Turner syndrome associated with Down syndrome: about a case / Síndrome Turner asociado a síndrome Down: a propósito de un caso

The coexistence of double aneuploidy of Down and Turner syndromes is rare; most cases have been due to double mitotic errors. The objective of the study was to report a case with monosomy of the X chromosome and trisomy of chromosome 21, in mosaic variety, highlighting the phenotypic effect that the presence of different chromosomal abnormalities can produce and compare with those reported in the literature. A 10-year-old Ecuadorian female, born to a multipregnant mother with 46 years at conception, is seen in consultation with a predominant clinical phenotype of Down syndrome, associated with menarche, presence of pubic and axillary villu, where a karyotype is verified 45 X[7]/47XX+ 21 [3]/46, X, der (X)(: p11.1-> q11.1)[1]/46,XX [1]. The present case is a double Turner-Down aneuploidy, with predominantly X monosomy cell line, who shows important mental retardation and some signs of puberal development not usually in Turner syndrome. These features highlight the clinical importance of doing a karyotype in mental retardation cases and searching low mosaics of another aneuploidies in atypical cases. Its complex chromosomal formula and support with molecular cytogenetics allowed diagnostic confirmation and genetic counseling.

La coexistencia de doble aneuploidía de los síndromes de Down y Turner es rara; la mayoría de los casos se han debido a dobles errores mitóticos. Reportar un caso con trisomía del cromosoma 21 y monosomía del cromosoma en X, en variedad mosaico, que curiosamente presenta un despertar puberal precoz y comparar con los reportados en la literatura. Paciente ecuatoriana de sexo femenino, de 10 años de edad, nacida de madre multigesta con 46 años a la concepción, que es vista en consulta con fenotipo clínico predominante de Síndrome Down, asociado a menarquia y telarquia, donde se constata un cariotipo. El presente caso es el primero informado de mosaicismo de doble aneuploidía de Turner-Down asociado con un despertar puberal precoz. Su fórmula cromosómica compleja y el apoyo con la citogenética molecular permitió la confirmación diagnostica y la asesoría genética.

Síndrome de Turner / Turner's Syndrome / Sindrome de Turner

Introducción: el síndrome de Turner es una enfermedad genética caracterizada por la pérdida total o parcial de un cromosoma X, siendo sus características fundamentales la talla baja, la disgenesia gonadal y hallazgos fenotípicos característicos. Tiene una amplia variabilidad en su forma de presentación. Grandes estudios epidemiológicos muestran que la morbilidad aumenta en mujeres con este síndrome, debido a una amplia gama de enfermedades asociadas, sobre todo cardiovasculares, que eleva la mortalidad de manera significativa. Objetivo: realizar una revisión de la literatura, en base a la presentación de un caso clínico, para recabar información sobre las ultimas pautas de manejo y presentar los nuevos objetivos de tratamiento. Conclusiones: el diagnóstico temprano es fundamental, y tiene características propias y criterios de sospecha según la etapa en la que se efectúa, el reto actual en el manejo de estas pacientes consiste en la formación de un equipo médico multidisciplinario, conformado por una amplia gama de especialistas para el adecuado seguimiento, con el fin de disminuir las complicaciones y ayudar a que la paciente alcance sus objetivos para una vida plena. Se presenta el caso de una paciente con síndrome de Turner vista por el equipo médico en el Hospital Pediátrico del Centro Hospitalario Pereira Rossell, Montevideo-Uruguay.

Introduction: Turner's syndrome is a genetic disease characterized by total or partial loss of an X chromosome, its main features being low height, gonadal dysgenesis and characteristic phenotypic findings. It has a wide variability in its form of presentation. Large epidemiological studies show that morbidity increases in women with this syndrome, due to a wide range of associated diseases, especially cardiovascular disease, which significantly raises mortality. Objectives: to carry out a review of the literature, based on a clinical case in order to gather information regarding the latest treatment guidelines and present the new treatment goals. Conclusions: early diagnosis is essential, and has its own characteristics and suspicion criteria according to the stage in which it is carried out. The present challenge regarding the management of these patients consists of the training of a multidisciplinary medical team made up of a wide range of specialists able to carry out proper follow-up, in order to reduce complications and help the patient live a full life. We present a case of a patient with Turner's syndrome assisted at the Pereira Rossell Hospital Center in Montevideo-Uruguay.

Introdução: a síndrome de Turner é uma doença genética caracterizada pela perda total ou parcial de um cromossomo X, sendo suas características fundamentais de baixa estatura, disgenesia gonadal e achados fenotípicos característicos. Tem uma ampla variabilidade em sua forma de apresentação. Consideráveis (grandes, amplos, extensos) estudos epidemiológicos mostram que a morbidade aumenta em mulheres com essa síndrome, devido a uma ampla gama de doenças associadas, especialmente cardiovasculares, o que aumenta significativamente a mortalidade. Objetivos: realizar uma revisão da literatura, a partir da apresentação de um caso clínico, reunir informações sobre as últimas diretrizes de tratamento e apresentar os novos objetivos do tratamento. Conclusões: o diagnóstico precoce é fundamental, e possui características próprias e critérios de suspeita de acordo com a etapa em que é realizado, o desafio atual na gestão desses pacientes consiste na formação de uma equipe médica multidisciplinar, formada por uma ampla gama de especialistas para o acompanhamento adequado, a fim de reduzir complicações e ajudar a paciente a alcançar uma vida plena. Apresentamos o caso de uma paciente com síndrome de Turner atendido pela equipe médica do Hospital Pediátrico do Centro Hospitalar Pereira Rossell, Montevidéu-Uruguai.

The bone densitometry is normal in Turner syndrome prepubertal patients after height age correction / A densitometria óssea é normal em pacientes pré-púberes com síndrome de turner quando corrigida pela idade estatura

Abstract Objectives: to evaluate the bone mass in prepubertal patients with Turner Syndrome (TS) according to height age (HA) and verify the influence of karyotype and adiposity. Methods: retrospective and analytical study of prepubertal TS patients. The variables analyzed were: karyotype, age at bone densitometry (BD), height, body mass index (BMI) and BD result. The result of the BD was corrected using HA. BMI and BD were calculated on Z score for chronological age (CA) and for HA. Results: thirty-seven prepubertal patients were selected and after exclusion criteria, 13 cases between 10 and 13 years old were included in the study. The BD for HA was significantly higher than for CA (0.39 ± 1.18 x −1.62 ± 1.32), without karyotype (p=0.369) and BMI (p=0.697) influence. Conclusion: prepubertal TS patients present normal BD when corrected for HA, without influence of karyotype and BMI.

