Hospitalized patients with X-linked disease and infected with SARS-CoV-2 in Brazil: A serial case report from the first two years of the pandemic.

We described the characteristics of 18 patients with coronavirus disease (COVID)-19 and X-linked disorders in a cohort of 2,066,678 Brazilian patients hospitalized due to COVID-19. The patients were diagnosed with Hemophilia B (one patient), Klinefelter syndrome [eight patients- three deaths occurred, one unrelated to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection], and Turner syndrome (nine patients- two patients died). Half of the patients with X-linked disorders and COVID-19 (9/18) were male, the age varied from 1 to 71 years, and most patients were White (9/12; six patients had missing data). The most common symptoms were cough (13/17; one patient had missing data) and fever (12/16; two patients had missing data), whereas the most common comorbidities were diabetes mellitus (3/11; seven patients had missing data) and cardiopathy (2/12; six patients had missing data). Nearly half of the patients needed intensive care unit (8/17; one patient had missing data), and a quarter required invasive mechanical ventilation (4/16; two patients had missing data). Our study accounted for a total of five deaths, one unrelated to COVID-19. There may be several reasons for the low number of X-linked patients found in our data, such as limited access to genetic diagnosis tools causing underdiagnosis and a lack of knowledge by health professionals to identify the necessity of a genetic diagnosis or even forgetting to fill in the Brazilian database for hospitalization due to severe acute respiratory syndrome.

Clinical, cytogenetic, and genomic analyses of an Ecuadorian subject with Klinefelter syndrome, recessive hemophilia A, and 1;19 chromosomal translocation: a case report.

BACKGROUND: Hemophilia A is considered one of the most common severe hereditary disorders. It is an X-linked recessive disease caused by a deficiency or lack of function of the blood clotting factor VIII. Klinefelter syndrome is a genetic disorder that affects male individuals due to one or more extra X chromosomes, present in all cells or with mosaicism. The aneuploidy is due to either mitotic or meiotic chromosome non-disjunction. Chromosomal translocations are a group of genome abnormalities in which a region or regions of a chromosome break and are transferred to a nonhomologous chromosome or a new location in the same chromosome. CASE PRESENTATION: Our subject was born in Ecuador at 36 weeks of gestation by vaginal delivery. At 3 months old, the Factor VIII activity measure showed a 23.7% activity indicating a diagnosis of mild hemophilia A. At 1 year old, the karyotype showed an extra X chromosome, consistent with a diagnosis of Klinefelter syndrome, and a translocation between the long arms of chromosomes 1 and 19, at positions q25 and q13, respectively. CONCLUSIONS: Klinefelter syndrome and hemophilia are a rare combination. In the present case report, the subject presents both, meaning that he has inherited one X chromosome from the father and one X chromosome from the mother. Since the father has severe hemophilia A; and the subject presents a below 40% Factor VIII activity, a skewed X inactivation is suggested. Additionally, the proband presents a translocation with the karyotype 47,XXY,t(1;19)(q25;q13). No similar report with phenotypic consequences of the translocation was found. The present report highlights the importance of a correct diagnosis, based not only on the clinical manifestations of a disease but also on its genetic aspects, identifying the value of integrated diagnostics. The subject presents three different genetic alterations, Klinefelter syndrome, hemophilia A, and a 1;19 chromosomal translocation.

Educational status, testosterone replacement, and intelligence outcomes in Klinefelter syndrome.

Most male hypergonadotropic hypogonadism associated with infertility can be attributed to a single genetic condition such as Klinefelter syndrome (KS). This disease's wide phenotypic variability is frequently associated with mosaic 47,XXY lineages and testosterone replacement. Early diagnosis and treatment have been associated with better cognitive and intellectual outcomes, but the scope of this influence requires further investigation. Objective: This study aimed to investigate the intelligence profile of a cohort of patients with KS, considering the influence of educational level and clinical variables. Methods: Twenty-nine (9-65 years) individuals were submitted to the measures of intelligence quotient (IQ) (Wechsler's Scales) and adaptive behavior (Vineland-II). Linear regression analysis included the participants' educational level and clinical variables (i.e., comorbidities and use of testosterone) as predictors and intellectual performance and adaptive behavior as outcomes. Results: Scores varied from intellectual deficiency to average ranges (82.5+15.8). There were significant differences between adult's and children's IQ and between verbal and nonverbal indexes. The level of education predicted both IQ and adaptive behavior. Testosterone replacement therapy and absence of seizures predicted only adaptive behavior. Conclusions: The level of education and hormonal therapy can be selectively implicated in the intellectual variability in KS.

