Síndrome de Klinefelter, testosterona y sueño: a propósito de un caso clínico / Klinefelter's syndrome, testosterone and sleep: a clinical case

Se presenta un caso clínico de Síndrome de Klinefelter y se revisan que los aspectos en relación al sueño en estos pacientes, siendo relevante a ser abordado y estudiado debido a la relación causal entre el metabolismo de esteroides sexuales afectados. En especial la testosterona y cómo esto influye en la microarquitectura del sueño y la probabilidad de presentar síndrome de apnea obstructiva del sueño, con las repercusiones cognitivas que pueden sumarse a las ya descritas por el síndrome en si. De allí la importancia de un seguimiento y abordaje dirigido en este aspecto, al momento del diagnóstico y en el seguimiento a largo plazo.

A clinical case of Klinefelter's Syndrome is presented and the aspects related to sleep in these patients are reviewed, being relevant to be addressed and studied due to the causal relationship between the metabolism of affected sex steroids, especially testosterone and how this influences the microarchitecture of sleep and the probability of presenting obstructive sleep apnea syndrome with the cognitive repercussions that can be added to those already described by the syndrome itself. Hence the importance of a targeted follow-up and approach in this aspect, at the time of diagnosis and in long-term follow-up.

Triglyceride-glucose index levels in patients with Klinefelter syndrome and its relationship with endothelial dysfunction and insulin resistance: a cross-sectional observational study.

Objective: This study aimed to investigate the triglyceride-glucose (TyG) index, which is a simple surrogate marker of insulin resistance that is associated with various cardiometabolic diseases, in patients with Klinefelter syndrome (KS). Subjects and methods: A total of 30 patients with KS (mean age: 21.53 ± 1.66 years) and 32 healthy controls (mean age: 22.07 ± 1.01 years) were included in the study. The clinical and laboratory parameters, TyG index, asymmetric dimethylarginine (ADMA) level, homeostatic model assessment of insulin resistance (HOMA-IR) score, and high-sensitivity C-reactive protein level were measured in patients with KS and healthy subjects. Results: Patients with KS had higher HOMA-IR score (p = 0.043), ADMA levels (p < 0.001), and TyG index (p = 0.031) and lower high-density lipoprotein cholesterol levels (p < 0.001) than healthy subjects. TyG index was positively correlated with plasma ADMA (r = 0.48, p < 0.001) and HOMA-IR (r = 0.36, p = 0.011). Multivariate analyses showed that total testosterone level (ß = -0.44, p = 0.001) and TyG index (ß = 0.29, p = 0.045) were independent determinants of plasma ADMA levels. Conclusion: Patients with KS had higher TyG indices than healthy subjects. Moreover, TyG index was independently associated with endothelial dysfunction in patients. TyG index may be a practical and useful measure to show the increased endothelial dysfunction in patients with KS.

Reconsidering the olfactory and brain structures in Kallmann's syndrome: New findings in the analysis of volumetry.

OBJECTIVE: Kallmann's syndrome (KS) is characterized by hypogonadotropic hypogonadism and olfactory disorders. The complementary exams for evaluating of patients with hypogonadotrophic hypogonadism are important for the diagnosis and management of these patients. PATIENTS: We performed a well-established olfactory Sniffin' Stick test (SST) on 17 adult patients with KS and brain magnetic resonance imaging (MRI) to evaluate olfactory structures and further analysis by Freesurfer, a software for segmentation and volumetric evaluation of brain structures. We compared the Freesurfer results with 34 healthy patients matched for age and sex and performed correlations between the data studied. RESULTS: More than half of the patients with KS reported preserved smell but had olfactory disorders in the SST. In the MRI, 16 patients showed changes in the olfactory groove, the olfactory bulb-tract complex was altered in all of them and 52% had symmetrical structural changes. Interestingly, the pituitary gland was normal in only 29%. Regarding correlations, symmetrical changes in the olfactory structures were related to anosmia in 100%, while asymmetric changes induced anosmia in only 50% (p = .0294). In Freesurfer's assessment, patients with KS, compared to controls, had lower brainstem volume. In those with aplastic anterior olfactory sulcus, the brainstem volume was lower than in hypoplasia (p = .0333). CONCLUSIONS: Olfactory assessment and MRI proved to be important auxiliary tools for the diagnosis and management of patients with KS. New studies are needed to confirm the decrease in brainstem volume found by the Freesurfer software in patients with KS. Further studies are needed to confirm the decrease in brainstem volume found by the Freesurfer software in patients with KS.

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.

Clinical and laboratory differences between chromosomal and undefined causes of non-obstructive azoospermia: A retrospective study.

