Craniofacial care in Brazil : evaluation and suggestions to improve quality through the Unified Health System

Orientador: Vera Lucia Gil da Silva LopesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: As primeiras ações para inclusão da atenção a pessoas com anomalias craniofaciais (ACF) no Sistema Único de Saúde (SUS) ocorreram na década de 1990 e culminaram com a criação da Rede de Referência no Tratamento de Deformidades Craniofaciais (RRTDCF). Esta rede foi avaliada por Monlleó em 2004, momento em que foram identificados centros de atendimento a pessoas com ACF vinculados ao SUS, mas não à RRTDCF. Objetivos: (1) avaliar os centros de ACF não-RRTDCF; (2) discutir a política de atenção à saúde para ACF do Brasil; (3) elaborar cadastro dos centros estudados e (4) elaborar proposta de banco de dados de fendas orofaciais para o Brasil. Resultados: 82 centros de atendimento a pessoas com ACF participaram da avaliação. Estes centros estão concentrados no Sudeste e em universidades e compreendem serviços isolados, multiprofissionais e associações de pais. Apenas seis serviços multiprofissionais seguem critérios internacionais de composição de equipes. Nestes, odontólogos e cirurgiões são os especialistas mais freqüentes. Geneticistas clínicos estão envolvidos com aconselhamento genético em 35 serviços, enquanto em 30, outros profissionais realizam esta atividade. Sessenta e dois centros aderiram ao cadastro proposto. O banco de dados consiste em um projeto de registro clínico e familial de pessoas com fendas orofaciais atendidas em unidades da RRTDCF. Em torno deste, cinco projetos satélites foram elaborados: (1) banco de DNA; (2) avaliação da organização interna das unidades; (3) banco de profissionais de saúde e de protocolos de tratamento; (4) estudos de seguimento pós-cirúrgico, morbidade e mortalidade; (5) avaliação de satisfação dos usuários. Conclusões: os centros não-RRTDCF se sobrepõem à RRTDCF quanto à distribuição, procedimentos, clientela e financiamento. Iniqüidades, disparidades regionais e falta de integralidade permanecem como problemas. Acredita-se que a superação desses problemas requer a reformulação da política de atenção a pessoas com ACF e, para tanto, apresentam-se diretrizes. O cadastro de centros é uma ferramenta pública para minorar dificuldades de acesso a informações. Por sua vez, o banco de dados poderá fornecer subsídios para avaliação contínua dos serviços e para a reformulação da política de saúde para ACF no SUSAbstract: Health care for persons with craniofacial anomalies (CFA) officially started in Brazil in the nineties. It was consolidated through the Reference Network for Craniofacial Treatment (RRTDCF). The RRTDCF was evaluated by Monlleo in 2004 when several non-RRTDCF units operating in the Unified Health System (SUS) were identified. Aims: (1) to evaluate health care provided through non-RRTDCF units; (2) to inform the debate about craniofacial health care policy in Brazil; (3) to build up a record on CFA units; (4) to build up a Brazilian database on orofacial clefts. Results: 82 non-RRTDCF units took part of the survey. They are mainly located in the southeast, and in universities. They are funded by the government and comprise independent clinics, multiprofessional teams and parental associations. Only 6 multiprofessional units meet the international criteria for minimal CFA teams. Clinical geneticists are involved in genetic counselling in 35 units, however in 30 it is provided by untrained professionals. Sixty two units agreed to participate in the national record proposed. The Brazilian database on orofacial clefts was designed to record clinical and familial information on patients assisted through the RRTDCF. Additionally, five satellite projects were built: (1) biobank of DNA; (2) general care assessment; (3) database of healthcare professionals and assessment of treatment protocols; (4) follow-up studies on surgical treatment and morbidity/mortality and (5) patient/parent satisfaction studies. Conclusion: non-RRTDCF units overlap RRTDCF regarding distribution, treatment provided, type of CFA treated, and funding. The current system does not ensure equity and coordination of care, and keeps up regional disparities. It is believed that these problems may be overcome through changes in the current national health policy for CFA in Brazil and suggestions are given in this regard. The national record on CFA units is a tool in the public interest and can improve equity of access to services. The database, on the other hand, is an achievable strategy to set up appraisal and audit systems and to support the reformulation of health policy for persons with CFA in the SUSDoutoradoGenetica MedicaDoutor em Ciências Médica

Anomalias craniofaciais, genetica e saude publica : contribuições para o reconhecimento da situação atual da assistencia no Sistema Unico de Saude

