Magnification and Refocusing Comparison in Cataract Surgery Using a Heads-Up Three-Dimensional Visualization System versus Conventional Binocular Microscopy.

Purpose: To compare magnification and refocusing during phacoemulsification with the NGENUITY®â€¯3-D Visualization System (3-D) versus the conventional microscope (CM) OPMI LUMERA 700. Setting: This study was performed in the Department of Anterior Segment of the Fundación Hospital Nuestra Señora de la Luz. Design: Prospective, randomized, cross-sectional, multi-surgeon, and comparative study. Methods: This study enrolled 100 patients (eyes) scheduled for phacoemulsification to measure the number of times changes in focusing and magnification were needed during cataract surgery. Results: Our study included 100 patients. From the endpoints evaluated, "zoom-in" showed statistically significant differences for all of the four predefined cataract surgery steps (means: Step 1, 0.38 (CM) vs 0.08 (3-D); Step 2, 0.36 (CM) vs 0.06 (3-D); Step 3, 0.54 (CM) vs 0.22 (3-D); Step 4, 0.56 (CM) vs 0.24 (3-D); all comparisons, p <0.05). In Step 4, there was a statistically significant increased use of "focus-out" for the 3-D system (mean 0.16 (CM) vs 0.58 (3-D); p <0.05). "Focus-in" and "zoom-out" showed no group differences for all steps. The duration of surgery with the 3-D system was longer at each step and overall. The percentage of light intensity did not show a statistically significant difference between both systems, with a mean of 99.45 for CM vs 98.43% for the heads-up system. Conclusion: The heads-up 3-D system is a safe option that offers excellent magnification for anterior segment visualization. The surgical time is longer, but adjusting settings like light intensity and brightness may facilitate some surgical steps early in the learning curve.

A Brazilian case of IFAP syndrome with severe congenital ichthyosis and limb malformations caused by a rare variant in MBTPS2.

OBJECTIVE: The classic triad, which defines IFAP syndrome, is ichthyosis follicularis, alopecia, and photophobia. It is a rare X-linked genetic disorder characterized by multiple congenital anomalies with variable severity, caused by pathogenic variants in the MBTPS2 gene, which encodes a zinc metalloprotease that is essential for normal development. This study aimed to report a case of a Brazilian patient with IFAP syndrome presenting skeletal anomalies, which is a rare finding among patients from different families. CASE DESCRIPTION: We describe a male proband with IFAP syndrome showing severe ichthyosis congenita, cryptorchidism, limb malformation, and comprising the BRESHECK syndrome features. Using whole-exome sequencing, we identified a rare missense variant in hemizygosity in the MBTPS2 gene, which had not been identified in other family members. COMMENTS: This is the first diagnosis of IFAP syndrome in Brazil with a molecular investigation. The present case study thus expands our knowledge on the mutational spectrum of MBPTS2 associated with IFAP syndrome.

A Brazilian case of IFAP syndrome with severe congenital ichthyosis and limb malformations caused by a rare variant in MBTPS2 / Um caso brasileiro de síndrome IFAP com ictiose congênita grave e malformações de membros causadas por uma variante rara em MBTPS2

Abstract Objective: The classic triad, which defines IFAP syndrome, is ichthyosis follicularis, alopecia, and photophobia. It is a rare X-linked genetic disorder characterized by multiple congenital anomalies with variable severity, caused by pathogenic variants in the MBTPS2 gene, which encodes a zinc metalloprotease that is essential for normal development. This study aimed to report a case of a Brazilian patient with IFAP syndrome presenting skeletal anomalies, which is a rare finding among patients from different families. Case description: We describe a male proband with IFAP syndrome showing severe ichthyosis congenita, cryptorchidism, limb malformation, and comprising the BRESHECK syndrome features. Using whole-exome sequencing, we identified a rare missense variant in hemizygosity in the MBTPS2 gene, which had not been identified in other family members. Comments: This is the first diagnosis of IFAP syndrome in Brazil with a molecular investigation. The present case study thus expands our knowledge on the mutational spectrum of MBPTS2 associated with IFAP syndrome.

