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Papers by Rita Maria Alves

Research paper thumbnail of Perfil epidemiológico de anomalias congênitas no estado da Bahia

Revista de Ciências Médicas e Biológicas, 2018

Vivos-SINASC, e Estatísticas Vitais do TABNET disponibilizados nesta plataforma. Resultados: Foi ... more Vivos-SINASC, e Estatísticas Vitais do TABNET disponibilizados nesta plataforma. Resultados: Foi observado um total de 7406 nascidos vivos por ocorrência de anomalias congênitas neste período, onde o maior número de casos foi registrado em 2016 (23,95%). A média de nascidos vivos com anomalias congênitas corresponde 2.468 indivíduos. As os defeitos congênitos de maior incidência se referem a malformações e deformidades congênitas do aparelho osteomuscular (48,04%). As alterações congênitas que registraram maior morbidade estavam relacionadas àquelas originadas do aparelho circulatório (26,75% de todos os casos de internação), sendo também as principais causas de óbito neste mesmo período (38,07%).Conclusão: Nesta série histórica observa-se que as anomalias são as mais frequentes em nascidos vivos no período de 2012 a 2016, onde malformações congênitas do aparelho circulatório as de maior causa de morbidade e mortalidade no primeiro ano de vida. Um número de 1060 óbitos por malformações cardíacas e circulatórias em menores de 1 ano de vida foi registrado a despeito de um total de nascidos vivos de 161 indivíduos registrados nessa base de dados. Acreditamos que a divergência dessas informações possa ter ocorrido por falha na alimentação dos dados, pela forma da implantação do e pelas dificuldades quanto à interpretação e o uso do CID-10. A alimentação inadequada das informações pelo DATASUS limita a representação real dos valores para se construir um mapeamento do comportamento das malformações congênitas e suas repercussões em saúde pública.

Research paper thumbnail of Epidemiological and clinical suspicion of congenital Zika virus infection: Serological findings in mothers and children from Brazil

Journal of Medical Virology, 2019

The emergence of Zika virus in the Americas has caused an increase of babies born with microcepha... more The emergence of Zika virus in the Americas has caused an increase of babies born with microcephaly or other neurological malformations. The differential diagnosis of Zika infection, particularly serological diagnosis, is an important but complex issue. In this study, we describe clinical manifestations of 94 suspected cases of congenital Zika from Bahia state, Brazil, and the results of serological tests performed on children and/or their mothers at an average of 71 days after birth. Anti-Zika immunoglobulin M (IgM) antibodies were detected in 44.4% and in 7.1% of samples from mothers and children, respectively. Nearly all the IgM, and 92% of immunoglobulin G positive results were confirmed by neutralization test. Zika specific neutralizing antibodies were detected in as much as 90.4% of the cases. Moreover, dengue specific neutralizing antibodies were detected in 79.0% of Zika seropositive mothers. In conclusion, Zika IgM negative results should be considered with caution, due to a possible rapid loss of sensitivity after birth, while the NS1-based Zika IgM enzyme-linked immunosorbent assay test we have used has demonstrated to be highly specific. In a high percentage of cases, Zika specific neutralizing antibodies were detected, which are indicative of a past Zika infection, probably occurred during pregnancy in this population.

Research paper thumbnail of Novel ANKRD11 gene mutation in an individual with a mild phenotype of KBG syndrome associated to a GEFS+ phenotypic spectrum: a case report

BMC Medical Genetics, 2019

Background: KBG syndrome is a very rare autosomal dominant disorder, characterized by macrodontia... more Background: KBG syndrome is a very rare autosomal dominant disorder, characterized by macrodontia, distinctive craniofacial findings, skeletal findings, post-natal short stature, and developmental delays, sometimes associated with seizures and EEG abnormalities. So far, there have been over 100 cases of KBG syndrome reported. Case presentation: Here, we describe two sisters of a non-consanguineous family, both presenting generalized epilepsy with febrile seizures (GEFS+), and one with a more complex phenotype associated with mild intellectual disability, skeletal and dental anomalies. Whole exome sequencing (WES) analysis in all the family members revealed a heterozygous SCN9A mutation, p.(Lys655Arg), shared among the father and the two probands, and a novel de novo loss of function mutation in the ANKRD11 gene, p.(Tyr1715*), in the proband with the more complex phenotype. The reassessment of the phenotypic features confirmed that the patient fulfilled the proposed diagnostic criteria for KBG syndrome, although complicated by early-onset isolated febrile seizures. EEG abnormalities with or without seizures have been reported previously in some KBG cases. The shared variant, occurring in SCN9A, has been previously found in several individuals with GEFS+ and Dravet syndrome. Conclusions: This report describe a novel de novo variant in ANKRD11 causing a mild phenotype of KGB syndrome and further supports the association of monogenic pattern of SCN9A mutations with GEFS+. Our data expand the allelic spectrum of ANKRD11 mutations, providing the first Brazilian case of KBG syndrome. Furthermore, this study offers an example of how WES has been instrumental allowing us to better dissect the clinical phenotype under study, which is a multilocus variation aggregating in one proband, rather than a phenotypic expansion associated with a single genomic locus, underscoring the role of multiple rare variants at different loci in the etiology of clinical phenotypes making problematic the diagnostic path. The successful identification of the causal variant in a gene may not be sufficient, making it necessary to identify other variants that fully explain the clinical picture. The prevalence of blended phenotypes from multiple monogenic disorders is currently unknown and will require a systematic re-analysis of large WES datasets for proper diagnosis in daily practice.