A maioria dos casos de hipogonadismo hipergonadotrófico masculino associado à infertilidade pode ser atribuída a uma única condição genética ­ a síndrome de Klinefelter (KS). A ampla variabilidade fenotípica dessa doença está frequentemente associada a linhagens de mosaico 47,XXY e também à reposição de testosterona. O diagnóstico e o tratamento precoces têm sido associados a melhores desfechos em termos de cognição e inteligência, mas o escopo dessa influência requer maior investigação. Objetivo: Este estudo investigou o perfil de inteligência de uma coorte de pacientes com KS, considerando a influência do nível educacional e das variáveis clínicas. Métodos: Vinte e nove indivíduos (9­65 anos) foram submetidos a medidas de quociente de inteligência (escalas Wechsler) e de comportamento adaptativo (escala Vineland-II). A análise de regressão linear considerou o nível educacional dos participantes e variáveis clínicas (comorbidades, uso de testosterona) como preditores e desempenho intelectual e comportamento adaptativo como desfechos. Resultados: Os resultados mostraram escores que variaram de deficiência intelectual à faixa média (82,5+15,8). Houve diferenças significativas entre os quocientes de inteligência de adultos e crianças e entre os índices verbais e não verbais. O nível educacional influenciou tanto o quociente de inteligência quanto o comportamento adaptativo. A terapia de reposição de testosterona e a ausência de convulsões influenciaram apenas o comportamento adaptativo. . Conclusões: Sendo assim, nível educacional e terapia hormonal podem estar seletivamente implicados na variabilidade intelectual na KS.

Recent advancement in the treatment of boys and adolescents with hypogonadism.

Clinical manifestations and the need for treatment varies according to age in males with hypogonadism. Early foetal-onset hypogonadism results in disorders of sex development (DSD) presenting with undervirilised genitalia whereas hypogonadism established later in foetal life presents with micropenis, cryptorchidism and/or micro-orchidism. After the period of neonatal activation of the gonadal axis has waned, the diagnosis of hypogonadism is challenging because androgen deficiency is not apparent until the age of puberty. Then, the differential diagnosis between constitutional delay of puberty and central hypogonadism may be difficult. During infancy and childhood, treatment is usually sought because of micropenis and/or cryptorchidism, whereas lack of pubertal development and relative short stature are the main complaints in teenagers. Testosterone therapy has been the standard, although off-label, in the vast majority of cases. However, more recently alternative therapies have been tested: aromatase inhibitors to induce the hypothalamic-pituitary-testicular axis in boys with constitutional delay of puberty and replacement with GnRH or gonadotrophins in those with central hypogonadism. Furthermore, follicle-stimulating hormone (FSH) priming prior to hCG or luteinizing hormone (LH) treatment seems effective to induce an enhanced testicular enlargement. Although the rationale for gonadotrophin or GnRH treatment is based on mimicking normal physiology, long-term results are still needed to assess their impact on adult fertility.

Clinical outcomes of 77 TESE treatment cycles in non-mosaic Klinefelter syndrome patients.

OBJECTIVE: The current study aimed to present the clinical outcomes of 76 azoospermic patients with non-mosaic Klinefelter syndrome (KS), treated with testicular spermatozoa extraction (TESE) followed by intracytoplasmic sperm injection (ICSI) using either fresh or cryopreserved testicular spermatozoa. METHODS: We retrospectively evaluated 76 patients with non-mosaic KS belonging to a special group of cases that besides infertility did not present the classical signs and symptoms of testosterone deficiency. One of the patients repeated the TESE procedure (76 patients, 77 TESE cycles). Sixty of these 76 patients accepted to undergo TESE associated with ovarian stimulation, while 16 patients underwent TESE followed by testicular spermatozoa cryopreservation. Aneuploidy screening of the offspring was performed by Multiplex ligation-dependent probe amplification and by amniotic fluid karyotyping. Statistical analysis used the Chi-Squared Test, Fisher's Exact Test, 2-sided, for rates, and the Independent Samples T-test for equality of means, 2-sided. RESULTS: Testicular spermatozoa were recovered in 31 (40.3%) of the attempts. The patients underwent 47 ICSI cycles, 25 with fresh testicular spermatozoa and 22 with cryopreserved testicular spermatozoa. Fertilization (63.5% vs. 41.6%, p=0.000), implantation (37% vs. 13.2%, p=0.014), clinical pregnancy (60.9% vs. 19%, p=0.005) and live birth (65.2% vs. 23.8%, p=0.006) rates were higher with fresh testicular spermatozoa. Chromosome analysis of the 21 newborns was normal. CONCLUSIONS: The present data adds further information regarding the recovery rate of spermatozoa after TESE and the embryological and clinical outcomes with fresh and cryopreserved testicular spermatozoa, besides reassuring the safety concerning chromosomal transmission of KS from parents to their offspring.

