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Juvenile idiopathic arthritis is a heterogeneous group of diseases characterized by arthritis with poorly known causes, including monogenic disorders and multifactorial etiology. 22q11.2 proximal deletion syndrome is a multisystemic disease with over 180 manifestations already described. In this report, the authors describe a patient presenting with a short stature, neurodevelopmental delay, and dysmorphisms, who had an episode of polyarticular arthritis at the age of three years and eight months, resulting in severe joint limitations, and was later diagnosed with 22q11.2 deletion syndrome. Investigation through Whole Genome Sequencing revealed that he had no pathogenic or likely-pathogenic variants in both alleles of the MIF gene or in genes associated with monogenic arthritis (LACC1, LPIN2, MAFB, NFIL3, NOD2, PRG4, PRF1, STX11, TNFAIP3, TRHR, UNC13DI). However, the patient presented 41 risk polymorphisms for juvenile idiopathic arthritis. Thus, in the present case, arthritis seems coincidental to 22q11.2 deletion syndrome, probably caused by a multifactorial etiology. The association of the MIF gene in individuals previously described with juvenile idiopathic arthritis and 22q11.2 deletion seems unlikely since it is located in the distal and less-frequently deleted region of 22q11.2 deletion syndrome.
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Artrite Juvenil , Síndrome de DiGeorge , Sequenciamento Completo do Genoma , Humanos , Artrite Juvenil/genética , Masculino , Síndrome de DiGeorge/genética , Oxirredutases Intramoleculares/genética , Pré-Escolar , Fatores Inibidores da Migração de Macrófagos/genética , CriançaRESUMO
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.
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Objective: Several endocrine manifestations have been described in patients with 22q11 deletion syndrome, including growth retardation, hypoparathyroidism, and thyroid disorders. This study aimed to characterize these abnormalities in a Colombian retrospective cohort of children with this condition. Methods: A retrospective study comprising a cohort of children with 22q11 deletion syndrome in Medellín, Colombia followed up between 2011 and 2017 was conducted. Results: Thirty-seven patients with a confirmed diagnosis of 22q11 deletion syndrome were included. 37.8% had some endocrinopathy, the most frequent being hypoparathyroidism (21.6%), followed by hypothyroidism (13.5%), hyperthyroidism (2.7%) and growth hormone deficiency (2.7%). There was wide heterogeneity in the clinical presentation, with late onset of severe hypocalcemia associated with seizure or precipitated in postoperative cardiac surgery, which highlights the importance of continuous follow-up as indicated by the guidelines. Short stature was mainly related to nutritional factors. Growth monitoring is required with the use of syndrome-specific charts and careful monitoring of the growth rate. Conclusion: As previously reported, a significant proportion of patients with endocrine abnormalities were found in this cohort. This highlights that it is essential to carry out an adequate multidisciplinary follow-up, based on the specific clinical guidelines, in order to avoid serious complications such as convulsions due to hypocalcemia. It is important to track size with curves specific to the syndrome and analyze the growth rate.
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Síndrome da Deleção 22q11 , Nanismo Hipofisário , Doenças do Sistema Endócrino , Hipocalcemia , Hipoparatireoidismo , Humanos , Criança , Estudos Retrospectivos , Colômbia , Hipocalcemia/etiologia , Hipocalcemia/diagnóstico , Síndrome da Deleção 22q11/genética , Síndrome da Deleção 22q11/complicações , Síndrome da Deleção 22q11/diagnóstico , Deleção CromossômicaRESUMO
DiGeorge syndrome is a disorder caused by a microdeletion on the long arm of chromosome 22. Approximately 1% of patients diagnosed with DiGeorge syndrome may have an absence of a functional thymus, which characterizes the complete form of the syndrome. These patients require urgent treatment to reconstitute T cell immunity. Thymus transplantation is a promising investigational procedure for reconstitution of thymic function in infants with congenital athymia. Here, we demonstrate a possible optimization of the preparation of thymus slices for transplantation through prior depletion of thymocytes and leukocyte cell lineages followed by cryopreservation with cryoprotective media (5% dextran FP 40, 5% Me2SO, and 5% FBS) while preserving tissue architecture. Thymus fragments were stored in liquid nitrogen at -196°C for 30 days or one year. The tissue architecture of the fragments was preserved, including the distinction between medullary thymic epithelial cells (TECs), cortical TECs, and Hassall bodies. Moreover, depleted thymus fragments cryopreserved for one year were recolonized by intrathymic injections of 3×106 thymocytes per mL, demonstrating the capability of these fragments to support T cell development. Thus, this technique opens up the possibility of freezing and storing large volumes of thymus tissue for immediate transplantation into patients with DiGeorge syndrome or atypical (Omenn-like) phenotype.
