49,XXXXY: investigação da idade no diagnóstico, apresentação clínica e tratamento: uma revisão narrativa da literatura / 49,XXXXY: age investigation in diagnosis, clinical and treatment: a narrative review review of the literature

O cariótipo 49,XXXXY, uma variante rara da Síndrome de Klinefelter, acomete 1:85.000­100.000 nascidos vivos do sexo masculino e surge a partir de uma dupla não disjunção durante as duas rodadas da meiose (I e II) materna. No entanto, as pesquisas envolvendo indivíduos com essa constituição cromossômica são limitadas. Deste modo, este estudo tem como objetivo geral caracterizar a idade no diagnóstico, a apresentação clínica e o tratamento de indivíduos 49,XXXXY. Foi realizada uma revisão da literatura na base de dados PubMed utilizando os descritores 49,XXXXY and diagnosis e 49,XXXXY. Os critérios de inclusão foram: artigos originais e relato de caso, idioma inglês, versão completa disponível online gratuitamente e que contenham as informações que respondam integralmente ao objetivo geral. Os resultados dos 20 estudos incluídos nessa revisão mostraram que a identificação de indivíduos com cariótipo 49,XXXXY ocorre geralmente após o nascimento, sendo que o diagnóstico no pré-natal é extremamente raro. A presença de diversas anomalias congênitas pode contribuir significativamente para o diagnóstico precoce, ao contrário de pacientes com cariótipo 47,XXY, que geralmente são assintomáticos até a puberdade. Nossos achados podem contribuir para despertar a atenção dos profissionais de saúde no reconhecimento desse distúrbio genético, visto que o diagnóstico precoce dessa síndrome permite o tratamento adequado mais rapidamente, a fim de se obter menor impacto no desenvolvimento global desse indivíduo, com consequente melhora na sua qualidade de vida.

Sordera neurosensorial congénita con malformación de oído interno ligada al X en una familia mexicana / Congenital sensorineural deafness X-linked, with inner ear malformation in a Mexican family

Introducción. Las sorderas o hipoacusias prelinguales son de etiología genética entre el 60 y el 68% de los casos; de estos, del 20 al 40% son malformaciones del oído interno. De los casos de hipoacusia no sindrómica ligada al X se han descrito siete tipos. De las malformaciones de oído interno, la partición coclear incompleta tipo III es la menos frecuente.Objetivo. Presentar el reporte clínico-genético de una familia mexicana, con indi-viduos varones afectados por sordera neurosensorial congénita con malformación de oído interno. Material y Métodos. Se realizó estudio de una familia en la que nueve miembros presentaban sordera. Se estudiaron cuatro de ellos y una madre sin manifestaciones, a través del estudio clínico general por médico genetista, el estudio audiológico (otos-copía y audiometría) por médico audiólogo y el estudio de tomografía computada (TC) por médico radiólogo.Resultados. Los pacientes estudiados presentaron sordera neurosensorial congéni-ta, de severa a profunda bilateral. A través de la TC, se evidenció malformación de oído interno. Tres pacientes presentaron partición coclear incompleta tipo III y un paciente partición incompleta tipo I. Debido al estudio clínico y al árbol genealógico, se definió diagnóstico de hipoacusia neurosensorial no sindrómica ligada al X. La TC de la madre sin manifestaciones no presentó evidencia de malformaciones en oído interno (MOI).Conclusión. El estudio de imagen es fundamental para definir presencia o no de MOI en todos los pacientes con hipoacusia y así poder guiar la terapéutica y el aseso-ramiento genético, así como realizar los estudios moleculares más adecuados

Introduction. The pre-lingual deafness or hearing loss are of genetic cause in be-tween 60% and 68% of cases, among these, between 20% and 40% are malforma-tion of the inner ear. From the non-syndromic hearing loss cases that are linked to the X chromosome, seven types have been described. Among these inner ear malforma-tions, incomplete cochlear partition type III is the less frequent.Objective. Present the clinical genetical report of a Mexican family, with male in-dividuals affected by congenital neurosensory deafness with inner ear malformation.Materials and methodology. A study on a family in which nine members were affected by deafness was done. Four of them, plus a mother without manifestation, were studied through a general clinical study by a geneticist, an audiological study (otoscopy and audiometry) by an audiologist, and a computed tomography (CT) scan by a radiologist.Results. The studied patients presented congenital neurosensory deafness, from se-vere to deep bilateral. Via the CT, the inner ear malformation was made clear. Three of the patients presented incomplete cochlear partition type III and one patient in-complete cochlear partition type I. Due to the clinical study and the family tree, it was diagnosed non-syndromic neurosensory deafness linked to X. The CT of the mother without manifestation did not show evidence of inner ear malformations.Conclusion. The study by image is fundamental to define whether there is or not a presence of inner ear malformations in any patient with heading loss to be able to guide the therapeutics and the genetic counseling, as well as to make more accurate molecular studies