Resumo Objetivos: avaliar a massa óssea de pacientes pré-púberes com Síndrome de Turner (ST) de acordo com a idade estatura (IE) e verificar a influência do cariótipo e da adiposidade. Métodos: estudo retrospectivo e analítico de pacientes pré-púberes com ST. As variáveis analisadas foram: cariótipo, idade na realização da densitometria óssea (DO); estatura, índice de massa corporal (IMC) e resultado da DO. Realizou-se a correção do resultado da DO utilizando a IE. O IMC e a DO foram calculados em Z score para idade cronológica (IC) e para IE. Resultados: foram selecionadas 37 pacientes pré-púberes e após critério de exclusão foram incluídas no estudo 13 casos entre 10 e 13 anos de idade. A DO para IE foi significativamente maior que para IC (0,39 ± 1,18 × −1,62 ± 1,32), sem influência do cariótipo (p=0,369) e do IMC (p=0,697). Conclusão: pacientes pré-púberes com ST apresentam DO normal quando corrigida para IE, sem influência do cariótipo e do IMC.

Clinical and cytogenetic characteristics of patients diagnosed with Turner syndrome in a clinical genetics service: cross-sectional retrospective study

ABSTRACT BACKGROUND: Turner syndrome (TS) is a rare genetic disease. Understanding its clinical findings contributes to better management of clinical conditions. OBJECTIVE: To investigate the clinical and karyotypic characteristics of patients diagnosed with TS at two reference services for clinical genetics in southern Brazil. DESIGN AND SETTING: Retrospective cross-sectional study conducted in two clinical genetics services in Porto Alegre (RS), Brazil. METHODS: The sample consisted of 59 patients with TS diagnosed from 1993 to 2019. A review of their medical records was performed and a standard protocol was filled out. RESULTS: The average age of the patients at diagnosis was 15.9 years, and 40.7% were over 13 years old. The largest proportion of them (42.4%) had been referred from an endocrinology department and their constitution was 45,X (40.7%). The most common clinical findings were short stature (85.7%), hypoplastic/ hyperconvex nails (61.2%), low posterior hairline (52.1%) and cubitus valgus (45.8%). There was no difference regarding the presence of short stature (P = 0.5943), number of dysmorphia (P = 0.143), anatomical regions affected and malformations identified through imaging examinations (P = 1.0000), regarding the presence or absence of 45,X constitution. Only 6% of the patients had used growth hormone and 43%, estrogen. CONCLUSION: We found that, in general, patients with TS were being diagnosed late. This has important implications for their treatment. In addition, only a small proportion of the patients were undergoing further examination or evaluation, which appeared to be leading to underdiagnosis of many abnormalities.

Gestación en paciente con insuficiencia ovárica primaria secundaria a mosaicismo de Síndrome de Turner / Pregnancy in a patient with primary ovarian insufficiency owing to a mosaicism of Turner Syndrome

RESUMEN La Insuficiencia Ovárica Primaria se define por una amenorrea secundaria de al menos cuatro meses de duración, deficiencia de esteroides sexuales (estradiol) y altas concentraciones séricas de hormona folículoestimulante (FSH) con al menos un mes de diferencia entre estas determinaciones, en mujeres menores de 40 años. Es una causa insidiosa de infertilidad pero en algunas ocasiones es transitoria y permite una gestación espontánea. El Síndrome de Turner es un trastorno genético caracterizado por la pérdida o anomalías estructurales de un cromosoma X y que afecta a 1 de cada 2.500 mujeres nacidas vivas. Las manifestaciones clínicas varían entre pacientes, pero generalmente se relaciona con talla baja, coartación aórtica, disgenesia gonadal e insuficiencia ovárica primaria. Las técnicas de reproducción asistida como la criopreservación de ovocitos y de tejido ovárico, la maduración in vitro o la donación de ovocitos ofrecen opciones reproductivas en aquellos casos en los que no se produzca un embarazo espontáneo.

ABSTRACT Primary Ovarian Insufficiency is considered a secondary amenorrhea of at least four months duration, sex steroid deficiency (estradiol) and high serum concentrations of follicle stimulating hormone (FSH) with at least one month difference between these determinations, in women under 40 years. It is an insidious cause of infertility but sometimes it is transient and allows a spontaneous pregnancy. Turner syndrome is a genetic disorder characterized by the loss or structural abnormalities of an X chromosome that affects 1 in 2,500 women born alive. Clinical manifestations vary among patients, but it is usually associated with short stature, aortic coarctation, gonadal dysgenesis, and primary ovarian failure. Assisted reproduction techniques such as cryopreservation of oocytes and ovarian tissue, in vitro maturation or oocyte donation offer reproductive options in those cases in which there is no spontaneous pregnancy.

Actualización en el manejo del síndrome de Turner en niñas y adolescentes: revisión de la literatura e Incorporación de recomendaciones de las nuevas guías clínicas / Update on the management of Turner syndrome in girls and adolescents: review of the literature and incorporation of recommendations of the new clinical guidelines

Turner syndrome (TS) is a common disorder (1/2.000 women) that affects multiple organs at different stages of life and needs a multidisciplinary approach. It can be present in women of all ethnicities and is caused by a monosomy of the X chromosome that causes a haploinsufficiency of certain genes. Its main features consist of specific but variables physical characteristics, congenital heart defects, renal anomalies, middle and inner ear diseases, skeletal alterations, and from the endocrinological point of view, short stature and ovarian insufficiency. Given the comorbidities associated with TS, it has been estimated that they have an increased risk of mortality (up to 3 times more) and a reduction in life expectancy of approximately 13 years. Depending on the genotype, the abnormalities can become very subtle, in these cases the diagnosis is late, when the adolescent consults, for example, for primary amenorrhea or an adult woman for infertility. Once the diagnosis is confirmed by a karyotype, these patients must remain in pediatric control in a continuous way to investigate associated pathologies in a timely manner, with periodic evaluations by specialists, such as otolaryngologists, cardiologists, neurologists and endocrinologists, among others. Numerous advances in the care of these patients gave rise to new guidelines published in 2017. In this article we will comment on the main conditions associated with TS and its specific etiology, we will mention what is relevant regarding the genotype-phenotype relationship in this syndrome and we will discuss the fundamental aspects of the control of the TS patient, with emphasis on the treatment of short stature and ovarian insufficiency, as well as the cardiovascular aspects and those related to fertility.

