Gomez-López-Hernández syndrome: A case report with clinical and molecular evaluation and literature review.

Gomez-López-Hernández syndrome (GLHS) is characterized by rhombencephalosynapsis (RES), alopecia, trigeminal anesthesia and a distinctive phenotype, including brachyturricephaly. It has been suggested that GLHS should be considered as part of the spectrum of RES-associated conditions that include alopecia, trigeminal anesthesia, and craniofacial anomalies, rather than a distinct entity. To the best of our knowledge, 57 patients with GLHS have been described. Despite its first description in 1979, the etiology of this syndrome remains unknown. Here, we describe, to our knowledge, the first case of a patient with GLHS who was molecularly evaluated and had been prenatally exposed to misoprostol. We also reviewed the clinical and morphological features of the patients described to date to better delineate the phenotype and focus on any evidence for adverse pregnancy outcomes or exposure, including teratogens.

Association between genetic polymorphisms and osteoarthritis development. Overview of systematic reviews.

OBJECTIVE: To identify, critically evaluate and synthesize the evidence obtained from systematic reviews on the association between genetic polymorphisms and osteoarthritis (OA) development. METHODS: Considering gene polymorphisms associated with OA susceptibility (risk or protection), a comprehensive search was conducted in the following databases, without date or language restrictions: MEDLINE, via Pubmed; Embase, via Elsevier; Cochrane Database of Systematic Reviews, via Wiley; Biblioteca Virtual em Saúde. Gray literature was also searched through the OpenGrey database. The AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews) was used to assess the methodological quality of the included systematic reviews. RESULTS: We included 14 systematic reviews of case-control studies comparing individuals with a radiographic diagnosis of all OA types and healthy controls, all submitted to the genetic examination of different polymorphisms in candidate genes. Meta-analyses showed a protective effect against knee and hand OA associated with GDF-5 gene (odds ratio [OR] 0.90, 95% confidence interval (CI) 0.85-0.95), and knee OA with ESRα gene (OR 0.63, 95% CI 1.26-1.97). SMAD3 gene was associated with knee and hip OA risk (OR 1.21. 95% CI 1.07-1.38) and MMP-1 gene was associated with temporomandibular OA (OR 1.58. 95% CI 1.26-1.97). CONCLUSION: Based on low-quality to critically-low-quality systematic reviews, some gene polymorphisms seem to be associated with risk or protection for OA. Further high-quality studies are needed to validate these hypotheses, contribute to disease understanding, and possibly help the decision-making related to early diagnosis and treatment options for OA. PROSPERO register CRD42021234231.

A novel variant in the COX15 gene causing a fatal infantile cardioencephalomyopathy: A case report with clinical and molecular review.

The cytochrome c-oxidase (COX) enzyme, also known as mitochondrial complex IV (MT-C4D), is a transmembrane protein complex found in mitochondria. COX deficiency is one of the most frequent causes of electron transport chain defects in humans. Therefore, high energy demand organs and tissues are affected in patients with mutations in the COX15 gene, with variable phenotypic expressiveness. We describe the case of a male newborn with hypertrophic cardiomyopathy and serum and cerebrospinal fluid hyperlacticaemia, whose exome sequencing revealed two variants in a compound heterozygous state: c.232G > A; p.(Gly78Arg), classified as likely pathogenic, and c.452C > G; p.(Ser151Ter), as pathogenic; the former never previously described in the literature.

Investigating 22q11.2 deletion and other chromosomal aberrations in fetuses with heart defects detected by prenatal echocardiography.

Congenital heart disease (CHD) is the most common birth defect and the leading cause of mortality in the first year of life. In fetuses with a heart defect, chromosomal abnormalities are very frequent. Besides aneuploidy, 22q11.2 deletion is one of the most recognizable chromosomal abnormalities causing CHD. The frequency of this abnormality varies in nonselected populations. This study aimed to investigate the incidence of the 22q11.2 deletion and other chromosomal alterations in a Brazilian sample of fetuses with structural cardiac anomalies detected by fetal echocardiography. In a prospective study, 68 fetuses with a heart defect were evaluated. Prenatal detection of cardiac abnormalities led to identification of aneuploidy or structural chromosomal anomaly in 35.3% of these cases. None of the fetuses with apparently normal karyotypes had a 22q11.2 deletion. The heart defects most frequently associated with chromosomal abnormalities were atrioventricular septal defect (AVSD), ventricular septal defect (VSD), and tetralogy of Fallot. Autosomal trisomies 18 and 21 were the most common chromosomal abnormalities. The study results support the strong association of chromosome alterations and cardiac malformation, especially in AVSD and VSD, for which a chromosome investigation is indicated. In fetuses with an isolated conotruncal cardiopathy, fluorescence in situ hybridization (FISH) to investigate a 22q11.2 deletion is not indicated.

Complex toe syndactyly with characteristic facial phenotype: a new syndrome?

