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The genetics of Down syndrome (DS) and Klinefelter syndrome (KS) are a nondisjunction of autosomal and sex chromosomes, respectively, resulting in aneuploidies. Less than 70 cases of concurrent Down-Klinefelter syndrome (DS-KS) have been reported in the literature. We report the case of a five-month-old Indian child with a rare double aneuploidy resulting in DS-KS. A five-month-old boy born to non-consanguineously married parents presented with failure to thrive and dysmorphic facies. The family history was unremarkable. On examination, he had an upward eye slant, a depressed nasal bridge, a horizontal crease in the left hand, and a sandal gap. A clinical diagnosis of the Down phenotype was considered. Karyotype analysis revealed the presence of double aneuploidy (48, XXY,+21) suggestive of DS-KS. Down-Klinefelter syndrome presents with the DS phenotype at birth, and the characteristic KS phenotype develops in early infancy and apparently manifests during puberty only. Early diagnosis is required for parental counseling and planning for future pregnancies. In children with a typical Down syndrome phenotype, chromosomal analysis is highly recommended. The diagnosis of DS-KS at the earliest has implications for these children's short-term and long-term outcomes. It helps in planning the subsequent pregnancy with appropriate genetic testing and counseling to avoid the risk of another child with trisomy.

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Introduction and importance: Edward syndrome is a severe chromosomal defect that occurs as a result of non-disjunction through meiosis. It presents with cardiac septal defects, horseshoe kidneys, patent ductus arteriosus, central nervous system dysgenesis, distinctive craniofacial deformities, and overriding or overlapping fingers. Klinefelter syndrome (47, XXY) is found in 1 in 660 newborn males. It is considered to be one of the most common genetic causes of infertility. It manifests with small firm testes, androgen insufficiency, and azoospermia. Case presentation: A 2-month-old male infant with a history of weakness in feeding, frequent convulsions, and an increase in cyanosis two days ago. There were multiple skeletal deformities and a tendency to spasm in the extremities, left ventricular atrophy, mitral atresia, atrial septal defect, ventricular septal defect with dilated right cavities, tricuspid valve regurgitation, pulmonary valve stenosis; and the aorta exits in the right ventricle. There is a widening of the subdural space, which was observed in the left frontal-parietal side with cortical atrophy in that area and a widening of the Sylvian fissure. A karyotype test confirmed the presence of Edward and Klinefelter syndromes. Clinical discussion: Aneuploidy is a chromosomal issue characterized by an abnormal number of a chromosome copies. The coexistence of two aneuploidies is called "double aneuploidy" which is a rare occurrence. Herein, we report a case of a 2-month-old male with Edward syndrome and Klinefelter syndrome. Conclusion: This publication aims to highlight the challenges in diagnosing and treating a complicated genetic disease.

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Down syndrome (DS, trisomy 21) with an extra copy of chromosome 21 is one of the most common aneuploidies in humans. Jacobs syndrome or XYY syndrome (trisomy XYY) with an extra copy of sex chromosome Y is a rare sex chromosome trisomy in males. Double aneuploidy (DA) with an extra copy of chromosome 21 and sex chromosome Y is an extremely rare occurrence. Most trisomy 21 results from nondisjunction during maternal oocyte meiosis-I, whereas trisomy XYY is results from nondisjunction during paternal spermatocyte meiosis-I. We present a case of natural conception premature newborn of 30.4 weeks gestational age who had a DS facial phenotype with extensive syndactyly on both hands and feet. Other multisystem congenital anomalies were discovered, including mal-aligned perimembranous ventricular septal defect, bicuspid aortic valve, Dandy-Walker malformation's tetra-ventriculomegaly, and a rare complete tracheal rings deformity (CTRD) with trachea stenosis. Prenatal amniocentesis and postnatal chromosomal karyotyping analysis detected 48, XYY, + 21 nontranslocation trisomy 21, and free-lying Y chromosome without translocation. The existence of DA is rarely reported in literature reviews. In this review, we will discuss the characteristics of DS and Jacobs syndrome as well as the associated multiorgan malformation including the rare lethal CTRD.

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This retrospective study was performed on 208 patients with Down syndrome (DS) from heterogeneous ethnic population and admitted under Genetics Metabolic Unit. The aim of the study was to look for phenotypic variability and associated complications in children and adolescents with DS. The average age of the evaluated DS patients was 34 months. Cardiac anomalies were found in 128 (62%) of the 208 cases. Among the cardiac disorders, atrial septal defects accounted for 30% of cases. Other complications observed were hypothyroidism and developmental delay in around 31% cases and neonatal cholestasis in 14% cases. Also, we report two cases with Moya-Moya disease and one case with atlanto-axial dislocation.

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Double aneuploidies, such as Down syndrome and sex chromosome aneuploidies, are relatively rare. One rare form of double aneuploidy, Down-Klinefelter syndrome, is described here. The phenotypic characteristics of a three-year-old child showed the presence of features typical of Down syndrome. He had a global developmental delay, small testes, and diabetes mellitus by 18 months of age. Regardless of the presenting clinical features, karyotyping should be performed in all patients with suspected Down syndrome. In Down-Klinefelter syndrome, anticipatory phenotype goes beyond the sum of individual syndromic characteristics.

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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.