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BACKGROUND: Cognitive dysfunctions are frequently found in the 22q11.2 Deletion Syndrome, being an aggravating factor in the impairment of social relationships and communication, strongly impacting the functionality of the individual. Increasing the knowledge regarding cognitive skills may provide contributions to the diagnostic process and the intervention planning. OBJECTIVES: To estimate the general, verbal, and non-verbal cognitive functioning of children and adolescents with 22q11.2 Deletion Syndrome. METHODS: This is a cross-sectional, descriptive, and case series study regarding 15 individuals between 7-18 years-old diagnosed with 22q11.2 Deletion Syndrome. An assessment of the cognitive functions was performed using the Wechsler Abbreviated Scale of Intelligence (WASI). For data analysis we used a descriptive statistics analysis, having absolute frequencies for variables, and mean, median, standard deviation, minimum and maximum values for numerical variables. RESULTS: In the group analysis, we observed an important cognitive impairment degree. Most of the sampling (n=8; 53.33%) presented a considerably low total intelligence quotient score. Cases showing lower performances also presented greater difficulties regarding Visual Motor and Visuospatial coordination. Regarding the intelligence quotient representative punctuation in the WASI scale, the sample showed a large variability in the results (between 40 and 92 points), with the median total of 83. CONCLUSIONS: We observed important dysfunctions, cognitive difficulties, and intellectual, verbal, and non-verbal disabilities in the population studied. These findings indicate the need for an early intervention to assist not only the cognitive aspect, but also the socio-emotional development of children with the 22q11.2 Deletion Syndrome, aiming at their participation in society.
FUNDAMENTO: Disfunções cognitivas são frequentemente encontradas na Síndrome de Deleção 22q11.2, sendo um agravante no comprometimento das relações sociais e da comunicação, impactando fortemente na funcionalidade do indivíduo. O aumento do conhecimento sobre as habilidades cognitivas pode trazer contribuições no processo diagnóstico e no planejamento da intervenção. OBJETIVO: Estimar o funcionamento cognitivo geral, verbal e não verbal de crianças e adolescentes com Síndrome de Deleção 22q11.2. MÉTODOS: Estudo transversal, descritivo, tipo série de casos, com 15 indivíduos entre 7-18 anos com diagnóstico da Síndrome de Deleção 22q11.2. A avaliação das habilidades cognitivas foi realizada com a Escala Wechsler Abreviada de Inteligência (WASI). Para análise dos dados, foi utilizada análise estatística descritiva, com frequências absolutas para variáveis, e média, mediana, desvio padrão, mínima e máximo para variáveis numéricas. RESULTADOS: Na análise do grupo, observou-se um importante grau de comprometimento cognitivo. A maior parte da amostra (n=8; 53,33%) mostrou quociente de inteligência total extremamente baixo. Os casos com desempenhos mais baixos apresentaram maiores dificuldades em relação às habilidades de coordenação visuomotora e visuoespacial. Em relação à pontuação representativa do quociente de inteligência na escala WASI, a amostra apresentou uma grande variabilidade de resultados (entre 40 a 92 pontos), com mediana total de 83 pontos. CONCLUSÕES: As dificuldades cognitivas encontradas indicam a necessidade de uma intervenção precoce para auxiliar não só no desenvolvimento cognitivo, mas socioemocional de crianças com a Síndrome de Deleção 22q11.2 visando sua participação na sociedade.
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Humanos , Criança , Adolescente , Síndrome de DiGeorge/complicações , Síndrome de DiGeorge/diagnóstico , Disfunção Cognitiva , Testes de Inteligência , Escalas de Wechsler , Estudos Transversais , Deficiência Intelectual/diagnósticoRESUMO
BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is a rare disease with an important characteristic-clinical heterogeneity. The diversity of organs, regions, and systems of the body that can be affected requires periodic updating of health professionals so that they can recognize these clinical signs as belonging to 22q11.2DS. Updated professionals are equally important for the appropriate and timely clinical management of individuals with a positive diagnosis. In this context, this article aimed to map and analyze the access to healthcare for individuals with 22q11.2DS until the moment of diagnosis. RESULTS: We analyzed the clinical data of 111 individuals with 22q11.2DS registered in the Brazilian Database on Craniofacial Anomalies (BDCA) from 2008 to 2020. In this study, individuals were diagnosed at a median age of 9 years (mean = 9.7 years). Before the genetic investigation, they accessed 68.75% of the internationally recommended evaluations available at BDCA. Recurrent 22q11.2DS clinical manifestations such as delayed neuropsychomotor development, lip and/or palate defects, cardiac malformation and/or hematological/immunological alteration co-occurred in at least 72.06% of individuals. Cardiac malformation was the only clinical alteration that lowered the median diagnostic age, corresponding to 6.5 years of age with a cardiac malformation versus 11 years of age without one (p = 0.0006). CONCLUSIONS: In Brazil, 22q11.2 DS is under-recognized, and early diagnosis and management of affected individuals are still a distant reality. In this sense, 22q11.2 DS suspicion followed by the elimination of obstacles for its diagnosis confirmation is essential to increase life expectancy and improve the quality of life of these individuals in Brazil.