Intelligence Quotient Variability in Klinefelter Syndrome Is Associated With GTPBP6 Expression Under Regulation of X-Chromosome Inactivation Pattern.

Klinefelter syndrome (KS) displays a broad dysmorphological, endocrinological, and neuropsychological clinical spectrum. We hypothesized that the neurocognitive dysfunction present in KS relies on an imbalance in X-chromosome gene expression. Thus, the X-chromosome inactivation (XCI) pattern and neurocognitive X-linked gene expression were tested and correlated with intelligence quotient (IQ) scores. We evaluated 11 KS patients by (a) IQ assessment, (b) analyzing the XCI patterns using both HUMARA and ZDHHC15 gene assays, and (c) blood RT-qPCR to investigate seven X-linked genes related to neurocognitive development (GTPBP6, EIF2S3, ITM2A, HUWE1, KDM5C, GDI1, and VAMP7) and XIST in comparison with 14 (male and female) controls. Considering IQ 80 as the standard minimum reference, we verified that the variability in IQ scores in KS patients seemed to be associated with the XCI pattern. Seven individuals in the KS group presented a random X-inactivation (RXI) and lower average IQ than the four individuals who presented a skewed X-inactivation (SXI) pattern. The evaluation of gene expression showed higher GTPBP6 expression in KS patients with RXI than in controls (p = 0.0059). Interestingly, the expression of GTPBP6 in KS patients with SXI did not differ from that observed in controls. Therefore, our data suggest for the first time that GTPBP6 expression is negatively associated with full-scale IQ under the regulation of the type of XCI pattern. The SXI pattern may regulate GTPBP6 expression, thereby dampening the impairment in cognitive performance and playing a role in intelligence variability in individuals with KS, which warrants further mechanistic investigations.

Gene Copy Number Quantification of SHOX, VAMP7, and SRY for the Detection of Sex Chromosome Aneuploidies in Neonates.

Aims: To explore the feasibility of detecting sex chromosome aneuploidies (SCAs) by means of gene copy number quantification of short stature homeobox (SHOX), vesicle-associated membrane protein 7 (VAMP7), and SRY in newborns. Materials and Methods: Gene doses of SHOX, VAMP7, and SRY were determined by quantitative polymerase chain reaction (qPCR) using DNA obtained from dried blood samples from newborns. Relative quantification values were obtained. An aneuploidy profile was established according to cutoff values. Samples with ≥2 gene doses (out of range) were reanalyzed, and those with aneuploidy profiles were confirmed by karyotyping. Sensitivity, specificity, and positive and negative predictive values were obtained. Results: A total of 10,033 samples were collected (4945 females and 5088 males). Of 244 (2.43%) samples with ≥2 gene doses that were retested, 20 cases were confirmed. The overall incidence of SCAs was 1 in 500 live newborns. There were six cases of Turner syndrome (1/824), 3 cases of XXX (1/1648), 7 cases of Klinefelter syndrome (1/726), and 4 cases of of XYY (1/1272). The sensitivity was 0.952 (95.42%); the specificity was 0.975 (97.56%); the positive predictive value was 0.909 (90.91%) and the negative predictive value was 0.987 (98.77%). Conclusions: Gene copy number analyses of the VAMP7, SHOX, and SRY genes by qPCR from blood samples spotted onto filter paper is a highly reliable method for the early detection of male and female SCAs.

Androgen Treatment in Adolescent Males With Hypogonadism.

During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass. Testosterone is the most abundant testicular androgen, but some effects are mediated by its conversion to the more potent androgen dihydrotestosterone (DHT) or to estradiol. Androgen deficiency, requiring replacement therapy, may occur due to a primary testicular failure or secondary to a hypothalamic-pituitary disorder. A very frequent condition characterized by a late activation of the gonadal axis that may also need androgen treatment is constitutional delay of puberty. Of the several testosterone or DHT formulations commercially available, very few are employed, and none is marketed for its use in adolescents. The most frequently used androgen therapy is based on the intramuscular administration of testosterone enanthate or cypionate every 3 to 4 weeks, with initially low doses. These are progressively increased during several months or years, in order to mimic the physiology of puberty, until adult doses are attained. Scarce experience exists with oral or transdermal formulations. Preparations containing DHT, which are not widely available, are preferred in specific conditions. Oxandrolone, a non-aromatizable drug with higher anabolic than androgenic effects, has been used in adolescents with preserved testosterone production, like Klinefelter syndrome, with positive effects on cardiometabolic health and visual, motor, and psychosocial functions. The usual protocols applied for androgen therapy in boys and adolescents are discussed.