Orientador: Vera Lucia Gil da Silva LopesDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: As anomalias craniofaciais estão entre os defeitos congênitos humanos mais freqüentes e demandam assistência multiprofissional, integral e especializada, cujo custo é elevado. O médico geneticista destaca-se na equipe por ter habilidades para a caracterização etiológica e nosológica dessas condições, fundamentais para o aconselhamento genético e a correta obtenção de dados epidemiológicos. Todavia, o acesso ao tratamento ainda é precário em muitas nações, motivo pelo qual a Organização Mundial de Saúde vem estimulando pesquisas sobre oferta de serviços e qualidade da assistência prestada. Além disso, é reconhecido que a ampla variação da qualidade e dos custos da assistência estão relacionados às características estruturais e funcionais dos serviços. A primeira iniciativa para atenção a portadores de Anomalias Craniofaciais no Sistema Único de Saúde do Brasil ocorreu em 1993. Com a criação da Rede de Referência no Tratamento de Deformidades Craniofaciais, o atendimento foi ampliado, contando atualmente com 29 centros credenciados. Até o momento, esses centros não foram caracterizados. Os objetivos deste trabalho foram avaliar a organização dessa Rede, descrever a estrutura e funcionamento dos centros que a integram e verificar a oferta e o acesso à genética clínica nesses locais. Para coleta dos dados, foi utilizado um questionário semi-estruturado, remetido por correio. Os resultados demonstram agregação de centros no Sudeste, em universidades e na área de fissuras labiopalatais, com atendimento de rotina em cerca de 90% deles. A denominação da rede de assistência não parece corresponder à sua atual abrangência. As equipes estão constituídas de acordo com critérios americanos em 14 e, com europeus, em cinco centros participantes do estudo. Há geneticistas clínicos em 13 centros. Dentre esses, 61,8% contam com apenas um especialista dessa área. Apesar da baixa inserção do geneticista, em 22 centros, pais e pacientes solicitam informações sobre etiologia e prevenção que são fornecidas em 80,0% dos centros; todavia em 55% deles essa atividade é realizada por médicos não geneticistas e outros integrantes da equipe. Em conclusão, os dados sugerem a necessidade de revisão da definição, objetivos, abrangência e critérios de credenciamento dos centros de atendimento e caracterizam a precariedade da oferta e do acesso à genética clínica na Rede de Referência no Tratamento de Deformidades CraniofaciaisAbstract: Craniofacial anomalies are one of the most common birth defects in man, which have considerable medical costs in view of the long, specialized and complex treatment. The presence of the Clinical Geneticist on the team is important for clinical and etiologic characterization of these anomalies, genetic counseling and epidemiologic register. As the access for treatment is not easy in many countries, the World Health Organization launched a project for research availability and quality of the specialized services. Previous research demonstrates that variation of costs and quality of the services were related with theirs structural and functional characteristics, as well. The first initiative for public craniofacial anomalies health care in Brazil was in 1993. An important improvement occurred with the creation of the Net for Craniofacial Deformities Treatment, which is composed by 29 centers. Until now, these centers had not been studied before. The aims of this study were to evaluate the Net for Craniofacial Deformities Treatment, to describe the structural and functional characteristics of these centers and the access for genetic evaluation and genetic counseling for individuals and families in them. Data were collected by a questionnaire mailed for all these centers. The results showed an increased of centers in Southeast and in universities. Cleft lip and palate is the main clinical condition treated. Routine attendance occurred in 90% of the centers. Teams¿ composition is similar to American criteria in 14 of the centers and to European, in 5. The denomination of this assistance net does not seem in accordance to its actual activities. Clinical geneticist was present in 13 centers and 61,8% had one professional. In spite of few Clinical Geneticists in the composition of the teams, in 22 centers of attendance patients and parents asked for etiology and prevention, which have been done in 80% of them. These informations are transmitted by a non-specialized physicians and others members of the team in 55% of the centers. These data suggested that it would be necessary the revision of definition, goals, activities and standards for inclusion of the craniofacial centers. They also demonstrated that the availability and the access for clinical geneticist is not enough in the Net for Craniofacial Deformities Treatment of BrazilMestradoGenetica MedicaMestre em Ciências Médica

Investigation of genetic factors underlying typical orofacial clefts: mutational screening and copy number variation