RESUMO Objetivo: A clássica tríade de ictiose folicular, alopecia e fotofobia dá nome a uma síndrome rara de origem genética com herança ligada ao cromossomo X (síndrome IFAP, do inglês Ichthyosis Follicularis, Alopecia, and Photophobia). Esta é uma síndrome caracterizada por múltiplas anomalias congênitas de expressividade variável, causada por variantes patogênicas no gene MBTPS2, que codifica uma zinco-metaloprotease essencial para o desenvolvimento normal humano. O objetivo deste estudo é apresentar o relato de caso de um paciente brasileiro com síndrome IFAP que apresentou anomalias esqueléticas, um achado raro entre os pacientes de diferentes famílias. Descrição do caso: Apresentamos um probando do sexo masculino com síndrome IFAP, com ictiose congênita grave, criptorquidia, malformação de membros e as características da síndrome de BRESHECK. Por meio do sequenciamento do exoma completo, identificamos uma variante rara do tipo missense, em hemizigose, no gene MBTPS2, não identificada em outros membros da família. Comentários: Este é o primeiro diagnóstico de síndrome IFAP no Brasil com investigação molecular. A análise molecular e a descrição de uma variante rara no gene MBPTS2 expandem nosso conhecimento sobre o espectro mutacional desse gene associado à síndrome IFAP.

Minimal Critical Region and Genes for a Typical Presentation of Langer-Giedion Syndrome.

Langer-Giedion syndrome (LGS) is caused by a contiguous deletion at 8q23q24, characterized by exostoses, facial, ectodermal, and skeletal anomalies, and, occasionally, intellectual disability. LGS patients have been diagnosed clinically or by routine cytogenetic techniques, hampering the definition of an accurate genotype-phenotype correlation for the syndrome. We report two unrelated patients with 8q23q24 deletions, characterized by cytogenomic techniques, with one of them, to our knowledge, carrying the smallest deletion reported in classic LGS cases. We assessed the pathogenicity of the deletion of genes within the 8q23q24 region and reviewed other molecularly confirmed cases from the literature. Our findings suggest a 3.2-Mb critical region for a typical presentation of the syndrome, emphasizing the contribution of the TRPS1, RAD21, and EXT1 genes' haploinsufficiency, and facial dysmorphisms as well as bone anomalies as the most frequent features among patients with LGS. We also suggest a possible role for the CSMD3 gene, whose deletion seems to contribute to central nervous system anomalies. Since studies performing such correlation for LGS patients are limited, our data contribute to improving the ge-notype-phenotype characterization for LGS patients.

Using Online Mendelian Inheritance in Man in low- and middle-income countries.

Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders, has been used in the low- and middle-income countries largely as a tool for improving clinical care, teaching genetics and genomics, and for clinical and research analysis of next-generation sequencing. By facilitating free access to curated, updated, and comprehensive information in genetics and genomics, OMIM has led to better clinical care and research advancement in countries where clinicians and researchers in private or public hospitals and universities cannot afford to pay for other resources including journal subscriptions.

Generation of two human induced pluripotent stem cell (hiPSC) lines derived from unrelated Marfan Syndrome patients.

Marfan Syndrome (MFS) is a pleiotropic and autosomal dominant condition caused by pathogenic variants in FBN1. Although fully penetrant, clinical variability is frequently observed among patients and there are only few genotype-phenotype correlations described so far. Here, we describe the generation and characterization of hiPSC lines derived from two unrelated MFS patients harboring heterozygous variants in FBN1. Human iPSCs were obtained from erythroblasts reprogrammed with episomal vectors carrying the reprogramming factors OCT4, SOX2, KLF4, c-MYC and LIN-28, and characterized according to established criteria. Differentiated cells demonstrated different patterns of fibrillin-1 expression suggesting different molecular mechanisms between the two patients.

Novel MYT1 variants expose the complexity of oculo-auriculo-vertebral spectrum genetic mechanisms.

Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder characterized by anomalies mainly involving the structures derived from the first and second pharyngeal arches. The spectrum presents with heterogeneous clinical features and complex etiology with genetic factors not yet completely understood. To date, MYT1 is the most important gene unambiguously associated with the spectrum and with functional data confirmation. In this work, we aimed to identify new single nucleotide variants (SNVs) affecting MYT1 in a cohort of 73 Brazilian patients diagnosed with OAVS. In addition, we investigated copy number variations (CNVs) encompassing this gene or its cis-regulatory elements and compared the frequency of these events in patients versus a cohort of 455 Brazilian control individuals. A new SNV, predicted as likely deleterious, was identified in five unrelated patients with OAVS. All five patients presented hearing impairment and orbital asymmetry suggesting an association with the variant. CNVs near MYT1, located in its neighboring topologically associating domain (TAD), were found to be enriched in patients when compared to controls, indicating a possible involvement of this region with OAVS pathogenicity. Our findings highlight the genetic complexity of the spectrum that seems to involve more than one variant type and inheritance patterns.