El Síndrome de Turner (ST) es una patología frecuente (1/2.000 mujeres) que afecta múltiples órganos en distintas etapas de la vida y necesita un enfoque multidisciplinario. Se produce por una monosomía del cromosoma X que provoca una haploinsuficiencia de determinados genes. Sus características principales consisten en un fenotipo característico pero variable, con presencia de cardiopatías congénitas, anomalías renales, enfermedades del oído medio e interno, alteraciones esqueléticas, y del punto de vista endocrinológico, talla baja e insuficiencia ovárica. Dadas las comorbilidades asociadas al ST, principalmente cardiovasculares (CV), presentan mayor mortalidad con respecto a la población general (hasta 3 veces más). Dependiendo del genotipo, las anomalías pueden llegar a ser muy sutiles, realizándose en estos casos el diagnóstico en forma tardía, cuando la adolescente consulte, por ejemplo, por amenorrea primaria o una mujer adulta por infertilidad. Una vez confirmado el diagnóstico mediante un cariotipo, estas pacientes deben permanecer en control endocrinológico pediátrico en forma continua hasta la transición hacia adultos, con el fin de pesquisar patologías asociadas en forma oportuna. Por ello requieren evaluaciones periódicas por especialistas, tales como otorrinolaringólogos, cardiólogos, neuropsiquiatras, entre otros. Numerosos avances en el cuidado de estas pacientes, dieron origen a nuevas guías publicadas el 2017. En este artículo comentaremos sobre las principales condiciones asociadas al ST y su etiología específica, mencionaremos lo relevante respecto a la relación genotipo-fenotipo en este síndrome y discutiremos los aspectos fundamentales del control de la paciente con ST, haciendo énfasis en el tratamiento de la talla baja y la insuficiencia ovárica, así como los aspectos CV y los relacionados a fertilidad.

Habilidades sociales: su importancia en mujeres con diagnóstico de Síndrome de Turner / Social skills: their importance for women diagnosed with Turner Syndrome / Habilidades sociais: sua importância em mulheres com diagnóstico de Síndrome de Turner

La Psicología Positiva postula la importancia de trabajar desde una mirada integradora de cada persona incluyendo sus fortalezas y debilidades. Esta mirada resulta importante al trabajar con poblaciones físicas, psicológicas y socialmente vulnerables. El Síndrome de Turner es un trastorno cromosómico determinado por la deleción del cromosoma X en el sexo femenino, siendo la talla y la disgenesia gonadal sus principales características físicas. Las mismas tienen un gran impacto en el desarrollo psicológico de esta población generando problemas en la capacidad de establecer relaciones sociales óptimas. El objetivo del presente trabajo es referenciar la importancia del desarrollo de habilidades sociales en el Síndrome de Turner, principalmente durante la niñez y la adolescencia, considerando que las mismas operan como un recurso salugénico para evitar trastornos mayores en la vida adulta.

Positive Psychology proposes the importance of working based on an integrated view of each person, including their strengths and weaknesses. This view is important for work with physically, psychologically and socially vulnerable populations. Turner Syndrome is a chromosomal disorder determined by the deletion of the X chromosome in females, with size and gonadal dysgenesis as the main physical characteristics.This syndrome has a strong impact on the psychological development of this population, creating problems among women with Turner Syndrome as it affects their ability to establish optimal relationships. The aim of this study is to highlight the importance of developing social skills for women with Turner Syndrome, particularly during childhood and adolescence, considering that these skills act as a healing method that prevents further disorders during adulthood.

A Psicologia Positiva postula a importância de trabalhar a partir de uma visão integradora de cada pessoa, incluindo suas forças e fraquezas. Esta percepção se resulta importante ao trabalhar com populações físicas, psicológicas e socialmente vulneráveis. A Síndrome de Turner é um transtorno cromossômico determinado pela eliminação do cromossomo X no sexo feminino, sendo a estatura e a gonadal dysgenesis suas principais características físicas. Essas têm um grande impacto no desenvolvimento psicológico desta população gerando problemas na capacidade de estabelecer relações sociais ideais. O objetivo do presente trabalho é mostrar a importância do desenvolvimento de habilidades sociais em relação à Síndrome de Turner, principalmente durante a infância e a adolescência, considerando que estas operam como um recurso salugênico para evitar transtornos maiores na vida adulta

Recién nacida normal con sospecha prenatal de monosomía del cromosoma X debido a mosaicismo confinado a la placenta / Normal newborn with prenatal suspicion of X chromosome monosomy due to confined placental mosaicism

La reciente introducción de las pruebas prenatales no invasivas (NIPT, por sus siglas en inglés) basadas en el ADN libre ofrece un método más preciso que los métodos tradicionales de detección en el suero materno para identificar aneuploidías fetales. La eficacia de las pruebas NIPT para detectar los síndromes de Down, Edwards y Patau se ha demostrado en ensayos clínicos. Sin embargo, los enfoques de las pruebas NIPT que aprovechan la información sobre el polimorfismo de un solo nucleótido (SNP, por sus siglas en inglés) tienen el potencial de identificar triploidías, síndromes de microdeleción cromosómica y otras variantes genéticas no habituales. Para destacar este enfoque de las pruebas NIPT, se presenta un caso poco frecuente de monosomía del cromosoma X debido a mosaicismo confinado a la placenta, del que había una sospecha prenatal por el resultado de una prueba prenatal no invasiva basada en el polimorfismo de un solo nucleótido. Los resultados de las pruebas invasivas (amniocentesis) mostraron una pequeña proporción de mosaicismo del cromosoma X (45, X[5]/46, XX[95]). Después del nacimiento, el cariotipo de la niña no reveló anomalías (46 XX), lo que confirmó que el mosaicismo se limitaba a la placenta. Estos resultados ponen de manifiesto la necesidad del consentimiento informado de la paciente, y del minucioso asesoramiento anterior y posterior a las pruebas, para garantizar que comprenda las limitaciones y las ventajas de dichas pruebas, y las repercusiones de los resultados.