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Síndrome de DiGeorge , Cardiopatias Congênitas , Brasil , Criança , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Cardiopatias Congênitas/genética , Humanos , Qualidade de VidaRESUMO
Resumo Fundamento Algumas síndromes têm características específicas e facilmente reconhecíveis, enquanto outras podem ser mais complexas de se identificar e podem apresentar diferentes manifestações fenotípicas, por exemplo. Um diagnóstico etiológico é importante para entender a natureza da doença, para estabelecer o prognóstico e para começar o tratamento, permitindo a inclusão de pacientes na sociedade e reduzindo o custo financeiro dessas doenças. Objetivo A proposta inicial deste estudo foi a triagem citogenética para detectar a síndrome de deleção 22q11.2 (SD22q11.2) em recém-nascidos e crianças com doença cardíaca congênita utilizando a técnica da amplificação multiplex de sondas dependente de ligação (MLPA). Assim, por meio da pesquisa, outras mudanças genômicas foram identificadas nesses pacientes cardíacos. Nosso objetivo se estendeu a investigar essas outras mudanças citogenéticas. Métodos Investigamos 118 recém-nascidos com doenças cardíacas congênitas nascidos consecutivamente durante um ano, utilizando a técnica da MLPA. Resultados A técnica da MLPA permitiu a detecção da SD22q11.2 em 10/118 pacientes (8,5%). Outras alterações genômicas foram identificadas em 6/118 pacientes (5%): 1p36 del, 8p23 del (2 casos), 7q dup, 12 dup e 8q24 dup. Conclusão Este estudo ressalta a relevância da detecção de alterações genômicas que estão presentes em recém-nascidos e crianças com doenças cardíacas congênitas por meio de ferramentas citogenômicas.
Abstract Background Some syndromes have specific and easily recognizable features, while others may be more complex to identify and may present different phenotypic manifestations, for example. An etiological diagnosis is important to understand the nature of the disease, to establish the prognosis and to start the treatment, allowing the inclusion of patients in society and reducing the financial cost of such diseases. Objective The initial proposal of this study was cytogenetic screening for the detection of the 22q11.2 deletion syndrome in consecutive newborns and infants with congenital heart disease using the multiplex ligation-dependent probe amplification (MLPA) technique. Therefore, throughout our research, other genomic alterations were identified in these cardiac patients. Thus, our objective was extended to investigate these other cytogenetic alterations. Methods We investigated 118 neonates with congenital heart diseases born consecutively during one year using the MLPA technique. Results The MLPA technique allowed the detection of 22q11.2DS in 10/118 patients (8.5%). Other genomic alterations were also identified in 6/118 patients (5%): 1p36 del, 8p23 del (2 cases), 7q dup, 12 dup and 8q24 dup. Conclusion This study highlights the relevance of detecting genomic alterations that are present in newborns and infants with congenital cardiac diseases using cytogenomic tools.
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Humanos , Recém-Nascido , Lactente , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Brasil , Programas de Rastreamento , Deleção Cromossômica , Reação em Cadeia da Polimerase Multiplex/métodosRESUMO
OBJECTIVES: To evaluate various clinical aspects, specifically regarding immune status, in a large cohort of patients with DiGeorge syndrome. STUDY DESIGN: Data were collected for 98 patients with DiGeorge syndrome treated at a tertiary medical center. This included general information, laboratory results, and clinical features. RESULTS: The median age at diagnosis was 2.0 years (range, 0.0-36.5 years). The most common symptoms that led to diagnosis were congenital heart defect, speech delay, palate anomalies, and developmental delay. Common clinical features included recurrent infections (76 patients), congenital heart diseases (61 patients), and otorhinolaryngology disorders (61 patients). Twenty patients had anemia; the incidence was relatively high among patients aged 6-59 months. Thrombocytopenia was present in 20 patients. Recurrent chest infections were significantly higher in patients with T cell and T cell subset deficiencies. Decreased T cell receptor excision circles were more common with increasing age (P < .001). Of the 27 patients hospitalized due to infection, pneumonia was a leading cause in 13. CONCLUSIONS: Awareness of DiGeorge syndrome's typical and uncommon characteristics is important to improve diagnosis, treatment, surveillance, and follow-up.