Spread of X-chromosome inactivation into autosomal regions in patients with unbalanced X-autosome translocations and its phenotypic effects.

Patients with unbalanced X-autosome translocations are rare and usually present a skewed X-chromosome inactivation (XCI) pattern, with the derivative chromosome being preferentially inactivated, and with a possible spread of XCI into the autosomal regions attached to it, which can inactivate autosomal genes and affect the patients' phenotype. We describe three patients carrying different unbalanced X-autosome translocations, confirmed by G-banding karyotype and array techniques. We analyzed their XCI pattern and inactivation spread into autosomal regions, through HUMARA, ZDHHC15 gene assay and the novel 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, and identified an extremely skewed XCI pattern toward the derivative chromosomes for all the patients, and a variable pattern of late-replication on the autosomal regions of the derivative chromosomes. All patients showed phenotypical overlap with patients presenting deletions of the autosomal late-replicating regions, suggesting that the inactivation of autosomal segments may be responsible for their phenotype. Our data highlight the importance of the XCI spread into autosomal regions for establishing the clinical picture in patients carrying unbalanced X-autosome translocations, and the incorporation of EdU as a novel and precise tool to evaluate the inactivation status in such patients.

Clinical and molecular evaluation of 13 Brazilian patients with Gomez-López-Hernández syndrome.

We aim to characterize patients with Gomez-López-Hernández syndrome (GLHS) clinically and to investigate them molecularly. A clinical protocol, including a morphological and neuropsychological assessment, was applied to 13 patients with GLHS. Single-nucleotide polymorphism (SNP) array and whole-exome sequencing were undertaken; magnetic resonance imaging was performed in 12 patients, including high-resolution, heavily T2-weighted sequences (HRT2) in 6 patients to analyze the trigeminal nerves. All patients presented alopecia; two did not present rhombencephalosynapsis (RES); trigeminal anesthesia was present in 5 of the 11 patients (45.4%); brachycephaly/brachyturricephaly and mid-face retrusion were found in 84.6 and 92.3% of the patients, respectively. One patient had intellectual disability. HRT2 sequences showed trigeminal nerve hypoplasia in four of the six patients; all four had clinical signs of trigeminal anesthesia. No common candidate gene was found to explain GLHS phenotype. RES does not seem to be an obligatory finding in respect of GLHS diagnosis. We propose that a diagnosis of GLHS should be considered in patients with at least two of the following criteria: focal non-scarring alopecia, rhombencephalosynapsis, craniofacial anomalies (brachyturrycephaly, brachycephaly or mid-face retrusion), trigeminal anesthesia or anatomic abnormalities of the trigeminal nerve. Studies focusing on germline whole genome sequencing or DNA and/or RNA sequencing of the alopecia tissue may be the next step for the better understanding of GLHS etiology.

Overlapping phenotype comprising Kenny-Caffey type 2 and Sanjad-Sakati syndromes: The first case report.

Kenny-Caffey syndrome (KCS) is a rare hereditary skeletal disorder involving hypoparathyroidism. The autosomal dominant form (KCS2), caused by heterozygous pathogenic variants in the FAM111A gene, is distinguished from the autosomal recessive form (KCS1) and Sanjad-Sakati syndrome (SSS), both caused by pathogenic variants in the tubulin folding cofactor E (TBCE) gene, by the absence of microcephaly and intellectual disability. We present a patient with KCS2 caused by a de novo pathogenic variant c.1706G>A (p.Arg569His) in FAM111A gene, presenting intellectual disability and microcephaly, which are considered to be typical signs of SSS. We suggest that KCS1, KCS2, and SSS may not represent mutually exclusive clinical entities, but possibly an overlapping spectrum.

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.

TRANSLATION, CULTURAL ADAPTATION, AND EVIDENCE OF INSTRUMENT VALIDITY FOR A MORPHOLOGICAL EXAMINATION PERFORMED IN CHILDREN WITH AUTISM SPECTRUM DISORDER.