La desventaja de los hombres frente a la Covid-19: análisis de la influencia del sexo sobre la respuesta inmunitaria ante la infección por SARS-Cov-2 / The disadvantage of men against COVID-19: analysis of the influence of sex on the immune response to SARS-CoV-2 infection

mundo se encuentra en medio de la pandemia de la enfermedad por coronavirus 2019 (COVID-19). En la mayoría de los países, la tasa de mortalidad, así como, la severidad de la enfermedad es más alta en hombres que en mujeres. Este sesgo sexual sugiere que los hombres son más propensos a desarrollar complicaciones graves o a sucumbir a las mismas, lo que conduce a la muerte. Por lo tanto, es importante comprender los elementos biológicos basados en el sexo que inciden en la respuesta inmunitaria. El objetivo de ésta revisión fue hacer un análisis en relación a la evidencia disponible sobre los diferentes factores que permitirían explicar esta disparidad sexual. Abordamos las diferencias en la respuesta inmunitaria en ambos sexos tomando en cuenta el aspecto genético, hormonal y el papel del sistema renina-angiotensina. Para ello, se realizó una búsqueda minuciosa en diferentes bases de datos utilizando las siguientes palabras clave: (Diferencia de sexo, genética, hormonas sexuales, COVID-19, SARS-CoV-2, respuesta inmunitaria, inflamación, hombres, mujeres). Los resultados de nuestro análisis ofrecen una comprensión más clara sobre la influencia de las diferencias sexuales en la capacidad de respuesta a una infección, con especial énfasis en la infección por SARS-CoV-2. Conocer estos factores no solo ayudará a comprender mejor la patogenia de la COVID-19, sino, además, guiará el diseño de terapias efectivas para la medicina personalizada basada en las diferencias sexuales

The world is during the 2019 coronavirus disease pandemic (COVID-19). In most countries, the mortality rate, as well as, the severity of the disease is higher in men than in women. This sex bias suggests that men are more likely to develop severe complications or succumb to severe complications, leading to death. Therefore, it is important to understand the sex-based biological elements that influence the immune response. The aim of this review was to review the available evidence on the different factors that could explain this sex disparity. We addressed the differences in the immune response in both sexes taking into account genetic, hormonal and the role of the renin-angiotensin system. For this purpose, a thorough search was performed in different databases using the following keywords: (Sex difference, genetics, sex hormones, COVID-19, SARS-CoV-2, immune response, inflammation, men, women). The results of our analysis provide a clearer understanding on the influence of sex differences on the ability to respond to an infection, with special emphasis to SARS-CoV-2 infection. Knowing these factors will not only help to better understand the pathogenesis of COVID-19, but will also guide the design of effective therapies for personalized medicine based on sex differences.

Cytogenetic analysis of an amniotic sample with X chromosome abnormality signaled by non-invasive prenatal testing / 中华医学遗传学杂志

OBJECTIVE@#To determine the chromosomal karyotype of a fetus with copy number variation (CNV) of the X chromosome signaled by non-invasive prenatal testing (NIPT).@*METHODS@#NIPT was performed on the peripheral blood sample taken from the pregnant women. Amniotic fluid and cord blood samples were subjected to conventional G banded karyotyping, and were further analyzed by high-throughput sequencing for chromosome microdeletion/microduplication. The results were then verified by fluorescence in situ hybridization (FISH) on metaphase cells.@*RESULTS@#The NIPT test of pregnant women suggested low risk for 21-trisomy, 18-trisomy, and 13-trisomy, whilst indicated the number of chromosome X to be low. The G banded karyotype of the amniotic fluid and cord blood cells was 46,XX. The result of high-throughput sequencing chromosome microdeletion/microduplication detection was seq[hg19](X)× 1, (Y)× 2. FISH showed a clear red signal at each end of a whole chromosome, and a green signal on the other chromosome, with a karyotype of 46,X,ish idic(Y) (q11.23) (SRY++, DXZ1+). C banding showed that there is a dense and a slightly loose centromere at both ends of the Y chromosome, and the parachromatin region was missing. The karyotype of amniotic fluid and cord blood cells was finally determined to be 46,X, pus idic(Y) (q11.23).@*CONCLUSION@#For chromosome anomalies suggested by auxiliary report of NIPT, conventional karyotyping combined with high-throughput sequencing for chromosome microdeletion/microduplication should be adopted for the prevention and reduction of the rate of chromosome microdeletion/microduplication syndromes.

Hemofilia B o enfermedad de Christmas / Hemophilia B or Christmas disease

La hemofilia B o enfermedad de Christmas se diferenció por primera vez de la hemofilia A en 1947. Su forma clásica consiste en un trastorno hereditario de la coagulación causado por mutaciones en el gen F9, que codifica para el factor IX de la coagulación. Su herencia está ligada al cromosoma X; las mujeres son portadoras, pero se manifiesta clínicamente en hombres, aunque se han descrito casos de mujeres portadoras sintomáticas. El factor IX activado es una proteína dependiente de vitamina K, sintetizada en el hígado, que forma parte del complejo tenasa, cuya función es formar la mayor cantidad de trombina en el nuevo modelo de la coagulación basado en células. De acuerdo a la actividad del factor IX, su deficiencia se puede clasificar en leve (5% a 40%), moderada (1% a 5%), o severa (<1%). Su diagnóstico se realiza con la presencia de un TPT alargado que corrige con plasma normal y con la determinación del nivel funcional del factor IX, y se confirma con el estudio molecular que demuestra la mutación en el gen F9. Su diagnóstico diferencial incluye otras patologías como la hemofilia A. El tratamiento con factor IX recombinante es el más utilizado en la actualidad, pero se vienen desarrollando nuevas terapias con virus adeno-asociados recombinantes que prometen mejorar la calidad de vida para algunos pacientes afectados. La profilaxis juega un papel fundamental, en particular en los casos de enfermedad moderada y severa.