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Síndrome de DiGeorge/fisiopatologia , Anormalidades Múltiplas/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Síndrome de DiGeorge/complicações , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: DiGeorge syndrome (DG) is a genetic disorder associated with 22q11 deletion. It involves various phenotypes, including craniofacial abnormalities, congenital heart disorders, endocrine dysfunction, cognitive deficits, and psychiatric disorders. Cases commonly involve multiple anomalies. However, little is known about the condition of the oral cavity in this disorder, although palate fissure, abnormal mandible, malocclusion, and tooth hypoplasia have been identified. We aimed to determine the odontological features of patients with 22q11.2 microdeletion, in relation to gingival health and oral hygiene. We report the systemic manifestations of nine patients and results of oral evaluation of two patients. In the oral examination, oral hygiene and gingivitis were evaluated. CASE PRESENTATION: In terms of the systemic manifestations, we found high frequencies of low weight and height at birth. In terms of the oral manifestations, both examined patients presented malocclusion, enamel hypoplasia, dental crowding, anodontia, and healthy periodontium. CONCLUSION: Although DG has been documented to involve periodontium disease, the patients in this study exhibited more dental manifestations such as enamel defects, misalignment between the teeth and the two dental arches, anodontia, and dental crowding. As such, a multidisciplinary approach combining dentistry and healthcare is recommended in this case.
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INTRODUCCIÓN. La deleción 22q11.2 es una alteración cromosómica muy frecuente, en la cual un 60% de los afectados presenta patologías neuropsiquiátricas. Determinar si existe asociación entre el síndrome de deleción 22q11.2 (SD22q11.2) y patologías como la esquizofrenia (EQZ), ofrece una oportunidad para la intervención temprana, y seguimiento de personas con este síndrome. OBJETIVO. El objetivo del presente trabajo es determinar si existe mayor riesgo de EQZ en pacientes con síndrome deleción 22q11.2. MÉTODOS. Se realizó una búsqueda bibliográfica sistemática de publicaciones con fecha de 1990 a 2020. Las búsquedas se realizaron en PubMed y en la base de datos Cochrane. En total, se evaluaron 19 estudios, de los que se consideraron elegibles diez publicaciones para el análisis, lo que corresponde a 824 participantes. RESULTADOS. El riesgo de presentar EQZ en un individuo con SD22q11.2 es de 20-25%, en comparación al 1% de la población general. CONCLUSIONES. El riesgo para un individuo con SD22q11.2 de presentar EQZ se encuentra bien establecido. Considerar este riesgo podría ayudar a un adecuado seguimiento y una intervención temprana.
INTRODUCTION. 22q11.2 deletion syndrome is a very common chromosomal abnormality, in which 60% of those affected have neuropsychiatric disorders. Determining if there is an association between 22q11.2 deletion syndrome (22q11.2DS) and disorders such as schizophrenia (SCZ) offers an opportunity for early intervention and follow-up of people with this syndrome. OBJECTIVE. The objective of this study is to determine if there is a greater risk of SCZ in patients with 22q11.2 deletion syndrome. METHODS. A systematic review was performed for publications dated 1990 to 2020. The strategy was to search in PubMed and Cochrane databases for specific MeSH terms. In total, 19 studies were reviewed, of which 10 publications were eligible for analysis, corresponding to 824 participants. RESULTS. The risk of presenting SCZ in an individual with 22q11.2DS is 20-25%, compared to 1% in the general population.CONCLUSIONS. The risk of presenting SCZ in an individual with 22q11.2DS is well established. Considering this risk could help with adequate follow-up and early intervention.
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Humanos , Esquizofrenia/epidemiologia , Síndrome da Deleção 22q11/epidemiologia , Esquizofrenia/genética , Medição de Risco , Síndrome de DiGeorge/epidemiologiaRESUMO
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.
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Abstract Congenital heart defects are the most common birth defects and the leading cause of mortality in the first year of life. It is well known that the 22q11 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans and that congenial heart diseases (CHDs) are one of the most common phenotypic manifestations. However, it should be noted that the 22q11 deletion was also found in a significant number of patients with isolated CHD. The 22q11DS phenotype may include cardiovascular anomalies, palatal abnormalities, nasal voice, immune deficiency, endocrine dysfunctions, a varying degree of cognitive deficits and intellectual disabilities, velopharyngeal insufficiency, and characteristic craniofacial dysmorphism. This condition affects about 1 in 4,000 live births, making 22q11DS the most common microdeletion syndrome in humans. Here we describe the cases of three children who were referred to the clinical hospital center with the diagnosis of CHD, but with no direct signs of 22q11DS. Investigation of familial data led us to suspect that the mothers could be carriers of 22q11DS. The multiplex ligation-dependent probe amplification (MLPA) testing confirmed that the patients and mothers exhibited 3 Mb 22q11 deletions, which justified the clinical signs in the mothers and the CHD in children. In the presence of a few characteristics that are common of a spectrum of some known syndromes, a familial examination can provide clues to a definitive diagnosis, as well as to the prevention of diseases and genetic counseling of these patients.
