Turner syndrome and neuropsychological abnormalities: a review and case series / Síndrome de Turner e alterações neuropsicológicas: uma revisão e série de casos

ABSTRACT Objective: The objective of this study was to establish the genotype-phenotype correlation between karyotype results and the neurological and psychiatric alterations presented in patients with Turner syndrome (TS). Methods: A retrospective study was conducted on the medical records of 10/140 patients with TS and neurophysiological abnormalities seen at a university hospital in southern Brazil. In addition, a literature review spanning the period from January 1, 2012 to January 1, 2023 was carried out using the PubMed and Virtual Health Library databases. Results: Our study showed a potential correlation between neurological and psychiatric alterations in patients with TS. These findings are in accordance with those described in literature such as a high prevalence of learning or intellectual disabilities. However, our sample found more seizure episodes than those reported in other studies. Conclusions: The correlation established could be due to X chromosome dose-effect, as the review suggests that sex chromosome number and hormonal development can be associated with verbal, social, and cognitive skills or impairments.

RESUMO Objetivo: O objetivo deste estudo foi realizar a correlação genótipo-fenótipo entre os resultados de cariótipos e as alterações neurológicas e psiquiátricas apresentadas em pacientes com síndrome de Turner (ST). Métodos: Um estudo retrospectivo foi conduzido nos registros médicos de 10/140 pacientes com ST e deficiências neuropsicológicas atendidos pelo Serviço de Genética Clínica de um hospital do sul do Brasil. Ademais, uma revisão foi realizada pelas plataformas científicas PubMed e Biblioteca Virtual em Saúde (BVS) de artigos publicados entre 1o de janeiro de 2012 e 1o de janeiro de 2023. Foram selecionados 14 artigos em uma análise em duas etapas. Resultados: Nossa pesquisa mostrou potencial correlação entre alterações neurológicas e psiquiátricas em pacientes com ST. Esses achados corroboram os descritos por outros autores — como a elevada prevalência de dificuldades de aprendizagem ou intelectuais. Entretanto, nossa amostra encontrou mais episódios convulsivos do que os descritos em outros estudos. Conclusões: A correlação estabelecida pode ser devida ao efeito dose-dependente do cromossomo X, visto que nossa revisão sugere que o número de cromossomos sexuais ou o desenvolvimento hormonal está associado a habilidades ou deficiências verbais, sociais e cognitivas.

Video-observed therapy (VOT) vs directly observed therapy (DOT) for tuberculosis treatment: A systematic review on adherence, cost of treatment observation, time spent observing treatment and patient satisfaction.

INTRODUCTION: Tuberculosis (TB) treatment demands strict adherence to multidrug regimens. Directly Observed Therapy (DOT) poses challenges, especially regarding adherence. With the popularization of smartphones, Video-Observed Therapy (VOT) has emerged as a promising alternative, allowing healthcare providers to remotely supervise patients taking their medications via video calls. OBJECTIVES: This systematic review critically assesses VOT's effectiveness compared to DOT, focusing on adherence, treatment costs, time spent supervising treatment, and patient satisfaction, aiming to optimize TB supervision methods worldwide. METHODS: Only studies that met the following criteria were eligible for inclusion in the systematic review: randomized trials; studies that compared VOT to DOT; studies involving patients diagnosed with pulmonary or extrapulmonary tuberculosis; studies that reported any of the desired outcomes; full-text articles available for review; and studies conducted in the English language. We excluded studies with the following attributes: studies that lacked a control group; case series or case reports; and previous systematic reviews. The search engines and databases MEDLINE, Embase, and Cochrane were used to find studies comparing Video-Observed Therapy (VOT) to Directly Observed Therapy (DOT). The following search phrases were used to look for papers that contained them in their title or abstract: ("Electronic Directly Observed Therapy" OR "Video-observed therapy" OR "Telemedicine" OR "Wirelessly observed therapy" OR "Smartphone-enabled video-observed") AND ("TUBERCULOSIS"). RESULTS: A systematic review of the literature revealed the following findings: in all Randomized Controlled Trials (RCTs), video-observed therapy (VOT) demonstrated non-inferiority in terms of treatment adherence compared to traditional directly observed therapy (DOT); VOT reduced costs where these outcomes were assessed in the RCTs; the use of VOT reduced the amount of time healthcare professionals spent supervising treatment in RCTs evaluating this aspect; VOT contributed to higher treatment satisfaction in RCTs where this outcome was measured. CONCLUSION: In this systematic review we emphasize the importance of Video-Observed Therapy (VOT) in the digital age for patients that have access to internet. Our findings show that VOT is comparable to DOT in terms of treatment adherence, but it is also cost-effective, improves patient satisfaction and takes less time for healthcare professionals to supervise.