BACKGROUND: Knowledge of clinical and laboratory differences between chromosomal and undefined causes aids etiological research on non-obstructive azoospermia. OBJECTIVE: Compare clinical and laboratory differences between men with non-obstructive azoospermia due to chromosomal anomalies versus undefined causes. DESIGN AND SETTING: A cross-sectional retrospective study conducted at a public university hospital in Campinas (Brazil). METHODS: All men aged 20-40 years with non-obstructive azoospermia were included in the analysis. RESULTS: The 107 cases included 14 with Klinefelter syndrome (KS) (13%), 1 with mosaic KS, 4 with sex development disorders (2 testicular XX, 1 NR5A1 gene mutation, and 1 mild androgen insensitivity syndrome) (4%), 9 with other non-obstructive azoospermia etiologies (8%), and 79 with undefined causes. The 22 chromosomal anomaly cases (14 KS, 1 mosaic KS, 2 testicular XX, 4 sex chromosome anomalies, and 1 autosomal anomaly) were compared with the 79 undefined cause cases. The KS group had lower average testicular volume, shorter penile length, and lower total testosterone levels but greater height, arm span, serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and gynecomastia frequency (absent in the undefined group and affecting more than half of the KS group). Patients with testicular XX DSD had LH, FSH, and penile length data intermediate between the KS and undefined cause groups, testicular volume similar to the KS group, and other data similar to the undefined group. CONCLUSION: Clinical and laboratory data differentiate men with non-obstructive azoospermia and chromosomal anomalies, particularly KS and testicular XX, from those with undefined causes or other chromosomal anomalies.

Pulmonary Thromboendarterectomy in Klinefelter Syndrome. Literature Review.

Klinefelter syndrome  is a form of male hypogonadism due to testicular sclerohyalinosis with atrophy and azoospermia, which is the most common cause of male infertility. The syndrome is usually accompanied by metabolic, morphological, and neurobehavioral manifestations; Venous thromboembolic diseases such as deep vein thrombosis and pulmonary embolism. The existence of chronic thromboembolic pulmonary hypertension in patients with Klinefelter syndrome   is scarce in the literature. We present the imaging and genetic analysis of a 37 -year-old male with a history of deep vein thrombosis who was admitted for exertional dyspnea.

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

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

Cariótipos possíveis na síndrome de Klinefelter: uma revisão narrativa / Possible karyotypes in the syndrome Klinefelter: A Narrative Review

Os sinais clínicos da síndrome de Klinefelter foram observados pela primeira vez em 1942, mas sua etiologia só foi definida em 1959. Trata-se de uma condição genética na qual pelo menos um cromossomo X extra é adicionado ao cariótipo masculino normal (46,XY) e acomete cerca de 1 em cada 500 homens. É caracterizada por variabilidade fenotípica que leva a atraso ou ausência de diagnóstico, com uma estimativa de 50% a 75% de homens com Síndrome de Klinefelter nunca obterem o diagnóstico correto. Apesar de o cariótipo clássico (47,XXY) ser encontrado em 80%-90% dos pacientes e o mosaicismo (46,XY/47,XXY) nos 10% restantes, outros cariótipos podem ser encontrados menos frequentemente. Nesse sentido, este estudo tem por finalidade descrever os possíveis cariótipos identificados nos pacientes com Síndrome de Klinefelter. Os resultados mostram que a Síndrome de Klinefelter é usualmente diagnosticada na vida adulta e caracterizada por uma heterogeneidade citogenética quanto aos cariótipos possíveis apresentados pelos pacientes afetados. A condição foi diagnosticada precocemente quando associada à anomalia dos cromossomos autossomos, excesso de cromossomos X extra ou quando foi realizado diagnóstico pré-natal por idade materna avançada. É imprescindível que os profissionais de saúde, em especial os médicos, se familiarizem mais com essa condição, pois o diagnóstico correto e precoce permite a intervenção e tratamento adequados visando melhorar a qualidade de vida desses indivíduos.

Identification of common differentially expressed genes in Turner (45,X) and Klinefelter (47,XXY) syndromes using bioinformatics analysis.