Hemophilia B or Christmas disease was first differentiated from hemophilia A in 1947. Its classic form consists of an inherited bleeding disorder caused by mutations in the F9 gene, which codes for coagulation factor IX. Its inheritance is linked to the X chromosome; women are carriers, but it manifests clinically in men, although cases of symptomatic women carriers have been described. Factor IX activates a vitamin K-dependent protein, synthesized in the liver, which is part of the tenase complex whose function is to form the largest amount of thrombin (factor IIa) in the new model of cell-based coagulation. According to factor IX activity, its deficiency can be classified as mild (5% to 40%), moderate (1% to 5%), and severe (<1%). The diagnosis is made when there is a prolonged TPT that corrects with normal plasma, and by assessing the functional level of factor IX. The diagnosis is confirmed by molecular analysis that demonstrates the F9 gene mutation. Its differential diagnosis includes disorders such as hemophilia A. Treatment with recombinant factor IX is widely used, but also new therapies are being developed with recombinant adeno-associated viruses that promise to improve the quality of life for some of these patients. Prophylaxis plays an important role in cases of moderate and severe disease

Trombose arterial recorrente em paciente com doença de Fabry: relato de caso / Recurrent arterial thrombosis in a patient with Fabry disease: case report

Resumo A doença de Fabry é definida como uma doença rara de depósito lisossomal ligada ao cromossomo X que apresenta sintomas multissistêmicos, incluindo comprometimento vascular com eventos trombóticos. Paciente do sexo feminino, 57 anos, com diagnóstico de doença de Fabry há 11 anos, apresentava hiperidrose, hipoacusia e angioqueratoma nas mãos. Na história patológica pregressa, relatou episódio de acidente vascular encefálico isquêmico prévio aos 40 anos de idade e trombose arterial crônica agudizada em membro inferior direito há 1 ano, a qual foi tratada por meio de angioplastia com uso de stent, apresentando melhora temporária e recente recidiva do quadro. Os eventos trombóticos se enquadram nos sintomas típicos da doença de Fabry, e são resultantes do depósito de globotriaosilceramida no endotélio vascular, implicando em um estado pró-trombótico, justificando a reincidência dos sintomas e da trombose arterial em membro inferior.

Abstract Fabry disease is a rare disease, defined as an X-linked lysosomal deposition disease that presents with multisystemic symptoms, including vascular impairment with thrombotic events. A 57-year-old female patient diagnosed with Fabry disease 11 years previously, presented with hyperhidrosis, hypoacusis, and angiokeratoma on the hands. Her previous pathological history included an episode of ischemic stroke before the age of 40 years and chronic acute thrombosis in the right lower limb, 1 year previously, which had been treated with stent angioplasty, with temporary improvement followed by recent relapse of the condition. Thrombotic events fit the typical symptoms of Fabry disease and are caused by deposition of globotriaosylceramide in the vascular endothelium, constituting a prothrombotic state and explaining the recurrence of symptoms and arterial thrombosis in the lower limb.

Parámetros forenses de diez microsatélites del cromosoma X en una muestra de la población del Estado Zulia, Venezuela / Forensic parameters of ten X chromosome microsatellites polymorphisms in a sample of the Zulia State population, Venezuela

Justificación:Las repeticiones cortas en tándem (STRs) están distribuidos por toda la extensión del genoma humano, los ubicados en los cromosomas autosómicos y en el cromosoma Y han sido ampliamente utilizados en los laboratorios de genética forense debido a las características y patrones hereditarios que estos poseen. ObjetivoA fin de caracterizar y determinar parámetros de interés forense en secuencias de tipo STR del cromosoma X (DXS8378, DXS9902, DXS7132, DXS9898, DXS6809, DXS6789, DXS7133, GATA172D05, GATA31E08 y DXS7423) en la población del Estado Zulia.Metodología:Se eligieron 108 individuos (130 cromosomas X),cuyos ADN se amplificaron mediante la reacción en cadena de la polimerasa, los fragmentos se separaron por electroforesis capilar y los alelos reportadoscon respecto a la escalera alélica. Resultados: El contenido de información polimórfica demostró ser mayor de 0,5 en todos los microsatélites y el poder de discriminación acumulado fue de 0,99999997 en mujeres y 0,99999816 en hombres.Conclusiones:Los datos demuestran que los microsatélites del cromosoma X analizados son lo suficientemente informativos como para ser utilizados en casos de vínculos biológicos complejos y la identificación humana...(AU)

Perfil demográfico y epidemiológico de pacientes con Hemofilia y von Willebrand atendidos en el Área de Estomatología del Hospital de Especialidades Carlos Andrade Marín / Demographic and epidemiological profile of patients with Hemophilia and von Willebrand treated in the Stomatology Area of the Carlos Andrade Marín Specialties Hospital