Lime Stabilization of Tropical Soil for Resilient Pavements: Mechanical, Microscopic, and Mineralogical Characteristics.

Lime stabilization is a sustainable technique due to its use of local materials, increased durability, reduced maintenance, and improved resistance to water action. This paper examines the impact of lime stabilization on the mechanical, microscopic, and mineralogical properties of a tropical soil. Two types of lime, calcitic and dolomitic, were tested at 3% and 5% by weight. Compressive, indirect tensile and flexural test results and statistical analysis revealed that calcitic lime mixtures had higher strength and stiffness, whereas dolomitic lime mixtures exhibited greater deformability with higher tensile strain at break. Scanning electron microscopy indicated that the soil's porous matrix closed within 7 days for both lime types due to flocculation, with increased matrix interlocking over time. The calcitic lime mixture developed a more closed matrix compared to the dolomitic lime, which showed weaker cementing. X-ray diffraction analysis indicated higher consumption of clay minerals and a notable reduction in calcium hydroxide peaks in the lime-treated soils. The study concludes that calcitic lime provides better pavement performance for stabilizing the soil, enhancing its engineering properties while also being sustainable by reducing the need for raw material extraction and improving resilience to climate-related issues such as floods.

Turner syndrome and neuropsychological abnormalities: a review and case series.

OBJECTIVE: The objective of this study was to establish the genotype-phenotype correlation between karyotype results and the neurological and psychiatric alterations presented in patients with Turner syndrome (TS). METHODS: A retrospective study was conducted on the medical records of 10/140 patients with TS and neurophysiological abnormalities seen at a university hospital in southern Brazil. In addition, a literature review spanning the period from January 1, 2012 to January 1, 2023 was carried out using the PubMed and Virtual Health Library databases. RESULTS: Our study showed a potential correlation between neurological and psychiatric alterations in patients with TS. These findings are in accordance with those described in literature such as a high prevalence of learning or intellectual disabilities. However, our sample found more seizure episodes than those reported in other studies. CONCLUSIONS: The correlation established could be due to X chromosome dose-effect, as the review suggests that sex chromosome number and hormonal development can be associated with verbal, social, and cognitive skills or impairments.

Expanding the Phenotypic Spectrum of Pathogenic KIAA0586 Variants: From Joubert Syndrome to Hydrolethalus Syndrome.

KIAA0586 variants have been associated with a wide range of ciliopathies, mainly Joubert syndrome (JS, OMIM #616490) and short-rib thoracic dysplasia syndrome (SRTD, OMIM #616546). However, the hypothesis that this gene is involved with hydrolethalus syndrome (HSL, OMIM #614120) and orofaciodigital syndrome IV (OMIM #258860) has already been raised. Ciliopathies' clinical features are often overlapped despite differing in phenotype severity. Besides KIAA0586, HYLS1 and KIF7 are also known for being causative of ciliopathies, indicating that all three genes may have similar or converging genomic pathways. Overall, the genotypic and phenotypic spectrum of ciliopathies becomes wider and conflicting while more and more new variants are added to this group of disorders' molecular pot. In this case report we discuss the first Brazilian individual clinically diagnosed with hydrolethalus syndrome and molecular findings that demonstrate the role of KIAA0586 as a causative gene of a group of genetic disorders. Also, recent reports on individuals with intronic and exonic variants combined leading to ciliopathies support our patient's molecular diagnosis. At the same time, we discuss variable expressivity and overlapping features in ciliopathies.