Malformación genital: disparador del diagnóstico de variantes severas de síndrome de Klinefelter / Genital malformation: trigger of the diagnosis of severe variants of Klinefelter syndrome

Resumen: Introducción: El síndrome de Klinefelter y sus variantes, como alteración en el número de cromosomas sexuales, se encuentra entre los trastornos del desarrollo sexual. Sus portadores manifiestan hipogonadismo hipergonadotrófico en la pubertad; las variantes severas presentan además problemas neurocognitivos y del lenguaje desde edades tempranas. Objetivo: Describir dos pacientes portadores de mal formación genital con diagnóstico genético de variantes severas de síndrome de Klinefelter; y revisar aspectos clínicos y terapéuticos. Casos Clínicos: Caso 1: Diagnóstico de genitales atípicos al nacer: Falo pequeño y corvo con meato uretral a nivel escrotal y escroto bífido. Sin otra anomalía somática, excepto sutil clinodactilia del 5 dedo. Cariotipo: 49,XXXXY. Al año de vida se reconstruyeron los genitales. Evolucionó con retraso global del desarrollo, principalmente del lenguaje, manejado con estimulación temprana kinésica y fonoaudiológica desde los 2 meses, logró integrarse en un jardín de infantes. Caso 2: Al mes de vida se constató falo pequeño y corvo severo (más de 70°), testículos en bolsa. Cariotipo: 48,XXYY. Al año de vida se corrigió malformación del pene. Evolucionó con retraso global del desarrollo, fundamentalmente en el lenguaje expresivo, y fue manejado con el equipo de estimulación temprana desde los 4 meses, logrando adaptación en un jardín de infantes. Conclusión: Las malformaciones genitales condujeron al diagnóstico de variantes severas de síndrome de Klin efelter, y fueron corregidas alrededor del año de vida. La identificación temprana de estas variantes permitió la intervención del equipo de neuroestimulación, favoreciendo el desarrollo neurocognitivo y la integración social de estos niños.

Abstract: Introduction: Among the disorders of sexual development, Klinefelter syndrome and its variants are classified as an alteration in the number of sex chromosomes. These patients show signs of hypergonadotropic hypogonadism at puberty, however cases of severe variants also present neurocognitive and language problems from an early age. Objective: To describe two patients with genital malformation with genetic diagnosis of severe variants of Klinefelter syndrome, and to review clinical and therapeutic aspects. Clinical Cases: Case 1: Diagnosis of atypical genitalia at birth: Small and curved phallus with the urethral meatus at scrotal level, and bifid scrotum. No other somatic abnormality was observed, except for subtle clinodactyly of the fifth finger. Karyotype: 49, XXXXY. At one year of life, genitalia were reconstructed. The patient presented a global developmental delay, mainly in language, which was managed with early stimulation and speech and language therapy since he was two months old. Finally, he was able to attend kindergarten. Case 2: At one month of life, a small and severe curved phallus (more than 70°) was observed, and testicles were in the scrotum. Karyotype: 48, XXYY. At one year of life, the penile malformation was corrected. The patient presented global developmental delay, mainly in expressive language which was managed with early stimulation since the age of four months, achieving kindergarten attendance. Conclusion: Genital malformations led to the diagno sis of severe variants of Klinefelter syndrome, and were corrected around the year of life. The early identification of these variants allowed the intervention of the neurostimulation team, favoring the neurocognitive development and social integration of these children.

Association between Down Syndrome and Disorders of Sex Development: Report of Three Cases and Review of 188 Cases in the Literature.

In this study, we present 3 cases of Down syndrome (DS) associated with disorders/differences of sex development (DSD) and review the literature on this topic. Case 1: 1-year-old child with male genitalia and DS phenotype, 47,XX,+21 karyotype and testicular DSD. Case 2: 11-month-old child with male genitalia and few DS dysmorphisms, 45,X/47,XY,+21 karyotype, and mixed gonadal dysgenesis. Case 3: 4-month-old child with female genitalia and DS phenotype, 47,XY,+21 karyotype and XY complete gonadal dysgenesis. In the literature, among 188 patients, 107 (57%) had Klinefelter syndrome and 61 (33%) Turner syndrome, 12 (6%) had mixed gonadal dysgenesis, 2 (1%) had partial androgen insensitivity, 2 (1%) ovotesticular DSD, and the others had congenital adrenal hyperplasia, XY partial gonadal dysgenesis, XY complete gonadal dysgenesis, and complete androgen insensitivity (1 case each). A typical DS phenotype was found in all individuals of the revision, with the exception of one case, but DSD features were not always reported. In conclusion, the association of DS with sex chromosome DSD is the most frequently observed, whereas associations with 46,XX and 46,XY DSD is extremely rare.