INTRODUCCIÓN. Las alteraciones hereditarias de la hemostasia son patologías raras, dentro de estas se encuentran: Hemofilia A, Hemofilia B y von Willebrand. La hemofilia es un trastorno hereditario, ligado al cromosoma X, causado por ausencia o actividad reducida del factor VIII o IX. La enfermedad de von Willebrand es causada por la deficiencia del factor VIII. OBJETIVO. Determinar el perfil demográfico y epidemiológico de pacientes con Hemofilia y von Willebrand. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, transversal. La población de estudio fueron 133719 con una muestra de 144 pacientes, los criterios de inclusión fueron: pacientes de ambos sexos entre 2 a 88 años de edad, con diagnóstico de Hemofilia A, B, von Willebrand. Atendidos en la consulta externa del Área de Estomatología del Hospital de Especialidades Carlos Andrade Marín, en el periodo 2015-2018. Datos obtenidos del sistema AS400, analizados en el programa International Business Machines Statistical Package for the Social Sciences, Versión 22.0. RESULTADOS. El 77,0% (111; 144) perteneció al género masculino. El rango de edad fue entre 23 y 33 años con 24,0% (34; 144). Tuvieron Hemofilia A 62,0% (93; 144); Hemofilia B 6,0% (9; 144); von Willerbrand 28,0% (42; 144). El 50,0% (77; 144) recibieron tratamientos odontológicos; preventivos 15,0% (21; 144) y curativos 13,0% (18; 144); siendo la mayor patología caries dental. CONCLUSIÓN. Se determinó el perfil demográfico y epidemiológico de los pacientes con Hemofilia y von Willebrand que permitió brindar un tratamiento integral, interdisciplinario y oportuno.

INTRODUCTION. Hereditary abnormalities of hemostasis are rare pathologies, within these are: Hemophilia A, Hemophilia B and von Willebrand. Hemophilia is an inherited disorder, linked to the X chromosome, caused by absence or reduced activity of factor VIII or IX. Von Willebrand's disease is caused by factor VIII deficiency. OBJECTIVE. Determine the demographic and epidemiological profile of patients with hemophilia and von Willebrand. MATERIALS AND METHODS. Observational, descriptive, cross-sectional study. The study population was 133719 with a sample of 144 patients, the inclusion criteria were: patients of both sexes between 2 and 88 years of age, with a diagnosis of Hemophilia A, B, von Willebrand. Attended in the external consultation of the Stomatology Area of the Carlos Andrade Marín Specialty Hospital, in the period 2015-2018. Data obtained from the AS400 system, analyzed in the International Business Machines Statistical Package for the Social Sciences program, Version 22.0. RESULTS 77,0% (111; 144) belonged to the male gender. The age range was between 23 and 33 years with 24,0% (34; 144). They had hemophilia at 62,0% (93; 144); Hemophilia B 6,0% (9; 144); von Willerbrand 28,0% (42; 144). 50,0% (77; 144) received dental treatments; preventive 15,0% (21; 144) and curative 13,0% (18; 144); being the biggest dental caries pathology. CONCLUSION. The demographic and epidemiological profile of patients with Hemophilia and von Willebrand was determined, which allowed to provide a comprehensive, interdisciplinary and timely treatment.

Agammaglobulinemia ligada al cromosoma X, lo crucial del diagnóstico y tratamiento oportunos / Agammaglobulinemia linked to the X chromosome, the crucial of timely diagnosis and treatment

INTRODUCCIÓN. La Agammaglobulinemia ligada al cromosoma X es un tipo de inmunodeficiencia primaria originada por una mutación en el gen que codifica a la proteína responsable del proceso madurativo de los linfocitos B, provocando la disminución o ausencia de inmunoglobulinas en sangre periférica y la predisposición a procesos infecciosos a repetición, sobre todo a nivel del tracto respiratorio y digestivo. La sospecha clínica orienta la solicitud de pruebas complementarias de forma secuencial. El tratamiento consiste en la administración sustitutiva de por vida de inmunoglobulina humana. CASO CLÍNICO. Se presentó el caso de un niño de 8 años de edad con infecciones respiratorias altas y bajas a repetición, con estudios radiográficos de tórax que revelaron una atelectasia persistente, en quien la sospecha clínica dio paso a los evaluativos inmunológico y genético. RESULTADOS. El diagnóstico fue realizado a los 6 años de edad con recuento sérico de inmunoglobulinas por debajo del rango para la edad, citometría de flujo con CD19+ del 0,08% y genética con mutación del gen BTK. Se instauró tratamiento con Inmunoglobulina humana a 400 mg/Kg cada 4 semanas, se monitorizó los niveles de IgG antes de cada infusión. DISCUSIÓN. La Agammaglobulinemia ligada al cromosoma X constituye una enfermedad poco prevalente e infradiagnosticada en la que la sospecha clínica representa la base del abordaje, lo que permitió el tratamiento sustitutivo apropiado. CONCLUSIÓN. El diagnóstico y tratamiento oportunos permitieron evitar el desarrollo de infecciones respiratorias graves, mejorar la calidad de vida del niño y el asesoramiento genético familiar.