Factors associated to mortality in children with critical COVID-19 and multisystem inflammatory syndrome in a resource-poor setting.

SARS-CoV-2 infection in children is usually asymptomatic/mild. However, some patients may develop critical forms. We aimed to describe characteristics and evaluate the factors associated to in-hospital mortality of patients with critical COVID-19/MIS-C in the Amazonian region. This multicenter prospective cohort included critically ill children (1 mo-18 years old), with confirmed COVID-19/MIS-C admitted to 3 tertiary Pediatric Intensive Care Units (PICU) in the Brazilian Amazon, between April/2020 and May/2023. The main outcome was in-hospital mortality and were evaluated using a multivariable Cox proportional regression. We adjusted the model for pediatric risk of mortality score version IV (PRISMIV) score and age/comorbidity. 266 patients were assessed with 187 in the severe COVID-19 group, 79 included in the MIS-C group. In the severe COVID-19 group 108 (57.8%) were male, median age was 23 months, 95 (50.8%) were up to 2 years of age. Forty-two (22.5%) patients in this group died during follow-up in a median time of 11 days (IQR, 2-28). In the MIS-C group, 56 (70.9%) were male, median age was 23 months and median follow-up was 162 days (range, 3-202). Death occurred in 17 (21.5%) patients with a median death time of 7 (IQR, 4-13) days. The mortality was associated with higher levels of Vasoactive Inotropic-Score (VIS), presence of acute respiratory distress syndrome (ARDS), higher levels of Erythrocyte Sedimentation Rate, (ESR) and thrombocytopenia. Critically ill patients with severe COVID-19 and MIS-C from the Brazilian Amazon showed a high mortality rate, within 12 days of hospitalization.

Qualidade de vida de portadores de neurofibromatose tipo 1: um protocolo de revisão de escopo / Quality of life of type 1 neurofibromatosis patients: a scoping review protocol

OBJETIVO: Mapear conceitos, achados e limitações acerca da qualidade de vida de crianças, adolescentes e adultos jovens portadores de neurofibromatose tipo 1. MÉTODO: Trata-se de um protocolo de revisão de escopo baseado nas diretrizes do Joanna Briggs Institute (JBI). A busca de dados será realizada nas plataformas PubMed/MEDLINE, EMBASE, Web of Science, Lilacs, CINAHL, Open Grey e Google Scholar. Os manuscritos encontrados serão organizados através da ferramenta Rayyan para identificação e exclusão de duplicatas. Na sequência, os artigos e demais materiais seguirão na mesma ferramenta para triagem e seleção de estudos elegíveis por dois pesquisadores independentes, sendo esse processo todo descrito em um fluxograma adaptado do Checklist PRISMA-ScR. Os dados extraídos dos manuscritos elegíveis serão apresentados em tabelas, quadros e fluxogramas, conforme pertinente. Os dados serão discutidos e inter-relacionados, com a finalidade de identificar potencialidades e limitações acerca do tema de pesquisa.

OBJECTIVE: To map concepts, findings, and limitations related to quality of life in children, adolescents, and young adults with neurofibromatosis type 1. METHOD: This is a scoping review protocol based on Joanna Briggs Institute (JBI) guidelines. Data searches will be conducted on PubMed/MEDLINE, EMBASE, Web of Science, Lilacs, CINAHL, Open Grey, and Google Scholar. The retrieved manuscripts will be organized using the Rayyan tool for duplicate identification and removal. Subsequently, the articles and other materials will be processed in the same tool for screening and selecting eligible studies by two independent researchers, and this entire process will be described in a flowchart adapted from the PRISMA-ScR checklist. As appropriate, data extracted from eligible manuscripts will be presented in tables, figures, and flowcharts. The data will be discussed and correlated to identify potential strengths and limitations related to the research topic.