The recent introduction of cell-free DNA (cfDNA)-based noninvasive prenatal testing (NIPT) offers pregnant women a more accurate method than traditional serum screening methods for detecting fetal aneuploidies. Clinical trials have demonstrated the efficacy of NIPT for Down, Edwards and Patau syndromes. However NIPT approaches that take advantage of single-nucelotide polymorphism (SNP) information potentially allow the identification of triploidy, chromosomal microdeletion syndromes and other unusual genetic variants. To highlight this approach of NIPT we present a rare case of confined placental X chromosome monosomy mosaicism that was prenatally suspected with a single-nucleotide polymorphism-based noninvasive prenatal test. The results of invasive tests (amniocentesis) showed small proportion of X chromosome mosaicism (45, X[5]/46, XX[95]). After birth karyotype of the girl revealed no abnormalities (46 XX), confirming that mosaicism was limited to the placenta. These results highlight the need of patient's informed consent and thorough pretest and postest counseling to ensure that they understand the limitations and advantages of the tests and the implications of the resultss.

Síndrome de Turner e polimorfismo genético: uma revisão sistemática / Turner syndrome and genetic polymorphism: a systematic review

Objetivo:Apresentar os principais resultados dos estudos que investigaram polimorfismos genéticos em síndrome de Turner, bem como sua associação com alguns sinais clínicos e etiologia desse distúrbio cromossômico.Fontes de dados:Revisão bibliográfica feita no PubMed, sem limite de período, com os seguintes termos: Turner syndrome and genetic polymorphism. Foram identificados 116 artigos e, de acordo com os critérios de inclusão e exclusão, 17 foram selecionados para leitura.Síntese dos dados:Os polimorfismos investigados em pacientes com síndrome de Turner estavam relacionados com déficit de crescimento, que causou baixa estatura, densidade mineral óssea baixa, autoimunidade e anomalias cardíacas, que podem estar presentes com frequências significativas nas pacientes. Também foi verificado o papel dos polimorfismos de único nucleotídeo (SNPs) na etiologia da síndrome de Turner, ou seja, na não disjunção cromossômica.Conclusões:Os polimorfismos genéticos parecem estar associados à síndrome de Turner. Entretanto, por conta dos poucos estudos publicados e dos achados contraditórios, pesquisas em diferentes populações são necessárias para esclarecer o papel dessas variantes genéticas para os sinais clínicos e a etiologia do distúrbio cromossômico.

Objective:To present the main results of the literature on genetic polymorphisms in Turner syndrome and their association with the clinical signs and the etiology of this chromosomal disorder.Data sources:The review was conducted in the PubMed database without any time limit, using the terms Turner syndrome and genetic polymorphism. A total of 116 articles were found, and based on the established inclusion and exclusion criteria 17 were selected for the review.Data synthesis:The polymorphisms investigated in patients with Turner syndrome were associated with growth deficit, causing short stature, low bone mineral density, autoimmunity and cardiac abnormalities, which are frequently found in patients with Turner syndrome. The role of single nucleotide polymorphisms in the etiology of Turner syndrome, i.e., in chromosomal nondisjunction, was also confirmed.Conclusions:Genetic polymorphisms appear to be associated with Turner syndrome. However, in view of the small number of published studies and their contradictory findings, further studies in different populations are needed in order to clarify the role of genetic variants in the clinical signs and etiology of the Turner syndrome.

Variedad de la presentación citogenética en el síndrome de turner, prenatal y postnatal / Cytogenetics variety of presentation turner syndrome, prenatal and postnatal

Antecedentes: El síndrome de Turner (ST) es causado por la ausencia total o parcial del cromosoma X y posee una gran variedad en su presentación citogenética. Objetivos: Determinar la variedad de presentación citogenética y la existencia de diferencias entre los casos diagnosticados in útero y los de diagnóstico postnatal, en pacientes con ST en dos laboratorios de referencia de Cali, Colombia. Métodos: Se realizó un estudio observacional descriptivo de corte transversal, se incluyeron pacientes con diagnóstico de ST, cuyo cariotipo se realizó entre los años 2000 y 2012, en los laboratorios de citogenética de la Universidad del Valle y un instituto de genética de Cali, Colombia. Se recolectó información del reporte del cariotipo, tipo de muestra y tiempo de realización del diagnóstico y se determinó frecuencias y asociaciones estadísticas entre las variables a estudiar. Resultados: Se incluyeron 181 pacientes con fórmula cromosómica compatible con ST; 69 fueron diagnosticados in útero, los demás, en recién nacidos vivos, infantes o adultos. La fórmula cromosómica 45 X0 se encontró en el 95,6 por ciento de los casos de diagnóstico prenatal y 58 por ciento de los de diagnóstico postnatal. Se aplicó la prueba del test exacto de Fisher, comparando los múltiples subgrupos de la variedad de presentación citogenética de diagnóstico prenatal y postnatal, encontrándose diferencias estadísticamente significativas en la distribución de las dos poblaciones evaluadas (p<0,001). Conclusiones: Existen diferencias significativas en los cariotipos de los pacientes con ST diagnosticados in útero, respecto a los diagnosticados en vida extrauterina. Se postula que esa diferencia tendría una explicación biológica sobre la posibilidad de muerte in útero por la ausencia total del cromosoma X.

Background: Turner syndrome is caused by the complete or partial absence of chromosome X and has a great variety in their cytogenetic presentation. Objectives: To determine the variety of cytogenetic presentation and the presence of differences between cases diagnosed in uterus and postnatally, in patients with Turner syndrome at two reference laboratories of Cali, Colombia. Methods: A descriptive cross-sectional study was performed. We included patients with cytogenetic diagnosis of Turner syndrome performed between 2000 and 2012 at cytogenetic laboratories of Universidad del Valle and a genetic institute in Cali, Colombia. The information of karyotype result, type of sample and the diagnosis moment was collected, determining frequencies and statistical associations. Results: 181 patients with Turner's chromosomic presentation; 69 were diagnosed in uterus, the other as live newborns, infants or adults. Chromosomal formula 45X0 was found in 95.6 percent of cases with prenatal diagnosis and 58 percent of postnatal diagnosis. Fisher's test was applied, comparing the cytogenetic presentations of prenatal and postnatal diagnosis, statistically significant difference in the distribution of the two populations evaluated was found (p<0.001). Conclusions: There are significant differences in the karyotypes of patients with ST diagnosed in utero, compared to those diagnosed in postnatal life. We hypothesize that this difference would have a biological explanation due to a higher probability of death in utero by the complete absence of chromosome X.