INTRODUCTION. X-linked Agammaglobulinemia is a type of primary immunodeficiency caused by a mutation in the gene that encodes the protein responsible for the maturation process of B lymphocytes, causing the decrease or absence of immunoglobulins in peripheral blood and the predisposition to repeated infectious processes, especially at the level of the respiratory and digestive tracts. Clinical suspicion guides the request for complementary tests sequentially. The treatment consists of lifelong substitute administration of human immunoglobulin. CASE REPORT. The case of an 8-year-old boy with repeated high and low respiratory infections was presented, with chest radiographic studies that revealed persistent atelectasis, in whom clinical suspicion gave way to immunological and genetic evaluations. RESULTS. The diagnosis was made at 6 years of age with serum immunoglobulin counts below the age range, flow cytometry with CD19 + of 0,08% and genetics with BTK gene mutation. Treatment with human Immunoglobulin at 400 mg / Kg every 4 weeks was initiated, IgG levels were monitored before each infusion. DISCUSSION. X- linked Agammaglobulinemia is a rare and underdiagnosed disease in which clinical suspicion represents the basis of the approach, which allowed for appropriate replacement. CONCLUSION. Timely diagnosis and treatment allowed to avoid the development of serious respiratory infections, improve de child ́s quality of life and family genetic couseling.

Displasia ectodérmica hipohidrótica tipo 1 ligada al cromosoma X, síndrome de Christ-Siemens-Touraine: caso clínico y revisión de la literatura / Type 1 hypohidrotic ectodermal dysplasia X-linked, the Christ-Siemens-Touraine syndrome: a clinical case and review of the literature

La displasia ectodérmica hipohidrótica tipo 1 ligada al X (DEH1-X) ­síndrome de Christ-Siemens-Touraine­ es una genodermatosis que forma parte de las displasias ectodérmicas, caracterizadas por alteraciones en el desarrollo de una o más estructuras derivadas de ectodermo. Clínicamente presenta hipotricosis, hipohidrosis e hipodontia de severidad variable. Propósito: Describir las características clínicas de la DEH1-X, su manejo odontológico y diferenciarla de otras entidades patológicas. Caso clínico: Paciente masculino de 18 años de edad, con antecedente familiar de displasia ectodérmica hipohidrótica diagnosticada también en un hermano menor. Acude a consulta por prótesis anterior fracturada y mal ajustada. Se trató mediante frenilectomía anterior y rehabilitación bucal protésica. Discusión: En el diagnóstico y tratamiento de las alteraciones congénitas de desarrollo es de particular importancia la identificación temprana y el trabajo en equipo multidisciplinario. El plan de tratamiento y manejo clínico de tejidos orales blandos y duros debe ser adaptado a las necesidades particulares del padecimiento, lo que permitirá establecer un mejor pronóstico. Conclusiones: La DEH1-X es una alteración congénita del desarrollo que afecta estructuras orales, por lo que debe ser identificada por el estomatólogo para atender correctamente las alteraciones dentales y evitar complicaciones posteriores (AU)

Type 1 hypohidrotic ectodermal dysplasia X-linked (DEH1-X) -Christ-Siemens-Touraine syndrome- is a genodermatosis. Ectodermal dysplasias are characterized by development alterations on one or more ectodermal derived structures. IN DEH1-X, patients present hypotrichosis, hypohidrosis and hypodontia of variable severity. Aims: To describe anatomic and clinical characteristics of the DEH1-X, dental treatment, and to differentiate from other clinical conditions. Case report: Male teenager, 18-year-old, was referred for replacement of anterior dental prosthesis. Family history for hypohidrotic ectodermal dysplasia was positive, younger brother with the same condition. Treatment consisted of anterior labial frenectomy and dental prosthetic rehabilitation with acceptable clinical and esthetic's results. Discussion: When diagnosing and treating patients with developmental genetic conditions is particularly important the early detection and the participation of interdisciplinary team work. The clinical treatment of hard and soft tissues of the oral cavity has to be planned and personalized according to the particular needing of each case, in order to achieve better results and long term prognosis. Conclusions: DEH1-X is a congenital developmental disorder, which affects oral structures, should be identified and treated appropriately by the dentist to prevent further dental complications (AU)

Hipoplasia dérmica focal / Focal Dermal Hypoplasia

El síndrome de Goltz llamado también hipoplasia dérmica focal es una rara dermatosis que fue definida por primera vez por Goltz en el año 1962. Se la considera una genodermatosis de presentación esporádica (95% de los pacientes) aunque se han reportado casos de transmisión familiar. Compromete estructuras derivadas del mesodermo y ectodermo con predominio en el sexo femenino acompañada de herencia dominante ligada al cromosoma X. La mutación en el gen PORCN (locus Xp11.23) es letal en la mayoría de varones. La importancia de su publicación radica en su baja frecuencia y las manifestaciones clínicas características que ayudan al establecer el diagnóstico.

Goltz syndrome, also called focal dermal hypoplasia, is a rare dermatosis that was first defined by Goltz in 1962. It is considered a genodermatosis with sporadic presentation (95% of patients) although familiar aggregation has been reported. It compromises mesodermal and ectodermal structures, most frequently in female patients, its inheritance mode is dominant X linked. The mutation in the PORCN gene (locus Xp11.23) is lethal in the majority of males. The importance of its publication lies in its low frequency and clinical characteristic that helps in establishing the correct diagnosis.