Fluorescence in situ hybridization (FISH) as an irreplaceable diagnostic tool for Williams-Beuren syndrome in developing countries: a literature review.

OBJECTIVE: The aim of this study was to sum up and characterize all Williams-Beuren syndrome cases diagnosed by fluorescence in situ hybridization (FISH) since its implementation, as well as to discuss FISH as a cost-effective methodology in developing countries. DATA SOURCE: From January 1986 to January 2022, articles were selected using the databases in PubMed (Medline) and SciELO. The following terms were used: Williams syndrome and In Situ Hybridization, Fluorescence. Inclusion criteria included Williams-Beuren syndrome cases diagnosed by FISH with a stratified phenotype of each patient. Only studies written in English, Spanish, and Portuguese were included. Studies with overlapping syndromes or genetic conditions were excluded. DATA SYNTHESIS: After screening, 64 articles were included. A total of 205 individuals with Williams-Beuren syndrome diagnosed by FISH were included and further analyzed. Cardiovascular malformations were the most frequent finding (85.4%). Supravalvular aortic stenosis (62.4%) and pulmonary stenosis (30.7%) were the main cardiac alterations described. CONCLUSIONS: Our literature review reinforces that cardiac features may be the key to early diagnosis in Williams-Beuren syndrome patients. In addition, FISH may be the best diagnostic tool for developing nations that have limited access to new technologic resources.

Congenital Heart Defects and 22q11.2 Deletion Syndrome: A 20-Year Update and New Insights to Aid Clinical Diagnosis.

Congenital heart defects (CHDs) are one of the most prevalent clinical features described in individuals diagnosed with 22q11.2 deletion syndrome (22q11.2DS). Therefore, cardiac malformations may be the main finding to refer for syndrome investigation, especially in individuals with a mild phenotype. Nowadays, different cytogenetic methodologies have emerged and are used routinely in research laboratories. Hence, choosing an efficient technology and providing an accurate interpretation of clinical findings is crucial for 22q11.2DS patient's diagnosis. This systematic review provides an update of the last 20 years of research on 22q11.2DS patients with CHD and the investigation process behind each diagnosis. A search was performed in PubMed, Embase, and LILACS using all entry terms to DiGeorge syndrome, CHDs, and cytogenetic analysis. After screening, 60 papers were eligible for review. We present a new insight of ventricular septal defect as a possible pivotal cardiac finding in individuals with 22q11.2DS. Also, we describe molecular technologies and cardiac evaluation as valuable tools in order to guide researchers in future investigations.

22q11 Copy Number Variations in a Brazilian Cohort of Children with Congenital Heart Disorders.

Introduction: Congenital heart disease (CHD) is the most common type of congenital defect reported to be one of the leading causes of mortality in the first year of life. Microdeletion and microduplication syndromes (MMS) are associated with cardiac malformations. Understanding which genetic factors are involved in these conditions directly impacts treatment decisions. We aimed to identify the occurrence of genetic alterations and their association with MMS in CHD pediatric patients evaluated in a reference service of Southern Brazil. Methods: Participants were recruited during 2010 in the intensive care unit of a pediatric hospital. MMs and regions of chromosome 22 were screened by SALSA MLPA Probemix P245 Microdeletion Syndromes-1A kit for detection of copy number variations (CNVs). Results: MMS were detected in 11 from 207 patients (5.3%). Heterozygous deletion in the 22q11.2 chromosome region was the most prevalent CNV (5 from 11 patients). Also, atypical RTDR1 deletion and 22q11.2 duplication were detected. MLPA was able to reveal microdeletions in SNRPN and NF1 genes in patients with a normal karyotype and FISH. Conclusion: Our study reports the prevalence and variability of genomic alterations associated with MMS in CHD pediatric patients. The results by MLPA are of great help in planning and specialized care.