Cuidado de enfermería postoperación de Tromboendarterectomia Pulmonar Bilateral. Estudio de caso fundamentado en los principios de Henderson / Nursing care after Bilateral Pulmonary Thromboendarterectomy. Case study based on Henderson's principles / Cuidados de enfermagem após tromboendarterectomia pulmonar bilateral. Estudo de caso baseado nos princípios de Henderson

Resumen Introducción La tromboembolia pulmonar (TEP) es un padecimiento que se presenta con frecuencia de manera silenciosa, el 50 % o más de los casos no se diagnostica. Se define como la oclusión total o parcial de la circulación pulmonar, ocasionada por un coágulo sanguíneo proveniente de la circulación venosa sistémica, incluidas las cavidades derechas y que, de acuerdo a su magnitud, puede o no originar síntomas. Está considerada como una urgencia cardiovascular y constituye una de las principales causas de morbimortalidad en pacientes hospitalizados. Objetivo Desarrollar un Estudio de caso basado en el Proceso de Atención de Enfermería en la persona postoperada de Tromboendarterectomía Pulmonar Bilateral en Unidad de cuidados intensivos postquirúrgica de un Instituto Nacional de Tercer Nivel de la Ciudad de México. Método Estudio de caso basado en las etapas del proceso enfermero, se utilizó una Guía de valoración de las 14 necesidades de Virginia Henderson, jerarquización de Diagnósticos enfermeros, se ofreció una atención integral enfocada en cuidados especializados para cubrir las necesidades más afectadas en la persona. Conclusiones La aplicación del proceso de atención enfermero con base en la valoración de las 14 necesidades de Virginia Henderson, identificó que las necesidades más afectadas fueron; Oxigenación/Circulación y Evitar peligros, con la jerarquización se determinó que es imprescindible el conocimiento de enfermería en intervenciones especificas en el proceso postoperatorio de Tromboendarterectomía como: la detección del riesgo de alteraciones del ritmo cardiaco, valoración e intervenciones en insuficiencia respiratoria aguda, la propensión a eventos trombóticos secundarios a afección genética, para el logro de la recuperación de la salud de manera exitosa.

Abstract Introduction Since a pulmonary embolism (PE) can develop silently, more than 50 % of cases are not diagnosed until clear signs and symptoms are present. It is defined as the partial or total blockage of pulmonary circulation due to a blood clot which originated from the venous circulation elsewhere. Considered a cardiovascular urgency, it is a main cause of morbidity and mortality among hospitalized patients. Objective Based on the Nursing Process, to carry out a study case on a person who underwent surgery for Bilateral Pulmonary Thromboendarterectomy in the ICU of a Third Level of Care National Institute of Mexico City. Method This is a study case which followed the stages of the Nursing Process. An assessment guide of the 14 needs proposed by Virginia Henderson was utilized. Nursing diagnoses were ranked. An integral and specialized care addressing the patient's most important needs was offered. Conclusions The most important needs identified were: promoting oxygenation and circulation, and preventing risks. From the diagnoses analysis, it was determined that nursing knowledge is crucial in post thromboendarterectomy interventions, in terms of heart rate alteration risk detection, acute respiratory insufficiency assessment, and secondary thrombotic events prevention, all these in order to achieve a successful recovery.

Resumo Introdução A trombo embolia pulmonar (TEP) é uma doença que se apresenta com frequência de maneira silenciosa, o 50 % ou mais dos casos não se diagnostica. Define-se como a oclusão total ou parcial da circulação pulmonar, ocasionada por um coágulo sanguíneo proveniente da circulação venosa sistémica, incluídas as cavidades direitas e que, conforme sua magnitude, pode ou não originar sintomas. É considerada como uma urgência cardiovascular e constitui uma das principais causas de morbimortalidade em pacientes hospitalizados. Objetivo Desenvolver um Estudo de caso baseado no Processo de Atenção de Enfermagem na pessoa pós-perada de Tromboendarterectomia Pulmonar Bilateral na Unidade de cuidados intensivos post-cirúrgica de um Instituto Nacional de Terceiro Nível da Cidade do México. Método Estudo de Caso baseado nas etapas do processo enfermeiro, utilizou-se uma Guia de avaliação das 14 necessidades de Virginia Henderson, hierarquização de Diagnósticos enfermeiros, ofereceu-se uma atenção integral focalizada em cuidados especializados para cobrir as necessidades mais afetadas na pessoa. Conclusões A aplicação do processo de atenção enfermeiro com base na avaliação das 14 necessidades de Virginia Henderson, identificou que as necessidades mais afetadas foram; Oxigenação/Circulação e Evitar perigos, com a hierarquização determinou-se que é imprescindível o conhecimento de enfermagem em intervenções especificas no processo pós-operatório de Tromboendarterectomia como: a detecção do risco de alterações do ritmo cardíaco, avaliação e intervenções em insuficiência respiratória aguda, a propensão a eventos trombóticos secundários a afecção genética, para o sucesso da recuperação da saúde de maneira bem-sucedida.

