geographical areas of Brazil (northeast and southeast). All coding regions as well as flanking intronic regions of both genes were examined. Polymerase chain reaction (PCR) amplifications were performed using primers described previously and PCR products were sequenced directly. RESULTS: Four AGPAT2 and two BSCL2 families harboured the same set of mutations. BSCL2 gene mutations were found in the homozygous form in four kindreds (c.412C>T c.464T>C, c.518-519insA, IVS5-2A>G), and in two kindreds compound mutations were found (c.1363C>T, c.424A>G). In the other four families, one mutation of the AGPAT2 gene was found (IVS3-1G>C and c.299G>A). CONCLUSIONS: We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli-Seip syndrome and Brunzell syndrome (AGPAT2-related syndrome).

Progesterone and Estrogen Receptors in Neurofibromas of Patients with NF1.

Neurofibromatosis type 1 (NF1) or von Recklinghausen disease is a genetic disorder affecting the growth of cells in nervous system. One of the most remarkable characteristics of this disease is the development of benign tumors of the nervous system (neurofibromas).The purpose of this study was to test tissue samples taken from neurofibromas and plexiform neurofibromas of NF1 patients for the presence of estrogen and progesterone receptors. We used previously collected samples from patients registered in the database of the Centro Nacional de Neurofibromatose (CNNF-Brazil). Samples from twenty-five patients in the database presenting plexiform neurofibromas (N1 group) and 25 samples from the same database from patients presenting neurofibromas (N2 group) were tested.We observed positive staining for progesterone receptors in 13 of the neurofibroma samples and 19 of the plexiform neurofibroma samples. Among the neurofibroma samples, we observed one sample with positive estrogen receptor staining, but none of the plexiform neurofibroma samples showed positive staining. We suggest further studies to investigate in greater depth possible hormonal influences on the development and growth of neurofibromas and plexiform neurofibromas in NF1.

Single median maxillary central incisor: new data and mutation review.

BACKGROUND: Single median maxillary central incisor (SMMCI) is a rare anomaly that may occur alone or associated with other conditions, frequently as part of the holoprosencephaly (HPE) spectrum. However, it has been suggested that SMMCI alone, or associated with some midline defects, may be considered a different entity from HPE (OMIM: 147250). Families with SMMCI, without HPE cases, are difficult to counsel for the risk of HPE in future generations because the same midline defects described as part of the "SMMCI syndrome" can also be part of the HPE spectrum. METHODS: We screened five cases of SMMCI for mutations in three HPE genes, SHH, TGIF, and SIX3. RESULTS: A missense mutation c.686C>T was found in the gene SIX3 of one patient, which did not differ from the accepted 20% of known HPE gene mutations among all HPE cases. Our results and an extensive literature review of gene mutations in patients with SMMCI showed that 27/28 of them were in HPE genes: SHH (n = 21), SIX3 (n = 3), TGIF (n = 1), GLI2 (n = 1), and PTCH (n = 1), and only one in the SALL4 gene. CONCLUSIONS: The clinical findings in patients with SMMCI without HPE in families with mutations in HPE genes cannot be distinguished from the findings reported in the SMMCI syndrome. Therefore, persons with SMMCI and their relatives should be carefully investigated for related midline disorders, especially of the HPE spectrum, and all known HPE genes screened.

A clinical study of 77 patients with mucopolysaccharidosis type II.

AIM: This study aims to assess the clinical features of 77 South American patients (73 Brazilian) with mucopolysaccharidosis type II (MPS II). METHODS: Details of the patients and their disease manifestations were obtained from a review of medical records, interviews with the patients and/or their families, and physical examination of the patients. RESULTS: Mean birth weight was 3360 g, median age at onset of symptoms was 18 months and median age at diagnosis was 6 years. For the whole sample (median age, 8.2 years; range, 2.8-53.0 years), neurological degeneration, typical pebbly skin lesions, seizures and extensive dermal melanocytosis were found in 23.3, 13.0, 13.0 and 1.3% of the cases, respectively. The most frequently reported echocardiogram abnormality was mitral valve regurgitation. Refraction errors were the most common ophthalmological manifestation. The following characteristics were found to be associated with the severe form of MPS II: earlier age at biochemical diagnosis, higher levels of urinary glycosaminoglycans, language development delay, behavioural disturbances, poor school performance and mental retardation. CONCLUSION: Our results suggest that there is a considerable delay between the onset of signs and symptoms and the diagnosis of MPS II in Brazil (and probably in South America as well), and that many complications of this disease are underdiagnosed and undertreated. Therefore, the implementation of programmes aiming to increase the awareness of the disease, the availability of biochemical diagnostic tests and the provision of better support to affected patients is urgently needed.