Comensalidade, câncer e sobrevivência: uma metassíntese qualitativa sobre experiências alimentares de pacientes após o diagnóstico de câncer / Commensality, cancer and survival: A qualitative meta-synthesis of patients' food experiences after cancer diagnosis

Resumo Objetivo Compreender as experiências e as práticas alimentares a partir do diagnóstico de câncer. Método: Trata-se de uma pesquisa bibliográfica, do tipo metassíntese qualitativa. Utilizou-se a diretriz ENTREQ como protocolo, tendo como pergunta norteadora: "Quais são as experiências e as práticas alimentares de indivíduos após o diagnóstico de câncer?". A busca foi realizada nas bases de dados Lilacs, Pubmed, Embase e Food Science and Techonology, a partir da combinação de palavras-chave relacionadas à alimentação e nutrição, ao adoecimento por câncer e à pesquisa qualitativa, publicados entre 2015 e 2020, em português, inglês e espanhol. Método Foram encontrados 414 artigos e excluídos 396, após leitura dos títulos e resumos. Além dos 18 artigos potenciais, foram incluídos cinco artigos de outras fontes, totalizando 23. Foram identificadas três categorias empíricas: ruptura da trajetória alimentar e estratégias de adaptação; reconstrução da identidade; e vicissitudes da comensalidade. Conclusões As perdas relacionadas à alimentação impactam na existencialidade do ser, na expressão da identidade e nas relações sociais, podendo levar ao isolamento e a desritualização da alimentação. As mudanças físicas podem levar a distúrbios de imagem corporal e sofrimento psíquico. Em decorrência dos sintomas de impacto nutricional, a família é o suporte emocional para reorganização da alimentação.

Abstract Objective To understand the experiences and eating practices from the diagnosis of cancer. Method This is a bibliographic research, of the qualitative meta-synthesis type, using the ENTREQ guideline as a protocol, with the guiding question: "What are the experiences and eating practices of individuals after being diagnosed with cancer?". The search was carried out in the Lilacs, Pubmed, Embase and Food Science and Techonology databases based on the combination of keywords related to food and nutrition, illness from cancer and qualitative research, published between 2015 and 2020, in Portuguese, English and Spanish. Results 414 articles were found and 396 were excluded after reading the titles and abstracts. In addition to the 18 potential articles, 5 articles from other sources were included, totaling 23. Three empirical categories were identified: disruption of the food trajectory and adaptation strategies; reconstruction of identity; and vicissitudes of commensality. Conclusions Losses related to food impact the existentiality of being, the expression of identity and social relationships, which can lead to the isolation and de-ritualization of food. Physical changes can lead to body image disorders and psychological distress. Due to the symptoms of nutritional impact, the family is the emotional support for the reorganization of food.

Fluorescence in situ hybridization (FISH) as an irreplaceable diagnostic tool for Williams-Beuren syndrome in developing countries: a literature review / Hibridização in situ fluorescente (FISH) como ferramenta diagnóstica insubstituível para a síndrome de Williams-Beuren em países em desenvolvimento: uma revisão de literatura

ABSTRACT Objective: The aim of this study was to sum up and characterize all Williams-Beuren syndrome cases diagnosed by fluorescence in situ hybridization (FISH) since its implementation, as well as to discuss FISH as a cost-effective methodology in developing countries. Data source: From January 1986 to January 2022, articles were selected using the databases in PubMed (Medline) and SciELO. The following terms were used: Williams syndrome and In Situ Hybridization, Fluorescence. Inclusion criteria included Williams-Beuren syndrome cases diagnosed by FISH with a stratified phenotype of each patient. Only studies written in English, Spanish, and Portuguese were included. Studies with overlapping syndromes or genetic conditions were excluded. Data synthesis After screening, 64 articles were included. A total of 205 individuals with Williams-Beuren syndrome diagnosed by FISH were included and further analyzed. Cardiovascular malformations were the most frequent finding (85.4%). Supravalvular aortic stenosis (62.4%) and pulmonary stenosis (30.7%) were the main cardiac alterations described. Conclusions: Our literature review reinforces that cardiac features may be the key to early diagnosis in Williams-Beuren syndrome patients. In addition, FISH may be the best diagnostic tool for developing nations that have limited access to new technologic resources.