Estudio preliminar sobre el tratamiento con hormona de crecimiento humana recombinante en el síndrome de Turner / Preliminary study on the recombinant human growth hormone treatment of Turner's syndrome

Introducción: los pacientes con síndrome de Turner presentan una monosomía parcial o total del gonosoma X, disgenesia gonadal, diversos rasgos físicos típicos, baja talla e infantilismo sexual. Objetivo: evaluar el efecto del tratamiento con hormona de crecimiento recombinante sobre la talla en las pacientes con el diagnóstico clínico y cromosómico de síndrome de Turner. Métodos: se realizó un estudio de tipo descriptivo y retrospectivo a pacientes con síndrome de Turner atendidas en consultas externas en el Departamento de Endocrinología Pediátrica del Instituto Nacional de Endocrinología, desde mayo de 2003 hasta mayo de 2004. La muestra estuvo constituida por 19 niñas. Se confeccionaron dos grupos, uno con aquellas pacientes que recibieron tratamiento con hormona de crecimiento recombinante (n= 9) a una dosis de 0,14 UI/kg/día, administrada vía subcutánea entre las 8:30 y 9:30 pm, que se conoció como grupo A. El segundo quedó conformado con las pacientes que no recibieron dicha hormona (n= 10), denominado grupo B. Los datos necesarios para la investigación fueron obtenidos de la revisión de las historias clínicas. Resultados: un incremento de la talla en el grupo A, que inició el estudio con una talla basal media de 131,7 ± 7,5 cm, para alcanzar una talla media, después de un año de tratamiento, de 137,9 ± 7,1 cm, con una velocidad de crecimiento media en ese año de 6,2 ± 2,3 cm/año. La comparación de ambos grupos después de un año de estudio mostró diferencias significativas en la talla media al año (p= 0,0071) y la velocidad de crecimiento media al año (p= 0,0032). Conclusiones: el tratamiento con hormona de crecimiento recombinante durante el primer año resultó efectivo, al acelerar significativamente la velocidad de crecimiento en las niñas con síndrome de Turner. La ganancia de peso corporal resultó adecuada durante el periodo de estudio, pues se logró mantener una valoración nutricional estable sin modificaciones en el canal percentilar. La inducción de la pubertad no cambió el pronóstico de la talla al final del estudio(AU)

Introduction: Turner's syndrome patients present with total or partial monosomy of X gonosome, general disgenesia, several typical physical traits, short height and sexual infantilism. Objective: to evaluate the effect of recombinant human growth hormone-based treatment on the height of patients clinically and chromosomally diagnosed as Turner's syndrome subjects. Methods: a retrospective and descriptive study was conducted in Turner's syndrome patients, who had been seen from May 2003 to May 2004 at the pediatric endocrinology department of the National Institute of Endocrinology. The sample was made up of 19 girls divided into 2 groups. Group A comprised patients who were treated with recombinant human growth hormone (n= 9) at a dose of 0.14 IU/kg/day subcutaneously administered from 8:30 to 9:30 pm. Group B included the patients who did not receive this treatment (n= 10). The required data for the research stemmed from the medical history check-ups. Results: increase of the Group A patients' height, whose mean basal height at the beginning of the study was just 131.7 ± 7.5 cm and after one year of treatment, they reached 137.9 ± 7.1 cm, at a rate of average growth of 6.2 ± 2.3 cm/year. The comparison of both groups after one year showed significant differences in mean height (p= 0.0071) and mean growth a year (p= 0.0032). Conclusions: the treatment of these patients with the recombinant growth hormone during the first year was effective, since it markedly accelerated the rate of growth in girls with Turner's syndrome. The body weight gain proved to be adequate in the study period, because it managed to keep steady nutritional assessment without changes in the percentile canal. Inducement to puberty did not alter the final height prognosis at the end of the study(AU)

Body composition in Egyptian Turner syndrome girls.

OBJECTIVE: This cross-sectional study was undertaken to construct the new body fat % curve and provide body composition reference data for adolescent girls with Turner syndrome (TS). They diagnosed cytogenetically by blood karyotyping and not treated with growth hormone (GH). MATERIALS AND METHODS: The study included 70 TS girls from age 13 years to age 17 years. Body composition was measured by bioelectrical impedance. Smoothed centile charts were derived by using the least mean square (LMS) method. RESULTS: The new body fat curves reflect the increase of body fat mass (FM) from age 13 years to age 17 years. Body FM % of Egyptian TS girls was lower when compared with age-matched American untreated TS girls. CONCLUSION: This study presents the new body fat curves and reference values of body composition for untreated Egyptian TS adolescent girls. The present charts can be used for direct assessment of body FM % for Egyptian TS girls and evaluation for cases on GH treatment or other growth promoting therapy.

Spontaneous puberty in girls with early diagnosis of Turner syndrome / Puberdade espontânea em meninas com diagnóstico precoce de síndrome de Turner

OBJECTIVE: To verify if the frequency of spontaneous pubertal development among girls with Turner syndrome (TS) diagnosed in infancy and childhood is greater than that of patients diagnosed later. SUBJECTS AND METHODS: Thirty three girls aged < 10 years at the time of diagnosis were evaluated regarding pubertal development. The frequency of spontaneous puberty was compared with that of girls aged > 13 years diagnosed at the same service. RESULTS: Sixteen of 32 informative patients had signs of spontaneous puberty, a frequency greater than that of patients diagnosed later. In six patients, there was no progression of puberty; menarche occurred in six, and one became pregnant, but the fetus was a stillborn. Spontaneous puberty was absent in all cases with 45,X karyotype. CONCLUSIONS: The greater prevalence of spontaneous puberty in girls whose diagnosis was not based on pubertal delay suggests that, among those diagnosed later, there is a bias towards patients with hypogonadism. Arq Bras Endocrinol Metab. 2012;56(9):653-7.