Síndrome de Klinefelter diagnosticado en un adulto a raíz del estudio de infección respiratoria recurrente y masa mediastínica: caso clínico / Thymoma in a patient with klinefelter syndrome: case report

Klinefelter syndrome (47, XXY in most cases) is a frequently underdiagnosed chromosomal anomaly associated with multiple comorbidities in adult life. Patients with Klinefelter syndrome have a higher risk of cancer. Specifically, these patients have a higher risk for mediastinal germ cell tumors. It is estimated that 8% of male patients with mediastinal tumors have Klinefelter. We report a 42-years-old male who suffered recurrent respiratory infections. During the study, a mediastinal mass was found, whose pathological study disclosed a type B thymoma. The patient had a history of infertility, high stature, gynecomastia, obesity with gynecoid distribution of body fat and testicular atrophy. A karyotype was requested (47, XXY), confirming the diagnosis of Klinefelter syndrome.

Klinefelter syndrome: a speech-language and neuropsychological assessment / Síndrome de Klinefelter: avaliação fonoaudiológica e neuropsicológica

ABSTRACT The Klinefelter syndrome is a chromosomal aneuploidy caused by additional X chromosomes in men. The diagnosis is made by clinical observation and karyotype examination. Besides other characteristics, the phenotype involves infertility, hypogonadism, gynecomastia, and cognitive alterations, mainly in the language domain. This paper describes the case of a teenager with Klinefelter syndrome and history of difficulties in the learning process, behavioral and communication problems. The ethical guidelines were followed in the present report. The cognitive-communicative, pragmatic and syntactic profile was drawn from the speech and neuropsychological evaluations. The speech-language assessment showed deficits in expression and comprehension. Difficulties were also found in phonological awareness, mathematical operations, reading and writing, access to the lexicon, alterations in pragmatics and occasionally, in syntactics. The neuropsychological evaluation indicated impairments in tasks that require the identification of similarities, establishment of cause-effect relationships and analogies, demonstrating a compromised reasoning for logical operations, with intellectual level incompatible with the chronological age. This interdisciplinary clinical study favors intervention approaches in rehabilitation, to maximize the potential of the individuals affected, contributing to improve their quality of life.

RESUMO A Síndrome de Klinefelter é uma aneuploidia cromossômica causada por cromossomos X adicionais em homens. O diagnóstico é realizado por meio de observação clínica e exame de cariótipo. O fenótipo envolve, entre outras características, a infertilidade, hipogonadismo, ginecomastia, alterações cognitivas, principalmente no domínio da linguagem. Este trabalho descreve o caso de um adolescente com Síndrome de Klinefelter e histórico de dificuldades no processo de aprendizagem, problemas de comportamento e de comunicação. Cumpriram-se os princípios éticos. Seu perfil cognitivo-comunicativo, pragmático e sintático foi traçado a partir das avaliações fonoaudiológica e neuropsicológica. Os resultados encontrados na avaliação fonoaudiológica foram indicativos de déficits de expressão e compreensão. Além de alterações de consciência fonológica, dificuldades em operações matemática, leitura e escrita, dificuldade de acessar o léxico, alteração de pragmática e, algumas vezes, com alteração na sintática. Os resultados da avaliação neuropsicológica indicaram prejuízos em tarefas que exigiram a identificação de similaridades, estabelecimento de relações de causa-efeito e analogias, demonstrando raciocínio comprometido para operações lógicas, com nível intelectual incompatível à idade cronológica. Este estudo clínico interdisciplinar favorece condutas interventivas nos processos de reabilitação com o intuito de maximizar o potencial do indivíduo afetado, contribuindo para melhoria da qualidade de vida.