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Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Síndrome da Deleção 22q11/complicações , Cardiopatias Congênitas/genética , Fenótipo , Anormalidades Congênitas/genética , Insuficiência Velofaríngea , Síndrome de DiGeorge/genética , Aconselhamento GenéticoRESUMO
El síndrome de DiGeorge, también conocido como síndrome velocardiofacial o síndrome de deleción 22q11, se caracteriza por la ausencia congénita del timo y la glándula paratiroides. La tríada clásica de este trastorno es cardiopatía congénita, endocrinopatía con hipocalcemia e inmunodeficiencia primaria. Sin embargo, el síndrome puede exhibir múltiples alteraciones y manifestaciones clínicas pleiotrópicas que, a menudo, resultan en dismorfismo facial y alteraciones en el paladar. Clínicamente se evidencia mayor susceptibilidad a infecciones respiratorias o gastrointestinales recurrentes y, en los casos de aplasia tímica, se requiere tratamiento con antibióticos profilácticos y trasplante tímico, mientras que en los demás se hace manejo expectante. En este manuscrito se presenta el caso de un paciente masculino de 18 meses de edad, remitido al servicio de genética por presentar diversas alteraciones fenotípicas. Se describe el proceso mediante el cual se llegó al diagnóstico de síndrome de DiGeorge, a su manejo y pronóstico, y se hace una breve revisión de la literatura
DiGeorge syndrome, also known as velocardiofacial syndrome or 22q11 deletion syndrome, is characterized by the congenital absence of the thymus and the parathyroid gland. The classic triad of this disorder is congenital heart disease, endocrinopathy with hypocalcemia and primary immunodeficiency. However, the syndrome may exhibit multiple pleotropic abnormalities and clinical manifestations that often result in facial dysmorphism and changes in the palate. Clinically, a high susceptibility to recurrent respiratory or gastrointestinal infections is observed. In cases of thymic aplasia, treatment with prophylactic antibiotics and thymic transplantation is necessary, while in others, expectant management is used. This manuscript presents the case of an 18-month old male patient, referred to the genetics service due to several phenotypic alterations. The process by which the Di- George syndrome diagnosis, management and prognosis was reached, as well as a brief review of the literature, are presented.
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Humanos , Síndrome de DiGeorge , Relatos de Casos , Síndrome da Deleção 22q11RESUMO
ABSTRACT Purpose: The aim of this study was to identify the most typical and relevant categories of the International Classification of Functioning, Disability and Health (ICF) for patients with 22q11.2 Deletion Syndrome. Methods: Based on the Delphi technique an expert survey through e-mail was performed among health professionals' specialists in the 22q11.2DS. Data were collected in 2 rounds. Answers were analysed for the degree of consensus. Results: 7 Experts recruited through e-mail distribution lists of professional organizations and personal networks participated in the study. Categories in all ICF components that were considered typical and/or relevant by at least 80% of the responders were added to a pilot ICF instrument for children with 22q11.2DS, with a total of 145 ICF categories. Conclusion: a list of ICF categories that are considered relevant and typical for 22q11.2DS condition by international experts was created. This is an important step towards identifying ICF Core Sets for chronic paediatric conditions in Brazil.
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Humanos , Criança , Pessoas com Deficiência , Síndrome de DiGeorge , Brasil , Atividades Cotidianas , Exercício Físico , Classificação Internacional de Funcionalidade, Incapacidade e Saúde , Técnica Delphi , Avaliação da DeficiênciaRESUMO
El timo es un órgano cervicotorácico, impar y mediano, situado en la base del cuello y parte superior del mediastino. Junto a la médula ósea es uno de los dos órganos primarios del sistema inmune y ejerce su función en los neonatos y en los niños, fundamentalmente. Entra en regresión a partir de la pubertad, aunque algunos autores plantean que la involución puede comenzar un poco antes, cuando los principales tejidos linfoides están plenamente desarrollados. Interviene sinérgicamente con otras glándulas de secreción interna: tiroides, suprarrenal, hipófisis, para elaborar substancias necesarias para el desarrollo general del organismo. Es un órgano muy sensible a todo influjo. Como todos los órganos de la economía el timo presenta enfermedades producidas tanto por crecimiento exagerado, como por hipoplasias o atrofias. Dentro de las primeras las más comunes son la hiperplasia tímica y el timoma y, entre las últimas el síndrome de DiGeorge ha sido bien caracterizado en la literatura internacional desde la segunda mitad del siglo pasado. Sin embrago, en los últimos tiempos los inmunólogos hablan de la hipoplasia tímica como entidad que puede asociarse o no a estados de inmunodeficiencia. Se describen brevemente estas afecciones(AU)