Typical orofacial clefts (OFCs) comprise cleft lip, cleft palate and cleft lip and palate. The complex etiology has been postulated to involve chromosome rearrangements, gene mutations and environmental factors. A group of genes including IRF6, FOXE1, GLI2, MSX2, SKI, SATB2, MSX1 and FGF has been implicated in the etiology of OFCs. Recently, the role of the copy number variations (CNVs) has been studied in genetic defects and diseases. CNVs act by modifying gene expression, disrupting gene sequence or altering gene dosage. The aims of this study were to screen the above-mentioned genes and to investigate CNVs in patients with OFCs. The sample was composed of 23 unrelated individuals who were grouped according to phenotype (associated with other anomalies or isolated) and familial recurrence. New sequence variants in GLI2, MSX1 and FGF8 were detected in patients, but not in their parents, as well as in 200 control chromosomes, indicating that these were rare variants. CNV screening identified new genes that can influence OFC pathogenesis, particularly highlighting TCEB3 and KIF7, that could be further analyzed. The findings of the present study suggest that the mechanism underlying CNV associated with sequence variants may play a role in the etiology of OFC.Typical orofacial clefts (OFCs) comprise cleft lip, cleft palate and cleft lip and palate. The complex etiology has been postulated to involve chromosome rearrangements, gene mutations and environmental factors. A group of genes including IRF6, FOXE1, GLI6011725FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2008/10596-0304455/2012-

Evaluation of Craniofacial Care Outside the Brazilian Reference Network for Craniofacial Treatment

Objective: To describe health care provided outside the Brazilian Reference Network for Craniofacial Treatment, and to inform the debate about craniofacial health care policy in Brazil. Design: Observational, retrospective cohort. Methods: Craniofacial care providers completed the same questionnaire previously used to evaluate the Brazilian Reference Network for Craniofacial Treatment (RRTDCF). Results: Units outside the RRTDCF are mainly located in the southeast region of Brazil and in universities. They comprise 56 independent clinics, 22 combined clinics, and four parental associations. Services provided are variable from unit to unit and just six of them meet the American Cleft Palate-Craniofacial Association minimum team standard. Genetic evaluation and counseling is provided by clinical geneticists in 35 units; whereas, in 30 units, it is undertaken by untrained professionals. Conclusion: A significant number of craniofacial units work in parallel and overlap the RRTDCF. They are funded by the government but not recognized as craniofacial teams. Regional disparities and lack of coordination within and between cleft lip and/or cleft palate (CL/P) teams are unsolved problems. Non-RRTDCF units are heterogeneous concerning configuration, service provided, areas of treatment, and composition of the teams. A nationwide and voluntary database on orofacial clefts is a proposed strategy to address some of these problems. Anticipated benefits include strengthening the collaboration within and between healthcare teams and supplying health authorities with a comprehensive and population-specific source of information on this prevalent and potentially preventable group of birth defects.46220421

Similar interstitial deletions of the KAL-1 gene in two Brazilian families with X-linked Kallmann Syndrome

Mutations in the KAL-1 gene localized at Xp22.3 have been shown to be responsible for the X-linked Kallmann syndrome (KS), a disorder characterized by the association of hypogonadotropic hypogonadism and anosmia. In this paper, we describe the investigation of two families with X-linked KS, in which similar interstitial deletions ning exons 5 to 10 of the KAL-1 gene were identified. The presence of interspersed repetitive DNA sequences within the KAL-1 gene might have predisposed to this type of mutation

Genomic Investigation of Balanced Chromosomal Rearrangements in Patients with Abnormal Phenotypes

International audienceBalanced chromosomal rearrangements (BCR) are associated with abnormal phenotypes in approximately 6% of balanced translocations and 9.4% of balanced inversions. Abnormal phenotypes can be caused by disruption of genes at the breakpoints, deletions, or positional effects. Conventional cytogenetic techniques have a limited resolution and do not enable a thorough genetic investigation. Molecular techniques applied to BCR carriers can contribute to the characterization of this type of chromosomal rearrangement and to the phenotype-genotype correlation. Fifteen individuals among 35 with abnormal phenotypes and BCR were selected for further investigation by molecular techniques. Chromosomal rearrangements involved 11 reciprocal translocations, 3 inversions, and 1 balanced insertion. Array genomic hybridization (AGH) was performed and genomic imbalances were detected in 20% of the cases, 1 at a rearrangement breakpoint and 2 further breakpoints in other chromosomes. Alterations were further confirmed by FISH and associated with the phenotype of the carriers. In the analyzed cases not showing genomic imbalances by AGH, next-generation sequencing (NGS), using whole genome libraries, prepared following the Illumina TruSeq DNA PCR-Free protocol (Illumina®) and then sequenced on an Illumina HiSEQ 2000 as 150-bp paired-end reads, was done. The NGS results suggested breakpoints in 7 cases that were similar or near those estimated by karyotyping. The genes overlapping 6 breakpoint regions were analyzed. Follow-up of BCR carriers would improve the knowledge about these chromosomal rearrangements and their consequences