Doble aneuploidía: síndromes de Klinefelter y Edwards (48, XXY, +18). Reporte de caso / Double aneuploidy: Klinefelter and Edwards syndromes (48, XXY, +18). Case report

La existencia de una doble aneuploidía en un mismo individuo es una anomalía cromosómica poco frecuente que involucra, mayoritariamente, al par sexual y al cromosoma 21. En el presente artículo, se expone el caso clínico de un niño con la doble aneuploidía 48,XXY,+18. El fenotipo del paciente era coincidente con el síndrome de Edwards. El diagnóstico se efectuó mediante la realización del estudio citogenético de linfocitos de sangre periférica. En la bibliografía revisada, solo se han encontrado 15 casos reportados de pacientes con síndromes de Klinefelter y Edwards.

The co-existence of a double chromosomal abnormality in one individual is a rare event, even more the simultaneous presence of Klinefelter (XXY) and Edwards (trisomy 18) syndrome. The aim of this article is to report the case of a newborn with a double aneuploidy, which consists in the coexistence of Edwards and Klinefelter syndrome. The patient's phenotype correlates mainly with Edwards syndrome. The diagnosis is made by performing the cytogenetics (karyotype) of peripheral blood lymphocytes. Only 15 cases of patients with Klinefelter and Edwards syndromes had been reported in literature so far.

[Double aneuploidy: Klinefelter and Edwards syndromes (48,XXY,+18). Case report]. / Doble aneuploidía: síndromes de Klinefelter y Edwards (48,XXY,+18). Reporte de caso.

The co-existence of a double chromosomal abnormality in one individual is a rare event, even more the simultaneous presence of Klinefelter (XXY) and Edwards (trisomy 18) syndrome. The aim of this article is to report the case of a newborn with a double aneuploidy, which consists in the coexistence of Edwards and Klinefelter syndrome. The patient's phenotype correlates mainly with Edwards syndrome. The diagnosis is made by performing the cytogenetics (karyotype) of peripheral blood lymphocytes. Only 15 cases of patients with Klinefelter and Edwards syndromes had been reported in literature so far.

La existencia de una doble aneuploidía en un mismo individuo es una anomalía cromosómica poco frecuente que involucra, mayoritariamente, al par sexual y al cromosoma 21. En el presente artículo, se expone el caso clínico de un niño con la doble aneuploidía 48,XXY,+18. El fenotipo del paciente era coincidente con el síndrome de Edwards. El diagnóstico se efectuó mediante la realización del estudio citogenético de linfocitos de sangre periférica. En la bibliografía revisada, solo se han encontrado 15 casos reportados de pacientes con síndromes de Klinefelter y Edwards.

Heterozygous Nonsense Mutation in the Androgen Receptor Gene Associated with Partial Androgen Insensitivity Syndrome in an Individual with 47,XXY Karyotype.

There are only 2 patients with 47,XXY karyotype and androgen receptor (AR) gene mutation reported in the literature, and both are diagnosed as complete androgen insensitivity syndrome (CAIS). We report a 22-year-old female with 47,XXY karyotype and atypical external genitalia. Sequencing of AR revealed the heterozygous p.Asn849Lys*32 mutation, and extensive X chromosome microsatellite analysis showed homozygosity for Xp and heterozygosity for Xq, suggesting partial X maternal isodisomy. Partial androgen insensitivity syndrome (PAIS) developed in this case, probably because of the presence of the heterozygous AR mutation and random X- inactivation of the healthy allele. This is the first report of a female patient with 47,XXY karyotype and PAIS phenotype.

Asociación de craneofaringioma y síndrome de Klinefelter en la transición puberal: un desafío diagnóstico / Craniopharyngioma and Klinefelter syndrome during the pubertal transition: A diagnostic challenge

Los craneofaringiomas son de los tumores hipofisarios más frecuentes en la niñez y, sea por su evolución o por el tratamiento que requieren, pueden comprometer el desarrollo puberal. El síndrome de Klinefelter es la causa más frecuente de hipogonadismo hipergonadotrópico en el varón. La presentación concomitante de ambas entidades es extremadamente baja (1/10(9)) y plantea un interrogante acerca de una probable asociación fisiopatológica. Se presenta el caso de un paciente belga de 18 años, con diagnóstico de craneofaringioma en la niñez y panhipopituitarismo luego del tratamiento quirúrgico y radioterápico. Al llegar a los 14 años, se inició la inducción puberal con gonadotropinas. Ante la falta de respuesta clínica, se completó una evaluación genética, que evidenció, de manera homogénea, una trisomía XXY. La falta de respuesta al tratamiento de inducción con gonadotropina exógena reveló la asociación de hipogonadismo primario y secundario, que demostró la importancia del seguimiento multidisciplinario que estos pacientes requieren.