The thymus is a cervicothoracic organ, odd and medium, located at the base of the neck and upper part of the mediastinum. Next to the bone marrow is one of the two primary organs of the immune system and exerts its function in neonates and children, fundamentally. It regresses after puberty, although some authors suggest that the involution can begin a little earlier, when the main lymphoid tissues are fully developed. It intervenes synergistically with other glands of internal secretion: thyroid, adrenal, pituitary gland, to develop substances necessary for the general development of the organism. It is a very sensitive organ to all influence. Like all the organs of the economy, the thymus presents diseases caused both by exaggerated growth, as by hypoplasias or atrophies. Among the former, the most common are thymic hyperplasia and thymoma and, among the latter, DiGeorge syndrome has been well characterized in international literature since the second half of the last century. However, in recent times immunologists speak of thymic hypoplasia as an entity that may or may not be associated with immunodeficiency states. These conditions are briefly described(AU)
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Humanos , Hiperplasia do Timo/complicações , Timo/fisiopatologia , Doenças Linfáticas/epidemiologiaRESUMO
BACKGROUND: Chromosome 22q11.2 microdeletion syndrome, a disorder caused by heterozygous loss of genetic material in chromosome region 22q11.2, has a broad range of clinical symptoms. The most common congenital anomalies involve the palate in 80% of patients, and the heart in 50-60% of them. The cause of the phenotypic variability is unknown. Patients usually harbor one of three common deletions sizes: 3, 2 and 1.5 Mb, between low copy repeats (LCR) designated A-D, A-C and A-B, respectively. This study aimed to analyze the association between these 3 deletion sizes and the presence of congenital cardiac and/or palatal malformations in individuals with this condition. A systematic review and meta-analysis were conducted, merging relevant published studies with data from Chilean patients to increase statistical power. RESULTS: Eight articles out of 432 were included; the data from these studies was merged with our own, achieving a total of 1514 and 487 patients to evaluate cardiac and palate malformations, respectively. None of the compared deleted chromosomal segments were statistically associated with cardiac defects (ORAB v/s AC-AD: 0.654 [0.408-1.046]; OR AD v/s AB-AC: 1.291 [0.860-1.939]) or palate anomalies (ORAB v/s AC-AD: 1.731 [0.708-4.234]; OR AD v/s AB-AC: 0.628 [0.286-1.382]). CONCLUSIONS: The lack of association between deletion size and CHD or PA found in this meta-analysis suggests that deletion size does not explain the incomplete penetrance of these 2 major manifestations, and that the critical region for the development of heart and palatal abnormalities is within LCR A-B, the smallest region of overlap among the three deletion sizes.
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Aracnodactilia/genética , Deleção Cromossômica , Craniossinostoses/genética , Síndrome de Marfan/genética , Humanos , FenótipoRESUMO
OBJECTIVE: Based on experiences and results from newborn screening for severe combined immunodeficiency (SCID), we evaluated the occurrence of chromosome 22q11.2 deletion syndrome (22q11.2DS) in newborns with different T cell receptor excision circles (TREC) results and established a second tier genetic test for 22q11.2DS. STUDY DESIGN: Recalled dried blood spots from 486 newborns with TREC results <90 copies/uL were tested from the SCID newborn screening. Quantitative real-time polymerase chain reaction assay was used to detect the copy number of TBX1 and HIRA genes by simple DNA extraction method. Multiplex ligation dependent probe amplification was used for further confirmation. RESULTS: Four hundred sixty-eight cases were considered negative because their haploid copy number of TBX1 and HIRA genes was >0.75. Eighteen cases with TBX1 and/or HIRA gene copy number <0.75 were suspected as positive, and 13 cases were further confirmed with 22q11.2DS. Detection rates of 22q11.2DS were 10.7% (6/56) in TREC <30 copies, 6.8% (9/132) in <50 TREC copies, 4.6% (12/260) in <70 TREC copies, and 2.7% (13/486) in <90 TREC copies. CONCLUSIONS: 22q11.2DS detection can be incorporated into the second-tier assay in subjects with low TREC copies in SCID screening. The dried blood spot methods were feasible for 22q11.2DS newborn screening.