OBJECTIVE: For every 100 random children diagnosed with autism, at least 20 have morphological abnormalities, often associated with syndromes. Brazil does not have a standardized and validated instrument for morphological physical examination. This study aimed to translate into Brazilian Portuguese and culturally adapt the clinical signs described in the Autism Dysmorphology Measure, as well as validate the instrument in a sample of children with autism. METHODS: The original instrument was translated, culturally adapted, and published in full, following traditional procedures for translation, back-translation, and terminology adaptation according to the Nomina Anatomica. The sample included 62 children from a published multicenter study, with intelligence quotient between 50-69, of both genders, with chronological age between 3-6 years. Two clinical geneticists performed the morphological physical examination, which consisted of investigating 82 characteristics assessing 12 body areas. We used Cohen's Kappa coefficient to evaluate the agreement between the two observers. RESULTS: The final version of the instrument - translated into Brazilian Portuguese and culturally adapted - showed high agreement between the two observers. CONCLUSIONS: The translated instrument meets all international criteria, and minor anomalies and their clinical descriptions were standardized and are recognizable for physicians not specialized in genetics.

Translation, cultural adaptation, and evidence of instrument validity for a morphological examination performed in children with autism spectrum disorder / Tradução, adaptação cultural e evidência de validade de instrumento para o exame morfológico aplicado a crianças com transtorno do espectro autista

ABSTRACT Objective: For every 100 random children diagnosed with autism, at least 20 have morphological abnormalities, often associated with syndromes. Brazil does not have a standardized and validated instrument for morphological physical examination. This study aimed to translate into Brazilian Portuguese and culturally adapt the clinical signs described in the Autism Dysmorphology Measure, as well as validate the instrument in a sample of children with autism. Methods: The original instrument was translated, culturally adapted, and published in full, following traditional procedures for translation, back-translation, and terminology adaptation according to the Nomina Anatomica. The sample included 62 children from a published multicenter study, with intelligence quotient between 50-69, of both genders, with chronological age between 3-6 years. Two clinical geneticists performed the morphological physical examination, which consisted of investigating 82 characteristics assessing 12 body areas. We used Cohen's Kappa coefficient to evaluate the agreement between the two observers. Results: The final version of the instrument - translated into Brazilian Portuguese and culturally adapted - showed high agreement between the two observers. Conclusions: The translated instrument meets all international criteria, and minor anomalies and their clinical descriptions were standardized and are recognizable for physicians not specialized in genetics.

RESUMO Objetivo: Entre 100 crianças, não selecionadas, com diagnóstico de autismo, pelo menos 20 apresentam anomalias morfológicas, quase sempre associadas a síndromes. Não há no Brasil instrumento de exame físico morfológico padronizado e validado. O objetivo foi traduzir para o português do Brasil e adaptar culturalmente os sinais clínicos descritos no Autism Dysmorphology Measure, assim como procurar evidências de validade quando aplicado a uma amostra de crianças com autismo. Métodos: Foram feitas a tradução e a adaptação cultural do instrumento original, publicado na íntegra. Foram adotados os procedimentos tradicionais de tradução, retrotradução e adaptação da terminologia segundo a Nomina Anatomica. Foram incluídas na amostra 62 crianças com quociente de inteligência entre 50 e 69, de ambos os sexos, com idade cronológica entre três e seis anos, provenientes de estudo multicêntrico com os procedimentos metodológicos já publicados. O exame físico morfológico foi realizado por dois médicos geneticistas e consistiu na pesquisa de 82 características que avaliam 12 áreas corporais. Para avaliar a concordância entre os dois observadores foi utilizado o coeficiente Kappa de Cohen. Resultados: A versão final do instrumento traduzido e adaptado culturalmente ao português do Brasil mostrou alta concordância entre os dois observadores. Conclusões: O instrumento traduzido preenche todos os critérios propostos internacionalmente e o reconhecimento das anomalias menores e sua descrição clínica estão padronizados e são de fácil reconhecimento aos médicos não especialistas em genética.

A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case.

BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms associated with several comorbidities caused by SHANK3 loss-of-function mutations. Although SHANK3 haploinsufficiency has been associated with the major neurological symptoms of PMS, it cannot explain the clinical variability seen among individuals. Our goals were to characterize a Brazilian cohort of PMS individuals, explore the genotype-phenotype correlation underlying this syndrome, and describe an atypical individual with mild phenotype. METHODOLOGY: A total of 34 PMS individuals were clinically and genetically evaluated. Data were obtained by a questionnaire answered by parents, and dysmorphic features were assessed via photographic evaluation. We analyzed 22q13.3 deletions and other potentially pathogenic copy number variants (CNVs) and also performed genotype-phenotype correlation analysis to determine whether comorbidities, speech status, and ASD correlate to deletion size. Finally, a Brazilian cohort of 829 ASD individuals and another independent cohort of 2297 ID individuals was used to determine the frequency of PMS in these disorders. RESULTS: Our data showed that 21% (6/29) of the PMS individuals presented an additional rare CNV, which may contribute to clinical variability in PMS. Increased pain tolerance (80%), hypotonia (85%), and sparse eyebrows (80%) were prominent clinical features. An atypical case diagnosed with PMS at 18 years old and IQ within the normal range is here described. Among Brazilian ASD or ID individuals referred to CNV analyses, the frequency of 22q13.3 deletion was 0.6% (5/829) and 0.61% (15/2297), respectively. Finally, renal abnormalities, lymphedema, and language impairment were found to be positively associated with deletion sizes, and the minimum deletion to cause these abnormalities is here suggested. CONCLUSIONS: This is the first work describing a cohort of Brazilian individuals with PMS. Our results confirm the impact of 22q13 deletions on ASD and several comorbidities, such as hypotonia. The estimation of a minimal deletion size for developing lymphedema and renal problem can assist prediction of prognosis in PMS individuals, particularly those diagnosed in early infancy. We also identified one atypical individual carrying SHANK3 deletion, suggesting that resilience to such mutations occurs. This case expands the clinical spectrum of variability in PMS and opens perspectives to identify protective mechanisms that can minimize the severity of this condition.

Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity.

BACKGROUND: Syndromic obesity is an umbrella term used to describe cases where obesity occurs with additional phenotypes. It often arises as part of a distinct genetic syndrome with Prader-Willi syndrome being a classical example. These rare forms of obesity provide a unique source for identifying obesity-related genetic changes. Chromosomal microarray analysis (CMA) has allowed the characterization of new genetic forms of syndromic obesity, which are due to copy number variants (CNVs); however, CMA in large cohorts requires more study. The aim of this study was to characterize the CNVs detected by CMA in 279 patients with a syndromic obesity phenotype. RESULTS: Pathogenic CNVs were detected in 61 patients (22%) and, among them, 35 had overlapping/recurrent CNVs. Genomic imbalance disorders known to cause syndromic obesity were found in 8.2% of cases, most commonly deletions of 1p36, 2q37 and 17p11.2 (5.4%), and we also detected deletions at 1p21.3, 2p25.3, 6q16, 9q34, 16p11.2 distal and proximal, as well as an unbalanced translocation resulting in duplication of the GNB3 gene responsible for a syndromic for of childhood obesity. Deletions of 9p terminal and 22q11.2 proximal/distal were found in 1% and 3% of cases, respectively. They thus emerge as being new putative obesity-susceptibility loci. We found additional CNVs in our study that overlapped with CNVs previously reported in cases of syndromic obesity, including a new case of 13q34 deletion (CHAMP1), bringing to 7 the number of patients in whom such defects have been described in association with obesity. Our findings implicate many genes previously associated with obesity (e.g. PTBP2, TMEM18, MYT1L, POU3F2, SIM1, SH2B1), and also identified other potentially relevant candidates including TAS1R3, ALOX5AP, and GAS6. CONCLUSION: Understanding the genetics of obesity has proven difficult, and considerable insight has been obtained from the study of genomic disorders with obesity associated as part of the phenotype. In our study, CNVs known to be causal for syndromic obesity were detected in 8.2% of patients, but we provide evidence for a genetic basis of obesity in as many as 14% of cases. Overall, our results underscore the genetic heterogeneity in syndromic forms of obesity, which imposes a substantial challenge for diagnosis.