Nonsyndromic syndactyly is a common, heterogeneous hereditary condition of webbed fingers and toes that can be cutaneous or bony, unilateral or bilateral. We describe a patient with complex toe syndactyly and oligodactyly, some interesting skeletal hand findings and atypical facial features without other case like this described before. Cenani-Lenz syndrome (CLS) is a rare disorder with total syndactyly and irregular synostosis of carpal, metacarpal and phalanges, it may involve ulna and radius and digital rays may be absent, some of these were described with atypical facial features and one patient had renal hypoplasia and vertebral anomalies but our patient does not have the oligodactyly or syndactyly of the hands that is consistently present in all patients with CLS. The atypical facial features of our patient resemble Kabuki syndrome but oligodactyly and complex syndactyly have not been described in Kabuki syndrome and this patient has normal intelligence, and extreme eyelid defect (resembling ablepharon). Therefore, for our patient, we suggested to treat in a new condition of limb anomalies and atypical face.

[Congenital Anomalies Detected at Birth in Newborns of Adolescent Women]. / Anomalias Congénitas Identificadas ao Nascimento em Recém-Nascidos de Mulheres Adolescentes.

INTRODUCTION: To analyze the prevalence of congenital anomalies detected at birth among children of pregnant adolescents, emphasizing the most common types and the time of diagnosis. MATERIAL AND METHODS: Retrospective study of type census, in which were analyzed in all newborns, living or dead, weighing more than 500 g of women who gave birth at Hospital São Paulo in a period of six years. The fetuses bearing anomalies were identified prenatally or through postnatal physical examination period, according to the criteria of the Latin American Collaborative Study of Congenital Malformations. The results were expressed descriptively using absolute and relative values, the prevalence of anomalies was calculated, as well as the comparison between groups using nonparametric tests. RESULTS: We analyzed 6 257 pregnancies, of which 577 newborns had some congenital anomaly identified at birth (prevalence 9.2%). Among these 6 257, 907 were adolescents, which showed a 9.9% prevalence of anomalies among their newborns. There was no significant difference between the presence of abnormalities in newborns of adolescents and women with age greater than or equal to 20 years. About 56% of congenital anomalies were diagnosed in the prenatal period. We observed a higher prevalence of defects of neural tube between newborns of adolescents (p = 0.027). DISCUSSION: We observed high rate of deliveries in adolescents, higher than developed countries. We observed also high frequency of congenital anomalies in newborns, probably because our tertiary reference center. The high prevalence of neural tube defect among young pregnant women could be explained by the absent of acid folic supplementation in non-planned gestations which is typical of adolescents. CONCLUSION: The prevalence and time of diagnosis of congenital anomalies showed similar behavior among newborns of teenagers and women with age greater than or equal to 20 years, except for the defects of the neural tube, which were more prevalent among newborns of teenagers.

Introdução: Analisar a prevalência das anomalias congénitas, detetadas no nascimento, entre filhos de gestantes adolescentes, enfatizando os tipos mais comuns e a época do diagnóstico. Material e Métodos: Estudo retrospetivo do tipo censo, no qual foram analisados todos recém-nascidos, vivos ou mortos, com peso superior a 500 g, de mulheres que tiveram o parto no Hospital São Paulo num período de seis anos. Os produtos da conceção portadores de anomalias foram identificados no período pré-natal ou através do exame físico pós-natal, segundo os critérios do Estudo Colaborativo Latino-Americano das Malformações Congênitas. Os resultados são apresentados de forma descritiva através de valores absolutos e relativos, calcula-se a prevalência das anomalias e comparam-se os diferentes grupos recorrendo a testes não paramétricos. Resultados: Foram analisadas 6 257 gestações, das quais 577 resultaram em recém-nascidos com alguma anomalia congénita identificada no nascimento (prevalência de 9,2%). Do total de gestações, 907 eram de adolescentes (idade inferior a 20 anos), para as quais se verificou uma prevalência de anomalias nos recém-nascidos de 9,9%. Comparando os recém-nascidos de adolescentes com os das mulheres com idade superior a 20 anos, apenas se encontrou diferença estatisticamente significativa para a prevalência dos defeitos do tubo neural (p = 0,027). Discussão: Observamos uma alta taxa de partos em adolescentes, acima das taxas dos países desenvolvidos. Observamos também alta frequência de anomalias congénitas em recém-nascidos, provavelmente por sermos um serviço terciário de referência. A elevada prevalência dos defeitos do tubo neural entre grávidas jovens pode ser explicada pela não suplementação pré-concecional de ácido fólico em gravidezes não planeadas, como é característico nas adolescentes.Conclusão: A prevalência e momento do diagnóstico das anomalias congénitas em recém-nascidos apresentam comportamentos semelhantes entre grávidas com idade inferior ou superior a 20 anos, exceto para os defeitos do tubo neural, de maior prevalência nos recém-nascidos das grávidas adolescentes.