Genómica Social: Relaciones entre teoría de la mente y cariotipo en mujeres con diagnóstico de Síndrome de Turner / Social Genomics: Relationships between theory of mind and karyotype in women diagnosed with Turner Syndrome

La teoría de la mente refiere a la capacidad cognitiva de atribuir mente a los demás y de predecir y comprender su comportamiento en términos de entidades mentales como creencias, deseos e intenciones. Investigaciones recientes sugieren una distinción entre una teoría de la mente afectiva y una cognitiva, asignándoles un sustrato neuroanatómico específico. El Síndrome de Turner es un trastorno genético determinado por la deleción total o parcial del cromosoma X en el sexo femenino. Dadas las características biológicas, psicológicas y sociales encontradas en estas mujeres, pueden ser consideradas como una población relevante para el estudio de la teoría de la mente según parámetros biológicos como la expresión diferencial de los genes del cromosoma X. Objetivos y métodos: los objetivos de este estudio fueron describir la teoría de la mente cognitiva y afectiva en 22 mujeres con diagnóstico de Síndrome de Turner y determinar si existen perfiles distintivos de teoría de la mente asociados al cariotipo. Resultados y discusión: Los resultados indicaron que las mujeres con diagnóstico de Síndrome de Turner presentan dificultades generales en teoría de la mente, observándose un menor rendimiento en el aspecto cognitivo de esta capacidad. Asimismo, se encontró que un mayor daño genético se encuentra relacionado a mayores dificultades en la teoría de la mente cognitiva, vinculada a zonas corticales de procesamiento no automático

Theory of mind refers to the cognitive ability to attribute mind to others, and to predict and understand their behavior in terms of mental entities such as beliefs, desires and intentions. Recent research suggests a distinction between an affective and a cognitive theory of mind, assigning a specific neuroanatomical substrate to each one. Turner Syndrome is a genetic disorder that only affects women, and it's determined by a partial or complete deletion of the X-chromosome. Given the biological, psychological and social characteristics found in these women, they can be considered as a relevant population for the study of theory of mind according to biological parameters such as differential expression of the X-chromosome genes. Aims and methods: The aims of this study were to describe cognitive and affective theory of mind in 22 women diagnosed with Turner Syndrome and to determine if there are distinctive theory of mind profiles depending on the karyotype. Results and discussion: Results indicated that women diagnosed with Turner Syndrome present general difficulties in theory of mind, showing a lower performance on the cognitive aspect of this ability. Additionally, evidence was found suggesting that a greater genetic damage is related to greater difficulties in cognitive theory of mind, which is linked to cortical areas of non-automatic processing.

Embryonal Carcinoma of the Pineal Gland Developed in an Adolescent Boy with Klinefelter Syndrome / 임상소아혈액종양

Klinefelter syndrome (KS) is characterized by small testes, gynecomastia, tall stature, and hypergonadotropic hypogonadism. This condition is associated with extra X chromosomes. It is well known that these aneuploidies predispose individuals to the development of several cancers. Moreover, there are many case reports that show KS patients to have a higher relative risk for the development of malignancy. However, incracranial germ cell tumor (ICGCT) associated with KS is very uncommon. Herein, we report delayed diagnosis of KS in a 15-year-old boy with ICGCT, embryonal carcinoma of the pineal gland, after multimodality treatment in Korea.

A case of FLNA gene mutation with respiratory insufficiency and periventricular heterotopia

Filamin A is an actin-binding protein and, in humans, is encoded by FLNA gene in the long arm of X chromosome. Filamin A plays a role in the formation of cytoskeleton by crosslinking actin filaments in cytoplasm. FLNA mutations affect cytoskeletal regulatory processes and cellular migrating abnormalities that result in periventricular heterotopia. A 5-month-old girl was hospitalized because of breathing difficulty and was diagnosed as having periventricular heterotopia with laryngomalacia, cricopharyngeal incoordination, pulmonary hypertension, and chronic lung disease. A genetic test was performed to find the cause of periventricular heterotopia, and FLNA gene mutation (c.5998+1G>A) was confirmed for the first time in Korea. After discharge, she developed respiratory failure due to a viral infection at 8 months of her age. In spite of management with mechanical ventilation, she died of pneumothorax and pulmonary hemorrhage. Herein, we report a case of FLNA gene mutation who presented with periventricular nodular heterotopia with respiratory insufficiency.

Adrenomieloneuropatía, fenotipo de la adrenoleucodistrofia ligada al cromosoma X. Reporte de un caso / Adrenomyeoloneuropathy, X-linked adrenoleukodystrophy phenotype. A Case Report

Introducción: La adrenomieloneuropatía es una enfermedad peroxisomal, con patrón de herencia ligada al sexo. Es una variedad fenotípica de la adrenoleucodistrofia ligada al cromosoma X, esta última es también causa de insuficiencia adrenal. La adrenomieloneuropatía no pura cursa con insuficiencia adrenal. El diagnóstico de la enfermedad se hace por dosificación de ácidos grasos de cadena muy larga en suero. Para el diagnóstico de los fenotipos se emplean datos clínicos, anamnesis, datos de laboratorio y de imagen. Objetivo:Presentar un caso de adrenoleucodistrofia ligada al cromosoma X, fenotipo adrenomieloneuropatía, evaluado por reibergrama. Presentación del caso: Se presenta un caso de adrenomieloneuropatía e insuficiencia adrenal en un paciente masculino de 4 años de evolución, el cual ha sido hospitalizado en el Hospital Clínico-Quirúrgico Dr. Miguel Enríquez de La Habana, Cuba, en 2016 por un proceso respiratorio. Se diagnostica adrenoleucodistrofia ligada al cromosoma X, para identificar las variantes fenotípicas se tuvieron en cuenta los exámenes de laboratorio, técnicas imagenológicas, método clínico y una adecuada anamnesis. Conclusiones: El reibergrama puede contribuir al diagnóstico diferencial entre los fenotipos de la ADL-X y a la comprensión de la respuesta neuroinmunológica en esta enfermedad tal y como se demuestra en este caso(AU)