OBJETIVO: Verificar se a frequência de puberdade espontânea em meninas com síndrome de Turner (ST) diagnosticadas na infância é superior a de pacientes diagnosticadas posteriormente. SUJEITOS E MÉTODOS: Foram avaliadas 33 meninas < 10 anos ao diagnóstico quanto ao desenvolvimento puberal. A frequência de puberdade espontânea foi comparada com a de pacientes com mais de 13 anos diagnosticadas no mesmo serviço. RESULTADOS: Dezesseis das 32 pacientes informativas tiveram sinais puberais espontâneos, frequência superior a daquelas diagnosticadas posteriormente. Em seis delas, não houve progressão da puberdade; a menarca ocorreu em seis casos e uma paciente ficou grávida, porém o feto foi natimorto. Em todos os casos com cariótipo 45,X não ocorreu puberdade espontânea. CONCLUSÕES: A maior prevalência de puberdade espontânea em meninas cujo diagnóstico não se baseou em atraso puberal sugere que naquelas detectadas posteriormente haja distorção em favor de pacientes com hipogonadismo. Arq Bras Endocrinol Metab. 2012;56(9):653-7.

The use of fluorescence in situ hybridization in the diagnosis of hidden mosaicism: apropos of three cases of sex chromosome anomalies / O uso da hibridação in situ com fluorescência no diagnóstico de mosaicismo oculto: a propósito de três casos de anomalias de cromossomos sexuais

FISH has been used as a complement to classical cytogenetics in the detection of mosaicism in sex chromosome anomalies. The aim of this study is to describe three cases in which the final diagnosis could only be achieved by FISH. Case 1 was an 8-year-old 46,XY girl with normal female genitalia referred to our service because of short stature. FISH analysis of lymphocytes with probes for the X and Y centromeres identified a 45,X/46,X,idic(Y) constitution, and established the diagnosis of Turner syndrome. Case 2 was a 21-month-old 46,XY boy with genital ambiguity (penile hypospadias, right testis, and left streak gonad). FISH analysis of lymphocytes and buccal smear identified a 45,X/46,XY karyotype, leading to diagnosis of mixed gonadal dysgenesis. Case 3 was a 47,XYY 19-year-old boy with delayed neuromotor development, learning disabilities, psychological problems, tall stature, small testes, elevated gonadotropins, and azoospermia. FISH analysis of lymphocytes and buccal smear identified a 47,XYY/48,XXYY constitution. Cases 1 and 2 illustrate the phenotypic variability of the 45,X/46,XY mosaicism, and the importance of detection of the 45,X cell line for proper management and follow-up. In case 3, abnormal gonadal function could be explained by the 48,XXYY cell line. The use of FISH in clinical practice is particularly relevant when classical cytogenetic analysis yields normal or uncertain results in patients with features of sex chromosome aneuploidy. Arq Bras Endocrinol Metab. 2012;56(8):545-51.

FISH tem sido usado como um complemento para a citogenética clássica na detecção de mosaicismo em anomalias de cromossomos sexuais. O objetivo deste trabalho é descrever três casos nos quais o diagnóstico final só foi obtido por meio de FISH. O caso 1 é uma menina de 8 anos, 46,XY, com genitália feminina normal, encaminhada ao nosso setor devido à baixa estatura. A análise de linfócitos por FISH com sondas centroméricas de X e Y identificou a constituição 45,X/46,X,idic(Y) e estabeleceu o diagnóstico de síndrome de Turner. O caso 2 é um menino de 21 meses, 46,XY, com ambiguidade genital (hipospadia peniana, testículo à direita e gônada disgenética à esquerda). FISH de linfócitos e mucosa oral identificou o cariótipo 45,X/46,XY, levando ao diagnóstico de disgenesia gonadal mista. O caso 3 é um rapaz de 19 anos, 47,XYY, com atraso de desenvolvimento neuromotor, dificuldade de aprendizado, problemas psicológicos, alta estatura, testículos pequenos, gonadotrofinas elevadas e azoospermia. FISH de linfócitos e mucosa oral identificou a constituição 47,XYY/48,XXYY. Os casos 1 e 2 ilustram a variabilidade fenotípica do mosaico 45,X/46,XY e a importância da detecção da linhagem 45,X na avaliação e na condução dos casos. No caso 3, a função gonadal anormal pôde ser explicada pela linhagem 48,XXYY. O uso de FISH na prática clínica é particularmente relevante quando a análise citogenética clássica traz resultados normais ou incertos em pacientes com quadro sugestivo de uma aneuploidia de cromossomos sexuais. Arq Bras Endocrinol Metab. 2012;56(8):545-51.

Endocrine diseases, perspectives and care in Turner syndrome / Doenças endócrinas, perspectivas e cuidados na síndrome de Turner

Turner syndrome is a frequent chromosome disorder in clinical practice. It is characterized by short stature, gonadal dysgenesia and multisystemic involvement, responsible for a high morbidity and reduced life expectancy. The aim of the present paper is to describe the endocrinopathies and major problems at different ages, and to present suggestion for follow-up care in these patients.

A síndrome de Turner é uma doença cromossômica frequente na prática clínica. É caracterizada pela baixa estatura, disgenesia gonadal e alterações em diversos sistemas, o que leva a uma alta morbidade e diminuição da expectativa de vida. O objetivo do presente estudo é descrever as endocrinopatias e outros problemas em cada idade e apresentar uma sugestão de cuidados e segmentos dessas pacientes.

Estatura final (EF) em síndrome de Turner (ST): experiência de 76 casos acompanhados na Unidade de Endocrinologia Pediátrica do Hospital de Clínicas da Universidade Federal do Paraná / Final height (FH) in Turner syndrome (TS): experience of 76 cases followed at the Pediatric Endocrinology Unit, Hospital de Clinicas, Federal University of Paraná

Objetivo: Relatar estatura final (EF) em 76 pacientes com síndrome de Turner (ST). Materiais e métodos: Revisão de prontuários e avaliação dos escores z: da estatura alvo (EA) e EF segundo o NCHS/CDC/2000 e da EF segundo Lyon e cols. Resultados: Pacientes foram classificados em três grupos: A (n = 16), tratamento com estrogênios e progestágenos; B (n = 21), tratamento com oxandrolona; C (n = 39), tratamento com hormônio de crescimento (GH) e oxandrolona. Não houve diferença no escore z da EA entre os grupos e no escore z da EF entre A e B. O escore z da EF do grupo C foi maior que o dos outros grupos, maior que 2 DP segundo Lyon e no percentil 3 da curva NCHS/CDC. Análise de regressão múltipla mostrou tipo de tratamento (p < 0,001) e estatura materna (p = 0,02) como fatores que mais influenciaram a EF. Conclusão: GH mais OX e estatura materna contribuíram significativamente para aumento da EF na ST.