BACKGROUND: Analysis of patients with chromosomal abnormalities, including Turner syndrome and Klinefelter syndrome, has highlighted the importance of X-linked gene dosage as a contributing factor for disease susceptibility. Escape from X-inactivation and X-linked imprinting can result in transcriptional differences between normal men and women as well as in patients with sex chromosome abnormalities. OBJECTIVE: To identify differentially expressed genes among patients with Turner (45,X) and Klinefelter (46,XXY) syndrome using bioinformatics analysis. METHODOLOGY: Two gene expression data sets of Turner (45,X) and Klinefelter syndrome (47,XXY) were obtained from the Gene Omnibus Expression (GEO) database of the National Center for Biotechnology Information (NCBI). Statistical analysis was performed using R Bioconductor libraries. Differentially expressed genes (DEGs) were determined using significance analysis of microarray (SAM). The functional annotation of the DEGs was performed with DAVID v6.8 (The Database for Annotation, Visualization, and Integrated Discovery). RESULTS: There are no genes over-expressed simultaneously in both diseases. However, when crossing the list of under-expressed genes for 45,X cells and the list of over-expressed genes for 47,XXY cells, there are 16 common genes: SLC25A6, AKAP17A, ASMTL, KDM5C, KDM6A, ATRX, CSF2RA, DHRSX, CD99, ZBED1, EIF1AX, MVB12B, SMC1A, P2RY8, DOCK7, DDX3X, eight of which are involved in the regulation of gene expression by epigenetic mechanisms, regulation of splicing processes and protein synthesis. CONCLUSION: Of the 16 identified as under-expressed in 45,X cells and over-expressed in 47,XXY cells, 14 are located in X chromosome and 2 in autosomal chromosome; 8 of these genes are involved in the regulation of gene expression: 5 genes are related to epigenetic mechanisms, 2 in regulation of splicing processes, and 1 in the protein synthesis process. Our results are limited by it being the product of a bioinformatic analysis from mRNA isolated from whole blood, this makes necessary further exploration of the relationships between these genes and Turner syndrome and Klinefelter syndrome in the future.

Genital malformation: Trigger of the diagnosis of severe variants of Klinefelter syndrome. / Malformación genital: Disparador del diagnóstico de variantes severas de síndrome de Klinefelter.

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

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

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

Androgen Treatment in Adolescent Males With Hypogonadism.

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

Cytogenetic assessment of Iranian infertile men with undescended testis: A retrospective study.

OBJECTIVE: Undescended testis (UDT) is a urogenital disease that affects fertility. This study looked into the cytogenetic abnormalities of Iranian infertile patients with UDT. METHODS: Our study included 522 infertile patients with UDT (case group) and two control groups, one with 300 infertile men without UDT and another with 268 fertile men. RESULTS: Chromosomal abnormalities were found in 45 patients with UDT (8.62%). Seven of the alterations were considered as normal features. Klinefelter syndrome and mosaicism were the most common anomalies. Chromosomal abnormalities were found in 31 infertile men in the control group (10.33%), 13 of which deemed normal and 18 (6%) anomalous. Nine chromosomal abnormalities were found in the second control group with fertile men (3.35%), six deemed normal and three (1.11%) anomalous. CONCLUSION: Despite the high rate of abnormalities in infertile controls (6%) and the higher rate seen in infertile individuals with UDT indicate a significant prevalence of chromosomal abnormalities in the Iranian population, particularly when the literature suggests that the normal rate of abnormal karyotypes should be within the 0.7-1% range in the general population. The incidence of abnormal karyotypes increased when infertile patients had additional conditions such as UDT.

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

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

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

[Thymoma in a patient with klinefelter syndrome. Case report]. / Síndrome de Klinefelter diagnosticado en un adulto a raíz del estudio de infección respiratoria recurrente y masa mediastínica. Caso clínico.

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

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

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

Down-Klinefelter syndrome (48,XXY,+21) in a neonate associated with congenital heart disease.

Double aneuploidy is considered a rare phenomenon. Herein, we describe a case of double aneuploidy 48,XXY,+21 in a neonate with congenital heart defects. The 28-day-old neonate male (23-year-old mother and 24-year-old father) was admitted to a neonatal intensive care unit owing to congenital heart disease. Echocardiography showed a complete atrioventricular septal defect with Rastelli type B and significant left ventricular failure, moderate atrioventricular valve regurgitation, right-sided heart failure, and preserved systolic function. Cytogenetic analysis of the newborn showed double aneuploidy 48,XXY,+21. The maternal karyotype was 46,XX,inv(9)(p11q13) and the paternal was 46,XY. Characteristics associated with Down syndrome are observed in newborns; on the other hand, children under 10 months of age and neonates may show little or no signs of the Klinefelter syndrome. According to this study, there seem to be differences between the frequency of congenital heart disease among patients with Down-Klinefelter and Down syndrome. At about 11 months of age, the child died after undergoing heart surgeries. The early cytogenetic study is important for better diagnosis and management of the disease.