Craniopharyngioma is the most common pituitary tumor in childhood. It can compromise the pubertal development because of its evolution or treatment. Syndrome of Klinefelter is the most common cause of hipergonadotrophic hypogonadism in males. The concomitant presentation of both entities is extremely low (1/10(9)) and the pathophysiological association is questionned. We present the case of a 18-year-old Belgian patient. He had a diagnosis of craniopharyngioma in childhood and he presented with panhypopituitarism after radiotherapy and surgical treatment. At the age of 14, he started pubertal induction with gonadotropin therapy without clinical response. A genetic evaluation confirmed a homogeneous 47, XXY karyotype. Failure of exogenous gonadotropin therapy revealed the hidden association of primary and secondary hypogonadism, demonstrating the importance of the followup and a multidisciplinary approach in these patients.

Androgen Treatment Effects on Motor Function, Cognition, and Behavior in Boys with Klinefelter Syndrome.

OBJECTIVES: To examine the effects of early low-dose androgen on motor, cognitive, and behavioral function in prepubertal boys with Klinefelter syndrome (47,XXY). STUDY DESIGN: Double-blind trial of 84 boys, ages 4-12 years, randomized to oxandrolone (Ox; 0.06?mg/kg daily; n?=?43) or placebo (Pl; n?=?41) for 24 months. Standardized assessments were performed at baseline and every 12 months for 24 months evaluating motor, cognitive, and behavioral function. RESULTS: The 24-month outcomes were better in the Ox vs. Pl group on 1 of 5 primary endpoints (motor function/strength): Bruininks Visual-Motor scale (P?=?.005), without significant differences between the 2 groups for the other 4 components. Secondary analyses suggested improvement in the Ox vs. Pl group in the anxiety/depression (P?=?.03) and social problems (P?=?.01) scales on the Child Behavior Checklist, anxiety (P?=?.04) on the Piers Harris Self Concept Scale, and interpersonal problems (P?=?.02) on the Children's Depression Inventory, without significant differences in hyperactive or aggressive behaviors. CONCLUSIONS: This double-blind, randomized trial demonstrates that 24 months of childhood low-dose androgen treatment in boys with Klinefelter syndrome benefited 1 of 5 primary endpoints (visual-motor function). Secondary analyses demonstrated positive effects of androgen on aspects of psychosocial function (anxiety, depression, social problems), without significant effects on cognitive function, or hyperactive or aggressive behaviors. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00348946.

[Craniopharyngioma and Klinefelter syndrome during the pubertal transition: A diagnostic challenge]. / Asociación de craneofaringioma y síndrome de Klinefelter en la transición puberal: un desafío diagnóstico.

Craniopharyngioma is the most common pituitary tumor in childhood. It can compromise the pubertal development because of its evolution or treatment. Syndrome of Klinefelter is the most common cause of hipergonadotrophic hypogonadism in males. The concomitant presentation of both entities is extremely low (1/109) and the pathophysiological association is questionned. We present the case of a 18-year-old Belgian patient. He had a diagnosis of craniopharyngioma in childhood and he presented with panhypopituitarism after radiotherapy and surgical treatment. At the age of 14, he started pubertal induction with gonadotropin therapy without clinical response. Asociación de craneofaringioma y síndrome de Klinefelter en la transición puberal: un desafío diagnóstico Craniopharyngioma and Klinefelter syndrome during the pubertal transition: A diagnostic challenge A genetic evaluation confirmed a homogeneous 47, XXY karyotype. Failure of exogenous gonadotropin therapy revealed the hidden association of primary and secondary hypogonadism, demonstrating the importance of the followup and a multidisciplinary approach in these patients.

Los craneofaringiomas son de los tumores hipofisarios más frecuentes en la niñez y, sea por su evolución o por el tratamiento que requieren, pueden comprometer el desarrollo puberal. El síndrome de Klinefelter es la causa más frecuente de hipogonadismo hipergonadotrópico en el varón. La presentación concomitante de ambas entidades es extremadamente baja (1/109) y plantea un interrogante acerca de una probable asociación fisiopatológica. Se presenta el caso de un paciente belga de 18 años, con diagnóstico de craneofaringioma en la niñez y panhipopituitarismo luego del tratamiento quirúrgico y radioterápico. Al llegar a los 14 años, se inició la inducción puberal con gonadotropinas. Ante la falta de respuesta clínica, se completó una evaluación genética, que evidenció, de manera homogénea, una trisomía XXY. La falta de respuesta al tratamiento de inducción con gonadotropina exógena reveló la asociación de hipogonadismo primario y secundario, que demostró la importancia del seguimiento multidisciplinario que estos pacientes requieren.