Introduction: Adrenomyeoloneuropathy is a peroxisomal disease with a sex-linked pattern of inheritance. It is a phenotypic variety of X-linked adrenoleukodystrophy; this last one is also a cause of adrenal insufficiency. Non-pure adrenomyeoloneuropathy occurs with adrenal insufficiency. The diagnosis of the disease is made by dosing very long chain fatty acids in serum. Clinical data, anamnesis, laboratory exams and imaging data are used for the diagnosis of phenotypes. Objective: To present a case of X-linked adrenoleukodystrophy, adrenomyeoloneuropathy phenotype, evaluated by Reibergram. Case presentation: We present a case of adrenomyeoloneuropathy and adrenal insufficiency in a male patient of 4 years of evolution who was admitted to Dr. Miguel Enríquez Clinical and Surgical Hospital, Havana, Cuba, 2016 because he was suffering from a respiratory process. The diagnosis of X-linked adrenoleukodystrophy was made. Laboratory exams, imaging techniques, the clinical method, and an adequate anamnesis were taken into account to for the identification of phenotypic variants. Conclusions: Reibergram can contribute to the differential diagnosis between ADL-X phenotypes and the understanding of the neuroimmunological response in this disease, as it is demonstrated in this case(AU)

Two Korean girls with complete androgen insensitivity syndrome diagnosed in infancy

Androgen insensitivity syndrome (AIS) is a rare genetic disease caused by various abnormalities in the androgen receptor (AR). The AR is an essential steroid hormone receptor that plays a critical role in male sexual differentiation and development and preservation of the male phenotype. Mutations in the AR gene on the X chromosome cause malfunction of the AR so that a 46,XY karyotype male has some physical characteristics of a woman or a full female phenotype. Depending on the phenotype, AIS can be classified as complete, partial or mild. Here, we report 2 cases of complete AIS in young children who showed complete sex reversal from male to female as a result of AR mutations. They had palpable inguinal masses and normal female external genitalia, a blind-end vagina and absent Müllerian duct derivatives. They were both 46,XY karyotype and AR gene analysis demonstrated pathologic mutations in both. Because AIS is inherited in an X-linked recessive manner, we performed genetic analysis of the female family members of each patient and found the same mutation in the mothers of both patients and in the female sibling of case 2. Gonadectomy was performed in both patients to avoid the risk of malignancy in the undescended testicles, and estrogen replacement therapy is planned for their adolescence. Individuals with complete AIS are usually raised as females and need appropriate care.

Resultados audiológicos, complicaciones y experiencia de la cirugía de implante coclear en pacientes con malformación congénita del oído interno tipo partición incompleta tipo III / Audiological results, complications and experience of cochlear implant surgery in patients with congenital malformation of the internal ear type incomplete partition type III

Introducción: La hipoacusia neurosensorial congénita afecta a 1 de cada 1000 recién nacidos vivos, el 50% de estos casos tienen causas genéticas y de estas, entre 1-5% está asociado a alteraciones en el cromosoma X, como lo es la partición incompleta tipo III. Objetivo: Describir la técnica quirúrgica empleada, los resultados funcionales y las complicaciones presentadas durante el periodo pre y post operatorio en un grupo de pacientes pediátricos con diagnóstico radiológico de malformación del oído interno tipo partición incompleta tipo III con seguimiento de 06 meses. Diseño: reporte de casos. Materiales y métodos: Análisis descriptivo de pacientes pediátricos con diagnóstico radiológico de malformación del oído interno tipo partición incompleta tipo III, llevados a cirugía de implante coclear entre Enero de 2015 a Enero de 2017. Resultados: Encontramos 03 pacientes de sexo masculino con edad promedio de 3 años al momento de la cirugía (04 oídos). 01 paciente fue llevado a cirugía de implante coclear bilateral secuencial y dos recibieron implante coclear unilateral. El diagnóstico preoperatorio se realizó apoyado en los hallazgos de Tomografía Computarizada de Alta Resolución y evaluación audiológica preimplante coclear. En 02 pacientes hubo estabilización de la pérdida auditiva en el oído contralateral y recibieron rehabilitación auditiva con audífono convencional. 01 paciente presentó empeoramiento del oído contralateral y requirió cirugía de implante coclear secuencial. Conclusiones: En nuestra experiencia los resultados audiológicos de la cirugía de implante coclear en pacientes con partición incompleta tipo III han sido muy satisfactorios.