Objective: To report the final height (FH) of 76 patients with Turner syndrome (TS). Materials and methods: Review of the files and calculation of z scores: of target height (TH), and FH according to NCHS/CDC/2000 and FH according to Lyon and cols. Results: Patients were classified in three groups: A (n = 16), treatment with estrogens and progestogens; B (n = 21), treatment with oxandrolone (OX); C (n = 39), growth hormone (GH) plus OX. The z score of TH was not different among the groups and z score of FH was not different between A e B. Z score of FH of group C was greater than the other groups, > 2SDS of Lyon's curve and fitted on the 3rd percentile of NCHS/CDC. Multiple regression analysis showed type of treatment (p < 0.001) and maternal height (p = 0.02) as most influencing factors on FH. Conclusion: GH plus OX and maternal height contributed significantly to enhance FH of TS patients.

Endotelium in Turner syndrome with capillaroscopy / Endotélio na síndrome de Turner com capilaroscopia

OBJECTIVE: The aim of this study was to assess the endothelium function in patients with Turner syndrome using videocapillaroscopy and to compare the results with healthy control. METHODS: Subjects and controls were studied in a temperature-controlled room, 20 days after no nailfold manipulations. The capillaries were visualized by a microscope connected to a television and a computer. The test of post-occlusive reactive hyperemia was performed using a sphygmomanometer attached to the fourth left finger, 20mmHg above maximum arterial pressure during 1 minute, and the following patterns were studied: area of transverse segment, maximal post-ischemia area and time to reach maximal post-ischemia area. RESULTS: The value of measure of transverse segment projected area , the maximal postischemia area of hand nailfold capillary loops using computerized videophotometry and the time to reach maximal post ischemia area were studied in 40 patients with Turner syndrome and 26 healthy women controls of comparable age (20±7.5 versus 18±8.1 years old; p=0.57). There were differences between transverse segment area (706.8±139.1 versus 548.8±117.2; p=0.001). Maximal post-ischemia area (891.3±226.1 versus 643.5±134.3; p=0.001) and the time to reach it (10.8±4.3 versus 5.5±2.5; p=0.001) were different between patients and controls. CONCLUSIONS: Changes of capillary response to ischemia could be observed in patients with Turner syndrome using videocapillaroscopy when they were compared to a healthy control group.

OBJETIVOS: O objetivo deste estudo foi avaliar a função endotelial de pacientes com síndrome de Turner, utilizando a videocapilaroscopia e comparar os resultados com grupo controle saudável. MÉTODOS: Pacientes e controles foram estudados em sala com temperatura controlada, após 20 dias, sem a manipulação das cutículas. Os capilares foram visualizados por microscópio conectado a televisão e computador. O teste de hiperemia reativa pós-oclusiva foi realizado utilizando-se esfigmomanômetro fixado no quarto quirodáctilo da mão esquerda, 20mmHg acima da pressão arterial máxima durante 1 minuto, e os seguintes parâmetros foram estudados: área do segmento transverso, área máxima pós-hiperemia e tempo para alcançar a área máxima pós-hiperemia. RESULTADOS: O valor da área do segmento transverso, área máxima pós-hiperemia dos capilares da região da mão usando-se a videocapilaroscopia computadorizada e o tempo para alcançar a área pós-hiperemia foram estudadas em 40 pacientes com síndrome de Turner e 26 controles do sexo feminino pareados para idade (20±7,5 versus 18±8,1 anos; p=0,57). Houve diferenças nos grupos quanto à área do segmento transverso (706,8±139,1 versus 548,8±117,2; p=0,001). A área máxima pós-hiperemia (891,3±226,1 versus 643,5±134,3; p=0,001) e o tempo para alcançá-la (10,8±4,3 versus 5,5±2,5; p=0,001) foram significativamente diferentes entre pacientes e controles. CONCLUSÃO: Houve alterações na resposta do capilar à isquemia em pacientes com síndrome de Turner utilizando-se videocapilaroscopia quando comparados ao grupo controle saudável.

The cytogenetic examination as a tool for the diagnosis of chromosomal disorders / Examinación citogenética como herramienta para el diagnóstico de los desórdenes cromosómicos

Clinically significant chromosomal abnormalities occur in about 1 percent of children born alive. The objective of this work was to offer the patients and the families in the community for the service of the Integrated Clinic of Uniara Health (Araraquara and region), the examination of cariotype (cytogenetic study) for confirmation or exclusion of the diagnostic suspicion of chromosomal abnormalities as well as information (genetic counseling) for the prevention of occurrence and/or recurrence of these anomalies. In the period of one year and four months these were carried out in the Integrated Clinic of Uniara Health and directed for the Laboratory of Cytogenetic Human of the same institution in 66 cytogenetic studies. In 44 patients (66.6 percent) the results were normal. In 22 (33.3 percent) examinations, alterations were found, meaning that the respective clinical pictures are decurrent of chromosomic alterations. The first cause within alterations noted was Down syndrome with a total of 15 examinations or 68.1 percent, the second cause of chromosomal anomaly was the Turner syndrome where the most important factor is 45, X, where 2 karyotypes of this type or 9.1 percent were found, syndromes as (Eduards syndrome, Patau syndrome, 3p- syndrome, 4p- syndrome and 6p-syndrome) diagnosed in our laboratory appeared less frequently corresponding to 22.7 percent of the studied anomalies. The work carried out constitutes a necessary diagnosis of the main chromosomal abnormalities through a low cost technique; it can be carried out easily and is reliable, making the cytogenetic examination available to the community and contributing significantly to the quality of life of patients.