Assuntos
Síndrome de DiGeorge/genética , Triagem Neonatal/métodos , Receptores de Antígenos de Linfócitos T/genética , Imunodeficiência Combinada Severa/genética , Proteínas de Ciclo Celular/genética , Síndrome de DiGeorge/complicações , Teste em Amostras de Sangue Seco/métodos , Feminino , Chaperonas de Histonas/genética , Humanos , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase Multiplex , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Imunodeficiência Combinada Severa/complicações , Proteínas com Domínio T/genética , Fatores de Transcrição/genéticaRESUMO
The 22q11.2 Deletion Syndrome (22q11.2DS), the most common human chromosome microdeletion syndrome, is associated with a very heterogeneous neurocognitive phenotype. One of the main characteristics of the syndrome spectrum is the intellectual variability, which encompasses average performance and intellectual disability and discrepancies between Verbal Intelligence Quotient and Performance Verbal Intelligence Quotient, with greater impairment in nonverbal tasks. The present study aimed at investigating the intellectual performance aspects of a 21children and adolescents sample from Brazil who had been diagnosed with 22q11.2DS, based on the Wechsler Intelligence Scale for Children - 4th edition. The samples were reviewed considering the differences between indices. The results revealed an Full Scale Intelligence Quotient predominant in the borderline range (42 to 104) and a significant discrepancy between the indices of Verbal Comprehension and Perceptual Reasoning in 42% of the sample. With regard to the performance in the subtests alone, a better performance was found in Similarities, whereas block design, matrix reasoning, digit span and letter-number sequencing subtests were the most challenging. These findings indicate that a comprehensive assessment of intellectual performance aspects covering the different measures of the Wechsler Intelligence Scale may contribute to a broader understanding of the neurocognitive phenotype associated with 22q11.2DS.
A Síndrome da Deleção 22q11.2 (SD22q11.2), microdeleção cromossômica mais frequente em humanos, é associada a um fenótipo neurocognitivo muito heterogêneo. Uma das principais características do espectro da síndrome é a variabilidade intelectual, que abrange de desempenho médio a deficiência intelectual, bem como discrepâncias entre Quociente de Inteligência Verbal e de Quociente de Inteligência de Execução, com maior prejuízo nas tarefas não verbais. O presente estudo teve por objetivo investigar aspectos do desempenho intelectual de uma amostra brasileira de 21 crianças e adolescentes diagnosticados com SD22q11.2, com base nos indicadores da Wechsler Intelligence Scale for Children - 4th edition. As amostras foram analisadas considerando diferenças entre os índices. Os resultados revelaram predomínio de Quociente de Inteligência Total na faixa limítrofe, entre 42 e 104, assim como discrepância significativa entre os índices de compreensão verbal e organização perceptual em 42% da amostra. No que concerne ao desempenho nos subtestes de forma isolada, um melhor resultado foi verificado em semelhanças, ao passo que cubos, raciocínio matricial, dígitos e sequência de números e letras foram os mais desafiadores. Esses achados indicam que uma avaliação abrangente de aspectos do desempenho intelectual contemplando as diversas medidas da Escala Wechsler de Inteligência pode contribuir para uma compreensão mais ampla do fenótipo neurocognitivo associado à SD22q11.2.
Assuntos
Escalas de Wechsler , Síndrome de DiGeorge , Genética Comportamental , NeuropsicologiaRESUMO
The syndrome produced by the deletion of chromosome 22q11 corresponds to a pattern of anomalies that occurs when a specific region of chromosome 22 is lost, specifically called 22q11.2. This microdeletion corresponds to the most frequent chromosomal alteration in humans, which has a prevalence of 1 per 4,000 live births. This includes a great variety of phenotypes, many of them subclinical, among which the Di George syndrome and the Velocardiofacial syndrome stand out. The main cause of mortality is of cardiac origin. Embryologically, this microdeletion is associated with alterations in the differentiation and migration of the pharyngeal system, with consequent craniofacial, cardiac, airway, thymus and parathyroid alterations, among others. In this sense, these patients present a higher risk of complications such as inmunodeficiency, hypocalcemia and hemorrhagic risk. From the surgical and anesthetic point of view, they can present cardiopathies of greater complexity of correction, which in some cases is also related to anatomical airway alterations which can constitute an important challenge when operating this type of patients. Considering the above, there is an increase in perioperative risk which could increase mortality. The objective of this review is to present the characteristics and behavior of this group of patients in the correction of their heart diseases, so that they are known by the anesthesiologists who work in the cardiovascular area.
El síndrome de microdeleción 22q11 corresponde a un patrón de anomalías que se produce al perderse una región específica del cromosoma 22, específicamente llamada 22q11.2. Esta microdeleción corresponde a la alteración genética más frecuente en humanos la cual tiene una prevalencia de 1 cada 4.000 recién nacidos vivos. Incluye una gran variedad de fenotipos, muchos de ellos subclínicos, entre los que destaca el síndrome Di George y el síndrome Velocardiofacial. La principal causa de mortalidad es de origen cardíaco. Embriológicamente la microdeleción se asocia a alteraciones en diferenciación y migración del aparato faríngeo, con las consiguientes alteraciones cráneo-faciales, cardíacas, de vía aérea, timo y paratiroides, entre otras. En ese sentido, presentan mayor frecuencia de complicaciones tales como infecciones, hipocalcemia y riesgo hemorrágico. Desde el punto de vista quirúrgico y anestésico pueden presentar cardiopatías de mayor complejidad de corrección, asociado o no a alteraciones anatómicas en vía aérea lo que puede constituir un importante desafío al momento de intervenir. Lo anterior aumenta el riesgo perioperatorio, lo que podría derivar en aumento de la mortalidad. El objetivo de esta revisión es presentar las características y comportamiento de este grupo de pacientes en la corrección de sus cardiopatías, de modo que sean un aporte para los anestesiólogos que se desempeñan en el área cardiovascular.