Atitudes dos professores de ensino fundamental e médio frente ao uso de substâncias psicoativas* / Attitudes of teachers of elementary and middle school towards the use psychoactive substances / Actitudes de los profesores de enseñanza fundamental y medio frente al uso de sustancias psicoactivas

O objetivo do estudo foi avaliar as atitudes dos professores de Ensino Fundamental e/ou Médio diante do uso de substâncias psicoativas, em sua função laboral. Trata-se de estudo descritivo e transversal. Participaram 75 professores de quatro instituições municipais e estaduais de dois municípios, que responderam um questionário contendo informações sociodemográficas e Drug and Drug Problems Perceptions Questionnaire. Utilizaram-se estatísticas descritivas e inferenciais para análise dos dados. Os resultados mostraram indiferença dos professores acerca do tema; aqueles que já haviam participado de capacitação tiveram atitudes mais negativas; os do sexo masculino, entretanto, atitudes mais positivas. Concluiu-se que tais atitudes evidenciam emergência de ações coletivas, preventivas que vinculem saúde e educação.

The objective of this study was to evaluate the attitudes of primary and / or middle school teachers regarding the use of psychoactive substances in their work function. It is a descriptive and cross-sectional study. Participants were 75 teachers from four municipal and state institutions of two municipalities, who answered a questionnaire containing sociodemographic information and Drug and Drug Problems Perceptions Questionnaire. Descriptive and inferential statistics were used to analyze the data. The results showed teachers' indifference about the subject; Those who had already participated in training had more negative attitudes; The male, however, more positive attitudes. It was concluded that such attitudes evidence the emergence of collective, preventive actions that link health and education.

El objetivo del estudio fue evaluar las actitudes de los profesores de Enseñanza Fundamental y/o Medio frente al uso de sustancias psicoactivas en su función laboral. Se trata de un estudio descriptivo y transversal. Participaron 75 profesores de cuatro instituciones municipales y estatales de dos municipios, que respondieron un cuestionario que contenía informaciones sociodemográficas y Drug and Drug Problems Perceptions Questionnaire. Se utilizaron estadísticas descriptivas e inferenciales para el análisis de los datos. Los resultados mostraron indiferencia de los profesores acerca del tema; Los que ya habían participado en la capacitación tuvieron actitudes más negativas; Los varones, sin embargo, actitudes más positivas. Se concluyó que tales actitudes evidencian emergencia de acciones colectivas, preventivas que vinculan salud y educación.

Determining the frequency of morphological characteristics in a sample of Brazilian children / Determinação de frequência de características morfológicas em uma amostra de crianças brasileiras

Abstract Objective: To establish the frequency of 82 morphological features in a sample of Brazilian children (between 3 and 13 years old), to understand the influence of age, gender, and ethnicity. Methods: This was a cross-sectional study that evaluated 239 children with typical development (between 3 and 13 years old) regarding the presence of 82 morphological characteristics. A previously described protocol, based on the London Dysmorphology Database, was applied to evaluate the sample. This protocol was culturally adapted to Brazilian Portuguese. Results: The frequency of 82 morphological characteristics was established in the sample; of 82 characteristics, 50% were considered morphological anomalies (frequency less than 4%). At least 25% of the sample presented more than one minor morphological anomaly. Age was shown to influence the frequency of the following morphological characteristics: widow's peak, prominent antihelix, prominent upper lip, irregular or crowded teeth, and clinodactyly, but had no influence on the frequency of minor morphological anomalies. Gender influenced dysplastic ears and attached earlobe, but had no influence on the frequency of minor morphological anomalies; ethnicity showed influence on camptodactyly and prominent antihelix. A statistically significant divergence was observed regarding 43 of the 73 morphological characteristics that could be compared with literature data (58.9%). Conclusions: The study determined the frequency of 82 morphological characteristics in 239 children with typical development. Age was the variable that showed more influence on the frequency of morphological characteristics, and comparison with literature data showed that the frequency depends on variables such as age and ethnicity.