Las anormalidades cromosómicas, clínicamente significativas, se presentan en aproximadamente 1 por ciento de los niños nacidos vivos. Este trabajo tiene el objetivo de ofrecer a los pacientes y /o a sus familiares el servicio de la Clínica Integrada de la Salud de Uniara (Araraquara y Región), el examen de cariotipo (estudio citogenético) para la confirmación o la exclusión de sospecha de anomalías cromosomales diagnosticadas, así como otorgar información (consejo genético) para la prevención de las posibles anomalías y /o la repetición de éstas. En un año y cuatro meses fueron realizados 66 estudios de citogenética en la Clínica Integrada de Uniara, dirigida por el Laboratorio de Citogenética Humana de la misma institución. En 44 pacientes (66,6 por ciento) los resultados fueron normales. En 22 (33,3 por ciento) de los exámenes, se encontraron alteraciones, compatibles con alteraciones cromosómicas. La primera causa de anomalías cromosómica fue el síndrome de Down, totalizando 15 exámenes (68,1 por ciento), la segunda causa fue el síndrome de Turner, con dos cariotipos (9,1 por ciento) en la forma más importante 45, X. Por otra parte, se encontró que los síndromes de Eduards, de Patau, 3p-síndrome de Down, síndrome 4p-6p, diagnosticados en nuestro laboratorio, presentaban baja frecuencia de aparición, representando el 22,7 por ciento de las anomalías estudiadas. Este trabajo permitió realizar un diagnóstico preciso de las anomalías cromosomales, principalmente a través de una técnica de bajo costo, fácil ejecución y buena confiabilidad, técnicas que están disponibles para el examen citogenético para la comunidad y así contribuir de manera significativa en la calidad de vida de los pacientes.

Fatores associados a atraso no diagnóstico da síndrome de turner / Variables associated with diagnostic delay in turner syndrome / Investigación de factores asociados a retraso en el diagnóstico del síndrome de turner

OBJETIVO: Investigar as possíveis razões do atraso no diagnóstico da síndrome de Turner (ST), ou seja, aquele realizado após a idade em que se pode estabelecer o atraso puberal. MÉTODOS: Estudo transversal com obtenção de dados dos prontuários de 29 pacientes com ST diagnosticadas com mais de dois anos, entre 2004 e 2007. Foram comparados antecedentes pessoais e familiares e dados de exame físico das pacientes diagnosticadas com menos de 13 anos (limite a partir do qual se pode caracterizar atraso puberal em meninas) com os daquelas diagnosticadas após os 13 anos por meio dos testes t de Student e exato de Fisher. RESULTADOS: Não houve diferenças significativas quanto à estatura materna e da própria paciente, história de afecções associadas (consideradas individualmente), escolaridade dos pais, recorrência familiar de baixa estatura, presença de cada sinal dismórfico isoladamente e total de sinais observados. Os dois grupos diferiram quanto à presença de ao menos uma afecção sugestiva dessa síndrome (associada ao diagnóstico mais precoce) e ao número de irmãos (maior no diagnóstico tardio e associado à menor escolaridade materna). CONCLUSÕES: O diagnóstico precoce relacionou-se mais à presença de alguma das afecções associadas à ST (possivelmente determinando-se encaminhamento a serviços de maior complexidade) do que a sinais dismórficos. Há indicações de que déficit de crescimento menos evidente, dificuldade dos médicos em reconhecer anomalias sugestivas dessa síndrome e determinantes socioeconômicos contribuam para o atraso no diagnóstico. É necessário enfatizar na formação pediátrica o reconhecimento do espectro clínico dessa síndrome e ampliar os serviços públicos de genética.

OBJECTIVE: To investigate the possible reasons for diagnostic delay in Turner syndrome (TS), i.e., a diagnosis made after the age when pubertal delay may be established. METHODS: Cross-sectional study with data obtained from the records of 29 TS patients aged more than two years who were diagnosed between 2004 and 2007. Data on personal and family history and physical examination from patients diagnosed before 13 years old (age limit from which pubertal delay may be characterized in girls) were compared to those of girls diagnosed after 13 years by Fisher exact test and Student's t-test. RESULTS: No significant differences were noted regarding mothers' and patients' stature, personal history of TS-associated diseases (considered individually), parental schooling, familial recurrence of short stature, presence of each dysmorphic feature considered separately, and total number of dysmorphic features. The two groups differed regarding the presence of at least one TS-associated disease (which was associated to early diagnosis) and number of siblings (which was higher among patients with delayed diagnosis and associated with lower maternal schooling). CONCLUSIONS: Early diagnosis was more associated with the presence of a TS-associated disease (which may have required referral to secondary or tertiary health care services) than with the presence of dysmorphic signs. The results indicate that less evident growth deficit, physicians' inability to recognize abnormalities associated with TS and socioeconomic aspects may contribute to diagnostic delay. Pediatric training should emphasize recognition of the clinical spectrum of TS and public genetic services should be expanded.

OBJETIVO: Investigar las posibles razones del retraso en el diagnóstico del síndrome de Turner (ST), es decir, aquél realizado después de la edad en que se puede establecer retraso puberal. MÉTODOS: Estudio transversal con obtención de datos de los prontuarios de 29 pacientes diagnosticadas con ST mayores de 2 años de edad entre 2004 y 2007. Se compararon antecedentes personales y familiares y datos de examen físico de las pacientes diagnosticadas a una edad menor de 13 años (límite a partir del cual se puede caracterizar retraso puberal en niñas) con los de aquellas diagnosticadas después de los 13 años mediante las pruebas t y chi-cuadrado. RESULTADOS: No hubo diferencias significativas respecto a la estatura materna y de la paciente misma, historial de afecciones asociadas (consideradas individualmente), escolaridad de los padres; recurrencia familiar de baja estatura, presencia de cada señal dismórfica aislada y total de señales observadas. Los dos grupos difirieron respecto a la presencia de al menos una afección sugestiva de ese síndrome (asociada al diagnóstico más temprano) y al número de hermanos (mayor en el diagnóstico tardío y asociado a la menor escolaridad materna). CONCLUSIONES: El diagnóstico temprano se relacionó más a la presencia de alguna de las afecciones asociadas al ST (posiblemente determinando encaminamiento a servicios de mayor complejidad) que a señales dismórficas. Hay indicaciones de que déficit de crecimiento menos evidente, dificultades de los médicos en reconocer anomalías sugestivas de ese síndrome y factores socioeconómicos contribuyan para el retraso en el diagnóstico. Es necesario enfatizar en la formación pediátrica el reconocimiento del espectro clínico de ese síndrome y ampliar los servicios públicos de genética.