[Use of the Internet to report congenital malformations on birth certificates at four public maternity hospitals in the city of São Paulo, Brazil]. / A utilização da Internet na notificação dos defeitos congênitos na Declaração de Nascido Vivo em quatro maternidades públicas do Município de São Paulo, Brasil.

The aim of this study was to improve the completion of item 34 on birth certificates at four maternity hospitals in the city of São Paulo, Brazil, in the year 2008. The database of the Municipal Health Department's Information System on Live Births was used to monitor trends in reporting birth defects. An electronic web-based medical record was used to refer indeterminate cases to a leading medical genetics referral center. The electronic medical record contained the patient history, physical examination, and photographs of the newborn. Four maternity hospitals were assessed, with a total of 10,000 births during the year. None of the four hospitals had a staff geneticist. According to the Information System on Live Births, there was an increase in the number of birth defects reported by the four maternity hospitals when compared to previous years and to records for the city of São Paulo as a whole. Based on the findings, the web-based referral and counter-referral method proved efficient.

A utilização da Internet na notificacao dos defeitos congenitos na Declaracao de Nascido Vivo em quatro maternidades publicas do municipio de Sao Paulo, Brasil / Use of the Internet to report congenital malformations on birth certificates at four public maternity hospitals in the city of Sao Paulo, Brazil

O objetivo foi aumentar a frequencia da notificacao de anomalias congenitas no campo 34 da Declaracao de Nascido Vivo em quatro maternidades do Municipio de Sao Paulo, Brasil, ao longo do ano de 2008. Utilizamos o banco de dados do Sistema de Informacoes sobre Nascidos Vivos da Secretaria Municipal de Saude de Sao Paulo para acompanhar a evolucao dos registros dos defeitos congenitos. Mediante prontuario eletronico, via Internet, os casos suspeitos eram enviados para um centro de referencia em genetica medica. O prontuario eletronico contem anamnese, exame fisico e fotos do recem-nascido. O estudo ocorreu em quatro maternidades com uma amostra total de 10 mil nascimentos no ano e que nao apresentam medico geneticista. Houve aumento da notificacao dos defeitos congenitos nas quatro maternidades onde o estudo foi realizado quando comparado com os anos anteriores e com o registro do Municipio de Sao Paulo. O metodo de referencia e contra-referencia utilizando a Internet mostrou-se eficaz.

The aim of this study was to improve the completion of item 34 on birth certificates at four maternity hospitals in the city of Sao Paulo, Brazil, in the year 2008. The database of the Municipal Health Department's Information System on Live Births was used to monitor trends in reporting birth defects. An electronic web-based medical record was used to refer indeterminate cases to a leading medical genetics referral center. The electronic medical record contained the patient history, physical examination, and photographs of the newborn. Four maternity hospitals were assessed, with a total of 10,000 births during the year. None of the four hospitals had a staff geneticist. According to the Information System on Live Births, there was an increase in the number of birth defects reported by the four maternity hospitals when compared to previous years and to records for the city of Sao Paulo as a whole. Based on the findings, the web-based referral and counter-referral method proved efficient.

Clinical, genetical, radiological, and anatomopathological survey of 17 patients with lethal osteochondrodysplasias

Foram avaliados 17 pacientes com suspeita diagnóstica de osteocondrodisplasias letais. O diagnóstico definitivo foi estabelecido através da avaliaçäo clínica, estudo radiológico e pela necropsia. Foi também procedido o aconselhamento genético aos familiares dos afetados. Houve confirmaçäo diagnóstica específica em 16 casos. Em todos, o diagnóstico nosológico foi clinicamente suspeitado. O método mais eficiente para determinaçäo diagnóstica foi, contudo, o estudo radiológico do esqueleto. Isto corrobora a orientaçäo da Classificaçäo Internacional das Osteocondrodisplasias (International Working Group on Constitutional Disease of Bone, 1992) ao adotar o critério radiológico como o mais relevante na classificaçäo deste grupo sindrômico. O estudo anatomopatológico, além de detectar anomalias internas, foi eficiente, através do estudo do fragmento ósseo, identificando alteraçöes na placa epifisária de crescimento, porém com baixa especificidade, na maioria das vezes. Este método, por outro lado, foi decisivo na diferenciaçäo diagnóstica de dois casos.

Osteogênese imperfeita-forma letal: estudo genético clínico, radiológico e anatomopatológico de três casos / Imperfecta osteogenesis - lethal form: Clinical genetic, radiologic estudy

Apresentamos três casos de Osteogênese imperfeita tipo II (forma letal). A investigaçäo foi realizada pela descriçäo fenotípica, antropometria, estudo radiológico e necropsia. Foram selecionados de uma amostra de casos de osteocondrodisplasias letais. Dois dos casos apresentavam a forma IIA da osteogênese Imperfeita enquanto que o último caso, IIB. A sistematizaçäo diagnóstico é fundamental pois trata-se de patologia heterogênea do ponto de vista genético. Assim, o diagnóstico preciso dos subtipos é fundamental para o aconselhamento genético