Resumo Objetivo: Estabelecer a frequência de 82 características morfológicas em uma amostra de crianças brasileiras (entre três e 13 anos), para entender a influência da idade, do sexo e da etnia. Métodos: Estudo transversal. Avaliamos 239 crianças com desenvolvimento típico (entre três e 13 anos), em relação à presença de 82 características morfológicas. Aplicamos um protocolo descrito anteriormente, baseado no London Dysmorphology Database, para avaliar nossa amostra. Esse protocolo foi culturalmente adaptado ao português do Brasil. Resultados: A frequência de 82 características morfológicas foi estabelecida em nossa amostra; de 82 características, 50% foram consideradas anomalias morfológicas (frequência inferior a 4%). Pelo menos 25% da nossa amostra apresentaram mais de uma anomalia morfológica menor. A idade mostrou influência na frequência das seguintes características morfológicas: "bico de viúva", "anti-hélice proeminente", "lábio superior proeminente", "dentes irregulares ou encavalados" e "clinodactilia", mas não teve influência na frequência de anomalias morfológicas menores. O sexo mostrou influência nas seguintes características: "orelhas displásicas" e "lóbulo da orelha aderente", mas não teve influência na frequência de anomalias morfológicas menores; a etnia mostrou influência na "camptodactilia" e "anti-hélice proeminente". Houve divergência (estatisticamente significativa) em 43 características morfológicas de 73 que pudemos comparar com os dados da literatura (58,9%). Conclusões: Estabelecemos a frequência de 82 características morfológicas em 239 crianças com desenvolvimento típico. A idade foi a variável que mostrou maior influência na frequência de características morfológicas e a comparação com dados da literatura mostrou que a frequência depende de variáveis como idade e etnia.

Determining the frequency of morphological characteristics in a sample of Brazilian children.

OBJECTIVE: To establish the frequency of 82 morphological features in a sample of Brazilian children (between 3 and 13 years old), to understand the influence of age, gender, and ethnicity. METHODS: This was a cross-sectional study that evaluated 239 children with typical development (between 3 and 13 years old) regarding the presence of 82 morphological characteristics. A previously described protocol, based on the London Dysmorphology Database, was applied to evaluate the sample. This protocol was culturally adapted to Brazilian Portuguese. RESULTS: The frequency of 82 morphological characteristics was established in the sample; of 82 characteristics, 50% were considered morphological anomalies (frequency less than 4%). At least 25% of the sample presented more than one minor morphological anomaly. Age was shown to influence the frequency of the following morphological characteristics: widow's peak, prominent antihelix, prominent upper lip, irregular or crowded teeth, and clinodactyly, but had no influence on the frequency of minor morphological anomalies. Gender influenced dysplastic ears and attached earlobe, but had no influence on the frequency of minor morphological anomalies; ethnicity showed influence on camptodactyly and prominent antihelix. A statistically significant divergence was observed regarding 43 of the 73 morphological characteristics that could be compared with literature data (58.9%). CONCLUSIONS: The study determined the frequency of 82 morphological characteristics in 239 children with typical development. Age was the variable that showed more influence on the frequency of morphological characteristics, and comparison with literature data showed that the frequency depends on variables such as age and ethnicity.

Novel frameshift variant in gene SALL4 causing Okihiro syndrome.

Okihiro syndrome, Duane-radial ray syndrome or acro-reno-ocular syndrome (OMIM #607323) are alternative denominations describing an extremely variable condition, characterized by several radial defects of the upper limbs associated with Duane anomaly. It is a rare autosomal dominant disorder determined by variants in the SALL4 gene which encodes a transcription factor with eight zinc finger motifs. Here we report a novel heterozygous frameshift variant, c.410dupG, present in a Brazilian family. The five affected individuals exhibit a broad spectrum of phenotypes, ranging from the severe one presented by the index case (grossly shortened and deformed forearm, markedly hypoplastic and appendicular thumb, malformed right foot and ear malformation), to the less conspicuous condition presented by his near relatives (usually only triphalangeal or hypoplastic thumbs, sometimes associated with ulnar deviation); Duane's anomaly, however, was not observed in any of the affected family members. The c.410dupG variant is predicted to result in the translation of a truncated protein with 180 amino acid residues, lacking seven of the eight zinc finger motifs, with the same size of the predicted products of the already reported c.496dupC variant, described in two unrelated cases. However, the phenotypes observed in the three families (the one here reported and other two with c.496dupC variant) are very different. The analysis of cases so far published does not permit to establish a clear or direct genotype-phenotype correlation, but the three more severe foot malformation cases are due to variants predicted to encode truncated proteins lacking seven ZFMs. This might indicate a possible correlation between foot malformation and reduced size of the protein, suggesting that the nonsense-mediated-decay mechanism might not be so effective as to eliminate all SALL4 variants harboring premature termination codons.