RESUMO Objetivo: Caracterizar todos os casos de síndrome de Williams-Beuren (SWB) diagnosticados por hibridização in situ fluorescente (FISH) desde sua implementação, assim como discutir a relação custo-benefício da metodologia de FISH em países em desenvolvimento. Fontes de dados: Entre janeiro de 1986 e janeiro de 2022 foi realizada uma busca nas bases de dados PubMed (Medical Literature Analysis and Retrieval System Online — Medline) e Scientific Electronic Library Online (SciELO) usando os seguintes termos: síndrome de Williams e hibridização in situ fluorescente. O critério de inclusão utilizado foi conter a descrição detalhada de caso(s) de SWB por FISH. Apenas estudos escritos em inglês, espanhol e português foram incluídos. Trabalhos que apresentavam sobreposição de síndromes/condições genéticas foram excluídos. Síntese dos dados: Após os processos de inclusão, 64 artigos e 205 indivíduos com SWB diagnosticados por meio do método de FISH foram incluídos. O achado mais frequente entre os indivíduos foi a presença de algum tipo de malformação cardíaca (85,4%). A estenose aórtica supravalvar (62,4%) e a estenose pulmonar (30,7%) foram as alterações cardíacas mais descritas. A maioria dos estudos era proveniente dos continentes Europa, Ásia e América do Norte. Conclusões: A presente revisão de literatura reitera que as malformações cardíacas podem ser a chave para o diagnóstico precoce em pacientes com SWB. Ainda, a técnica de FISH parece ser a melhor ferramenta de diagnóstico para os países em desenvolvimento, cujo acesso às novas tecnologias ainda é escasso.

DHA/EPA supplementation decreases anxiety-like behaviour, but it does not ameliorate metabolic profile in obese male rats.

Obesity is a major public health problem that predisposes to several diseases and higher mortality in patients with COVID-19. Obesity also generates neuroinflammation, which predisposes to the development of neuropsychiatric diseases. Since there is a lack of effective treatments for obesity, the search for new strategies to reverse its consequences is urgent. In this perspective, the anti-inflammatory properties of omega-3 polyunsaturated fatty acids such as DHA/EPA might reduce the harmful effects of obesity. Here, we used the cafeteria diet (CAF) model to induce obesity in Wistar rats. Animals received ultra-processed food for 20 weeks, and DHA/EPA supplementation (500 mg/kg per d) was performed between the 16th and the 20th week. At the end of the experiment, it was evaluated: body weight, visceral fat deposition, plasma glucose, insulin and triglycerides, and it was also measured the levels of inflammatory cytokines TNF-α and IL-6 in plasma and liver, and TNF-α in the prefrontal cortex. The elevated plus maze test was performed to analyse anxiety-like behaviour. Our results demonstrated that DHA/EPA could not reverse weight and fat gain and did not modify plasma dosages. However, there was a decrease in IL-6 in the liver (DHA/EPA effect: P = 0.023) and TNF-α in the brain (CAF compared with CAF + DHA/EPA, P < 0.05). Also, there was a decrease in the anxiety index in CAF + DHA/EPA compared with the CAF group (P < 0.01). Thus, DHA/EPA supplementation is helpful to reverse the consequences of obesity in the brain.

A child with cat-eye syndrome and oculo-auriculo-vertebral spectrum phenotype: A discussion around molecular cytogenetic findings.