Assuntos
Humanos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Síndrome da Deleção 22q11/complicações , Cardiopatias Congênitas , Anestesia , Complicações Pós-Operatórias , Risco , Hospedeiro Imunocomprometido , Síndrome de DiGeorge , Síndrome da Deleção 22q11/diagnóstico , Síndrome da Deleção 22q11/fisiopatologia , Hemorragia , HipocalcemiaRESUMO
INTRODUCTION: Deletion 22q11.2 occurs in 1:4,000-1:6,000 live births while 10p13p14 deletion is found in 1:200,000 newborns. Both deletions have similar clinical features such as congenital heart disease and immunological anomalies. OBJECTIVE: We looked for a 22q11.2 deletion in Mexican patients with craniofacial dysmorphisms suggestive of DiGeorge or velocardiofacial syndromes and at least one major phenotypic feature (cardiac anomaly, immune deficiency, palatal defects or development delay). METHODS: A prospective study of 39 patients recruited in 2012-2015 at the Instituto Mexicano del Seguro Social at Guadalajara, Mexico. The patients with velocardiofacial syndrome-like features or a confirmed tetralogy of Fallot (TOF) or complex cardiopathy were studied by G-banding and fluorescence in situ hybridization (FISH) with a dual TUPLE1(HIRA)/ARSA or TUPLE1(22q11)/22q13(SHANK3) probe, six patients without the 22q11.2 deletion (arbitrarily selected) were tested with the dual DiGeorge II (10p14)/D10Z1 probe. RESULTS: Twenty-two patients (7 males and 15 females) had the 22q11.2 deletion and 17/39 did not have it; no patient had a 10p loss. Among the 22 deleted patients, 19 had congenital heart disease (mostly TOF). Twelve patients without deletion had heart defects such as TOF (4/12), isolate ventricular septal defect (2/12) or other disorders (6/12). CONCLUSION: In our small sample about ~56% of the patients, regardless of the clinical diagnosis, had the expected 22q11.2 deletion. We remark the importance of early cytogenetic diagnosis in order to achieve a proper integral management of the patients and their families.
INTRODUCCIÓN: La deleción 22q11.2 ocurre con una frecuencia de 1:4,000-1:6,000 nacidos vivos, mientras que la deleción 10p13p14 es detectada en 1:200,000 recién nacidos. Ambas deleciones comparten características clínicas similares tales como defectos cardiacos congénitos y anomalías inmunológicas. OBJETIVO: Identificar la deleción 22q11.2 en pacientes mexicanos con dismorfismo craneofacial sugestivo de síndrome DiGeorge o velocardiofacial y por lo menos con una característica clínica mayor (anomalía cardiaca, deficiencia inmunológica, defectos en paladar o retardo en el desarrollo). MÉTODOS: Estudio prospectivo de 39 pacientes captados entre 2012-2015 en el Instituto Mexicano del Seguro Social en Guadalajara, México. Los pacientes con características clínicas sugerentes de síndrome velocardiofacial o diagnostico confirmado de tetralogía de Fallot (TOF) o cardiopatía compleja fueron estudiados por bandas G y por hibridación in situ fluorescente (FISH) con una sonda dual TUPLE1(HIRA)/ARSA o TUPLE1(22q11)/22q13(SHANK3), seis pacientes sin la deleción 22q11.2 (seleccionados arbitrariamente) fueron estudiados con la sonda dual DiGeorge II (10p14)/D10Z1. RESULTADOS: Veintidós pacientes (7 hombres y 15 mujeres) tuvieron la deleción 22q11.2 y 17/39 no la tuvieron, ningún paciente tuvo la pérdida de 10p. Entre los 22 pacientes delecionados, 19 tuvieron defecto cardiaco congénito (principalmente TOF). Doce pacientes sin la deleción tuvieron defectos cardiacos congénitos como TOF (4/12), defecto del septo ventricular aislado (2/12) y otros trastornos cardiacos (6/12). CONCLUSIÓN: En nuestra pequeña muestra, alrededor de ~56% de los pacientes, independientemente de su diagnostico clínico, tuvieron la deleción 22q11.2 esperada. Resaltamos la importancia del diagnóstico citogenético temprano para determinar un apropiado manejo integral para el paciente y sus familiares.