Introduction: Congenital sensorineural hearing loss affects one per 1000 live births, 50% of these cases have genetic etiology; and of between them, 1-5% has X chromosome-related causes, an example of this type o disease is the cochlear incomplete partition type III. Objective: To describe the surgical technique used, the functional results and the complications presented during the pre and postoperative period in a group of pediatric patients with radiological diagnosis of inner ear malformation type cochlear incomplete partition type III with follow-up of 06 months. Design: Case report. Materials and methods: A descriptive analysis of pediatric patients with radiological diagnosis of inner ear malformation type incomplete partition type III who were undergone to cochlear implant surgery from 2015/01 to 2017/01 was held. Results: We found 03 male patients with an average age of 3 years at the time of surgery. One patient was undergone to sequential bilateral cochlear implant surgery and two to a unilateral cochlear implant. The preoperative diagnosis was based on the findings of High Resolution Computed Tomography and cochlear preimplantation audiological assessment. In 02 patients there was stabilization of the hearing loss in the contralateral ear and they received hearing rehabilitation with a conventional hearing aid. 01 patient presented worsening of the contralateral ear and required sequential cochlear implant surgery. Conclusions: We recommend hearing rehabilitation with hearing aids or cochlear implant surgery according to the level of hearing loss, avoiding stapes surgery, especially in patients with moderate sensorineural hearing loss, because of a greater risk of higher hearing loss. In our experience, we do not recommend Stapes Surgery as an option for auditory rehabilitation.

Unsettled Issues and Future Directions for Research on Cardiovascular Diseases in Women

Biological sex (being female or male) significantly influences the course of disease. This simple fact must be considered in all cardiovascular diagnosis and therapy. However, major gaps in knowledge about and awareness of cardiovascular disease in women still impede the implementation of sex-specific strategies. Among the gaps are a lack of understanding of the pathophysiology of women-biased coronary artery disease syndromes (spasms, dissections, Takotsubo syndrome), sex differences in cardiomyopathies and heart failure, a higher prevalence of cardiomyopathies with sarcomeric mutations in men, a higher prevalence of heart failure with preserved ejection fraction in women, and sex-specific disease mechanisms, as well as sex differences in sudden cardiac arrest and long QT syndrome. Basic research strategies must do more to include female-specific aspects of disease such as the genetic imbalance of 2 versus one X chromosome and the effects of sex hormones. Drug therapy in women also needs more attention. Furthermore, pregnancy-associated cardiovascular disease must be considered a potential risk factor in women, including pregnancy-related coronary artery dissection, preeclampsia, and peripartum cardiomyopathy. Finally, the sociocultural dimension of gender should be included in research efforts. The organization of gender medicine must be established as a cross-sectional discipline but also as a centered structure with its own research resources, methods, and questions.

Dental Management in a Patient with Turner Syndrome with Dental Anomalies: A Case Report / 대한소아치과학회지

Turner syndrome (TS) is a chromosomal disorder caused by monosomy of the X chromosome, with complete or partial absence of the second sex chromosome. Anomalies of root morphology have been found to occur more often in patients with TS, which make endodontic treatment challenging and requires special handling. The patients with TS may also have systematic problems such as cardiac or renal malformations, so in treating these patients it is important for clinicians not only to be aware of the characteristic intraoral findings, but also to make the patients have regular dental check-ups to prevent oral complications in advance.An 12-year-old girl who had been diagnosed with TS at the age of 10 years was referred due to discomfort in the bilateral mandibular premolar regions. Dens evaginatus and taurodontism were detected in all the mandibular premolars characteristically. The bilateral mandibular first premolars had three roots and the bilateral mandibular second premolars had periapical lesion with two roots. Due to the complexity of the root canal anatomy, root canal treatment were completed with a dental microscope to ensure adequate visualization. After 2 years of regular follow-up examinations, there were no clinical sign or symptom associated with the teeth, and no periapical lesion, was found.This case report describes the characteristic oral features and dental management of TS patients.

Aplicabilidade do cromossomo X no DNA forense / Chromosome X of applicability in DNA forensic

Introdução: os casos de identificação humana com a ausência do pai se tornam de difícil solução com marcadores moleculares autossômicos, do cromossomo Y e situados no DNA mitocondrial. Objetivo: contribuir com a solução destes casos utilizando o polimorfismo genético de marcadores moleculares situados no cromossomo X. Metodologia: buscas foram realizadas em bases de dados nacionais e internacionais até novembro de 2015. Foram selecionados artigos relacionados com o uso de marcadores moleculares e com a solução de casos de paternidade com e sem a ausência do suposto pai. Discussão: os achados na literatura mostram que casos de paternidade com a ausência do pai podem ser solucionados com o polimorfismo do cromossomo X (repetições de tetranucleotídeos), inclusive com menos marcadores em relação às demais classes de marcadores, pois o padrão de herança mostrase diferente entre os pais. Conclusão: a principal aplicabilidade do polimorfismo do cromossomo X situa-se nos casos complexos de identificação humana que não poderiam ser solucionados devido à ausência do material biológico de parentes.

Introduction: cases of human identification, with the father's absence become difficult to solve with autosomal molecular markers of the Y chromosome and located on the mitochondrial DNA. Objective: contribute to the solution of these cases using the genetic polymorphism of molecular markers located on chromosome X. Methodology: searches were carried out in national and international databases until November 2015. We selected articles related to the use of molecular markers and the solution for paternity cases with and without the absence of the alleged father. Discussion: the findings in the literature show that paternity cases with the absence of the father can be solved with the polymorphism of the X chromosome (repeats tetranucleotídeos), including fewer markers in relation to other classes of markers because the inheritance pattern shows different between the parents. Conclusion: the main applicability of X chromosome polymorphism lies in the complex cases of human identification that could not be solved due to the absence of biological material from relatives.