Cat eye syndrome (CES) is a rare chromosomal disorder that may be evident at birth. A small supernumerary chromosome is present, frequently has 2 centromeres, is bisatellited, and represents an inv dup(22)(q11) in those affected. It's known that the 22q11 region is associated with disorders involving higher and lower gene dosages. Conditions such as CES, 22q11 microduplication syndrome (Dup22q11) and oculoauriculovertebral spectrum phenotype (OAVS) may share genes belonging to this same region, which is known to have a predisposition to chromosomal rearrangements. The conditions, besides being related to chromosome 22, also share similar phenotypes. Here we have added a molecular evaluation update and results found of the first patient described with CES and OAVS phenotype, trying to explain the potential mechanism involved in the occurrence of this association.

Pseudohypoparathyroidism with Ectopic Calcification and 22q11 Deletion Syndrome: A Rare Case.

Ectopic calcification in soft tissue is associated with several disorders including pseudohypoparathyroidism (PHP), which is characterized by resistance or nonresponse to parathyroid hormone (PTH) function. Association between PHP and 22q11DS, also known as DiGeorge syndrome, is rare, especially in children. We describe a newborn girl diagnosed with 22q11DS, presenting ectopic calcifications in soft tissue and suspicion of PHP. PTH function showed values close to the upper limit of the reference value. Radiology showed bone callus in the right wrist. PHP can be a new clinical finding associated with 22q11DS. Parathyroid function investigation in individuals with 22q11DS, presenting bone dysmorphisms and/or calcium metabolism alterations, should be considered.

Candidate genes of oculo-auriculo-vertebral spectrum in 22q region: A systematic review.

Oculo-auriculo-vertebral spectrum (hemifacial microsomia/OAVS, OMIM #164210) is a heterogenous and congenital condition caused by a morphogenesis defect of the first and second pharyngeal arches. Etiology includes unknown genetic, environmental factors and chromosomal alterations, which 22q11.2 region is the most frequently reported. Several candidate genes for OAVS have been proposed; however, none has been confirmed as causative of the phenotype. This review aims to sum up all clinical and molecular findings in 22q region of individuals diagnosed with OAVS and to investigate genes that may be involved in the development of the spectrum. A search was performed in PubMed using all entry terms to OAVS and Chromosome 22q11. After screening, 11 papers were eligible for review. Deletions and duplications in the q11.2 region were the most frequent (18/22) alterations reported and a total of 68 genes were described. Our systematic review reinforces the hypothesis that 22q11 region is a candidate locus for OAVS as well as CLTCL1, GSC2, HIRA, MAPK1, TBX1, and YPEL1 as potential candidates genes for genotype-phenotype correlation. Complementary studies regarding genes interaction involved in the 22q11 region are still necessary in the search for a genotype-phenotype association, since the diagnosis of OAVS is a constant medical challenge.

Congenital Heart Defects and Dysmorphic Facial Features in Patients Suspicious of 22q11.2 Deletion Syndrome in Southern Brazil.

22q11.2 deletion syndrome (22q11.2DS) is considered one of the most frequently observed chromosomal abnormalities in association with congenital heart disease (CHD), which can also include some combination of other features. Thus, the aim of this work was to verify the profile of dysmorphic features and heart defects found in patients referred to a reference center in Southern Brazil with clinical findings suggestive of 22q11.2DS. In the overall sample group, only patients with dysmorphic facial features (skull, eyes, ear, and nose) associated with CHD (obstructive pulmonary valve ring, truncus arteriosus, and bicuspid aortic valve associated with atrial septal defect and/or right aortic arch) had a 22q11.2 deletion. These findings proved to be reliable clinical criteria for referral to perform fluorescent in situ hybridization investigation for 22q11.2 deletion.

Microarray-Based Comparative Genomic Hybridization, Multiplex Ligation-Dependent Probe Amplification, and High-Resolution Karyotype for Differential Diagnosis Oculoauriculovertebral Spectrum: A Systematic Review.