Research paper thumbnail of Perfil epidemiológico de anomalias congênitas no estado da Bahia

Revista de Ciências Médicas e Biológicas, 2018

Vivos-SINASC, e Estatísticas Vitais do TABNET disponibilizados nesta plataforma. Resultados: Foi ... more Vivos-SINASC, e Estatísticas Vitais do TABNET disponibilizados nesta plataforma. Resultados: Foi observado um total de 7406 nascidos vivos por ocorrência de anomalias congênitas neste período, onde o maior número de casos foi registrado em 2016 (23,95%). A média de nascidos vivos com anomalias congênitas corresponde 2.468 indivíduos. As os defeitos congênitos de maior incidência se referem a malformações e deformidades congênitas do aparelho osteomuscular (48,04%). As alterações congênitas que registraram maior morbidade estavam relacionadas àquelas originadas do aparelho circulatório (26,75% de todos os casos de internação), sendo também as principais causas de óbito neste mesmo período (38,07%).Conclusão: Nesta série histórica observa-se que as anomalias são as mais frequentes em nascidos vivos no período de 2012 a 2016, onde malformações congênitas do aparelho circulatório as de maior causa de morbidade e mortalidade no primeiro ano de vida. Um número de 1060 óbitos por malformações cardíacas e circulatórias em menores de 1 ano de vida foi registrado a despeito de um total de nascidos vivos de 161 indivíduos registrados nessa base de dados. Acreditamos que a divergência dessas informações possa ter ocorrido por falha na alimentação dos dados, pela forma da implantação do e pelas dificuldades quanto à interpretação e o uso do CID-10. A alimentação inadequada das informações pelo DATASUS limita a representação real dos valores para se construir um mapeamento do comportamento das malformações congênitas e suas repercussões em saúde pública.

Research paper thumbnail of Epidemiological and clinical suspicion of congenital Zika virus infection: Serological findings in mothers and children from Brazil

Journal of Medical Virology, 2019

The emergence of Zika virus in the Americas has caused an increase of babies born with microcepha... more The emergence of Zika virus in the Americas has caused an increase of babies born with microcephaly or other neurological malformations. The differential diagnosis of Zika infection, particularly serological diagnosis, is an important but complex issue. In this study, we describe clinical manifestations of 94 suspected cases of congenital Zika from Bahia state, Brazil, and the results of serological tests performed on children and/or their mothers at an average of 71 days after birth. Anti-Zika immunoglobulin M (IgM) antibodies were detected in 44.4% and in 7.1% of samples from mothers and children, respectively. Nearly all the IgM, and 92% of immunoglobulin G positive results were confirmed by neutralization test. Zika specific neutralizing antibodies were detected in as much as 90.4% of the cases. Moreover, dengue specific neutralizing antibodies were detected in 79.0% of Zika seropositive mothers. In conclusion, Zika IgM negative results should be considered with caution, due to a possible rapid loss of sensitivity after birth, while the NS1-based Zika IgM enzyme-linked immunosorbent assay test we have used has demonstrated to be highly specific. In a high percentage of cases, Zika specific neutralizing antibodies were detected, which are indicative of a past Zika infection, probably occurred during pregnancy in this population.

Research paper thumbnail of Novel ANKRD11 gene mutation in an individual with a mild phenotype of KBG syndrome associated to a GEFS+ phenotypic spectrum: a case report

BMC Medical Genetics, 2019

Background: KBG syndrome is a very rare autosomal dominant disorder, characterized by macrodontia... more Background: KBG syndrome is a very rare autosomal dominant disorder, characterized by macrodontia, distinctive craniofacial findings, skeletal findings, post-natal short stature, and developmental delays, sometimes associated with seizures and EEG abnormalities. So far, there have been over 100 cases of KBG syndrome reported. Case presentation: Here, we describe two sisters of a non-consanguineous family, both presenting generalized epilepsy with febrile seizures (GEFS+), and one with a more complex phenotype associated with mild intellectual disability, skeletal and dental anomalies. Whole exome sequencing (WES) analysis in all the family members revealed a heterozygous SCN9A mutation, p.(Lys655Arg), shared among the father and the two probands, and a novel de novo loss of function mutation in the ANKRD11 gene, p.(Tyr1715*), in the proband with the more complex phenotype. The reassessment of the phenotypic features confirmed that the patient fulfilled the proposed diagnostic criteria for KBG syndrome, although complicated by early-onset isolated febrile seizures. EEG abnormalities with or without seizures have been reported previously in some KBG cases. The shared variant, occurring in SCN9A, has been previously found in several individuals with GEFS+ and Dravet syndrome. Conclusions: This report describe a novel de novo variant in ANKRD11 causing a mild phenotype of KGB syndrome and further supports the association of monogenic pattern of SCN9A mutations with GEFS+. Our data expand the allelic spectrum of ANKRD11 mutations, providing the first Brazilian case of KBG syndrome. Furthermore, this study offers an example of how WES has been instrumental allowing us to better dissect the clinical phenotype under study, which is a multilocus variation aggregating in one proband, rather than a phenotypic expansion associated with a single genomic locus, underscoring the role of multiple rare variants at different loci in the etiology of clinical phenotypes making problematic the diagnostic path. The successful identification of the causal variant in a gene may not be sufficient, making it necessary to identify other variants that fully explain the clinical picture. The prevalence of blended phenotypes from multiple monogenic disorders is currently unknown and will require a systematic re-analysis of large WES datasets for proper diagnosis in daily practice.