Oculoauriculovertebral spectrum (OAVS) is a rare class of heterogenous congenital craniofacial malformation conditions of unknown etiology. Although classic OAVS has been described as hemifacial microsomia with facial asymmetry and microtia, there is no consensus regarding clinical criteria for diagnosis or genetic cause. This systematic review aims to assess the applicability of high-resolution (HR) karyotype, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification (MLPA), and microarray-based comparative genomic hybridization (array-CGH) for differential diagnosis of OAVS. A search was performed in PubMed and Web of Science using all entry terms to the following descriptors: Goldenhar's syndrome, cytogenetic analysis, hybridization in situ, fluorescent, comparative genomic hybridization, multiplex polymerase chain reaction, whole genome sequencing, and karyotype analysis methods. After screening, 25 articles met eligibility. Of the included studies, 59 individuals had a genetic alteration identified. Array-CGH, MLPA, and HR karyotype appear to be viable approaches for molecular diagnosis in OAVS. Heterogeneity is a hallmark of OAVS. Establishing an enhanced framework for diagnosis would inform clinical decision making, and better resource utilization could improve health care facility efficiency and economy.

Description of clinical aspects and microscopy of the hair shaft of a carrier of familial monilethrix / Descrição dos aspectos clínicos e da microscopia da haste capilar de um portador de monilétrix familiar

ABSTRACT Monilethrix is a genetic condition that affects the hair shaft. We describe a family with this disease, focusing on its clinical aspects and microscopic hair characteristics. The patient was a 10-year-old female with history of hypotrichosis. In addition to diffuse alopecia, there was brittle hair, with ruptures in the hair shaft at different levels. The hair had a nodular appearance at naked eye. Other family members had the same symptoms, what indicates an autosomal dominant pattern of inheritance. Microscopic analysis revealed capillary fibers with areas of elliptical nodular appearance interspersed with regions of dystrophic constriction.

RESUMO A monilétrix é uma condição genética que acomete a haste capilar. Descrevemos uma família com essa doença, enfocando seus aspectos clínicos e as características microscópicas do cabelo. A paciente era do sexo feminino, 10 anos de idade, e apresentava história de hipotricose. Além da alopecia difusa, notava-se um cabelo quebradiço, com rupturas na haste capilar em diferentes níveis. Os cabelos possuíam um aspecto nodular a olho nu. Outros membros da família apresentavam os mesmos sintomas, o que indica um padrão de herança autossômica dominante. A análise microscópica revelou fibras capilares com áreas de aparência nodular elíptica, intercaladas por regiões de constrição distrófica.

Autopsy findings of a child with left atrial isomerism associated with pulmonary agenesis / Achados de autópsia de uma criança com isomerismo atrial esquerdo associado à agenesia pulmonar

ABSTRACT Isomerism is a rare laterality defect. Our aim was to describe the autopsy findings of a child with left atrial isomerism (LAI) and pulmonary agenesis (PA), an association still not described in the literature. Fetal ultrasound revealed right renal agenesis, single umbilical artery and polyhydramnios. Echocardiography revealed a complex heart defect with LAI. The child died minutes after birth. Autopsy confirmed the prenatal findings and revealed the presence of unilateral PA, complex vascular abnormalities and polysplenia. Despite its rarity, health professionals should be aware for the possibility of such an association.

RESUMO O isomerismo é um defeito de lateralidade raro. Nosso objetivo foi descrever os achados da autópsia de uma criança com isomerismo atrial esquerdo (IAE) e agenesia pulmonar (AP), uma associação ainda não descrita na literatura. A ultrassonografia fetal revelou agenesia renal direita, artéria umbilical única e polidrâmnio; a ecocardiografia apresentou defeito cardíaco complexo com IAE. A criança morreu minutos após o nascimento. A autópsia confirmou os achados pré-natais e revelou a presença de agenesia pulmonar unilateral, anormalidades vasculares complexas e polisplenia. Apesar de sua raridade, profissionais da saúde devem estar cientes da possibilidade dessa associação.