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BACKGROUND: Double aneuploidy is common, especially in products of conception, frequently involving a combination of a sex chromosome and an acrocentric chromosome. Double autosomal trisomies are rare with only five cases reported. Double aneuploidy mosaicism involving two different cell lines is rarer with only three cases reported. CASE PRESENTATION: We report a fourth case of double aneuploidy mosaicism on a baby. Results of a 24-h preliminary chromosome analysis at birth showed a mosaic karyotype, 47,XX,+18[15]/47,XX,+21[8]/48,XX,+21,+mar[7]. Reflex testing to SNP microarray with the same sample collected at birth showed gain of a 77.9 Mb region on chromosome 18 and gain of a 32.5 Mb region on chromosome 21. Microarray did not show any other copy number variants indicating that the marker chromosome may not contain any euchromatic material. A repeat chromosome analysis at 1-year of age showed a mosaic karyotype, 47,XX,+18[76]/47,XX,+21[4] with loss of the marker cell line. CONCLUSION: Based on our results, we propose that the mosaic double autosomal trisomy in our case was due to two independent non-disjunction events in a normal zygote very early during embryogenesis.

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Transient abnormal myelopoiesis (TAM) is a unique neonatal leukemoid reaction caused by a pathognomonic GATA1 mutation in conjunction with the gene dosage effect of trisomy 21, which is either of germline or somatic origin. We encountered a 48,XYY,+21 phenotypically normal neonate with Down syndrome who developed TAM due to cryptic germline mosaicism. Quantification of the mosaic ratio was complicated by an overestimation bias of hyperproliferating TAM within the germline component. To establish a workflow for such a clinical scenario, we analyzed the cytogenetic findings of neonates with TAM associated with somatic or low-level germline mosaicism. We showed that multistep diagnostic procedures (i.e., paired cytogenetic analyses of peripheral blood specimens in culture with or without phytohemagglutinin; serial cytogenetic studies of more than one tissue, such as the buccal membrane; and complementary DNA-based GATA1 mutation screening) can verify the specificity of cytogenetic testing for phenotypically normal neonates with TAM suspected of mosaicism.

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Double trisomy 48, XXY, +21 or Down-Klinefelter syndrome is a rare occurrence and presents clinical manifestation of trisomy 21 in early life and of Klinefelter syndrome after 10 months of age. The phenotypic and karyotyping characteristics of a 2-month-old boy were reported. He had mild clinical feature of Down syndrome and echocardiographic features of atrioventricular (AV) septal defects with severe pulmonary valve stenosis.

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Aneuploidy mosaicism involving two complementary different autosomal trisomy cell lines is extremely rare. Although a mosaic double trisomy 8/trisomy 21 has been described in literature, this is the first report of Warkany (+8)-Down (+21) syndrome due to two complementary mosaic trisomy cell lines. The phenotype of the male patient with Warkany-Down syndrome includes upslanting palpebral fissures, hypertelorism, small low-set ears with unilateral aural stenosis, large and broad hands and feet with deep palmar and plantar creases, bilateral cryptorchidism, generalized mild hypotonia and transient neonatal thrombocytopenia. At the age of two years, his developmental quotient is around 50. His height, weight and head circumference are below the third centile. We speculate on the mechanism of origin of the complementary trisomy cell lines based on molecular cytogenetic studies that showed no evidence for a chimera.

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BACKGROUND: Double aneuploidies - especially in combination with structural aberrations - are extremely rare among liveborns. The most frequent association is that of Down (DS) and Klinefelter syndromes (KS). We present the case of a male newborn with a unique 47,XY,+ 21[80%]/48,XY,+i(X)(q10),+ 21[20%] karyotype, hypothesize about his future phenotype, discuss the aspects of management and review the literature. CASE PRESENTATION: The additional association of isochromosome Xq (i(X)(q10)) could be the result of a threefold non-disjunction event. 47,XY,+i(X)(q10) KS is not common and its symptoms differ from the classical KS phenotype. In combined DS and i(X)(q10) KS, the anticipatory phenotype is not simply the sum of the individual syndromic characteristics. This genotype is associated with higher risk for several diseases and certain conditions with more pronounced appearance: emotional and behavioral disorders; poorer mental and physical quality of life; lower muscle mass/tone/strength; connective tissue weakness; muscle hypotonia and feeding difficulties; osteopenia/-porosis with earlier beginning and faster progression; different types of congenital heart diseases; more common occurrence of hypertension; increased susceptibility to infections and female predominant autoimmune diseases; higher risk for hematological malignancies and testicular tumors. CONCLUSIONS: In multiple aneuploidies, the alterations have the potential to weaken or enhance each other, or they may not have modifying effects at all. Prenatal ultrasound signs are not obligatory symptoms of numerous chromosomal anomalies (specifically those involving supernumerary sex chromosomes), therefore combined prenatal screening has pertinence in uncomplicated pregnancies as well.

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In the present paper, we report two rare cases of Down syndrome (DS); mosaic Down-Turner syndrome and DS with rob (13;14). Patient 1 karyotype is mos 45,X[41] / 47, XX,+21[59] and patient 2 karyotype is 46, XY, rob (13;14)(q10;q10),+21. With these two unusual cases, we aimed to look at the most common numerical and structural chromosome anomalies from a different window and evaluate the phenotypic effect in the presence of different chromosomal anomalies. Our main goal is to evaluate the phenotypic characteristics of these two rare variants in the light of literature.

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@#Individuals with double aneuploidy of Down-Turner syndrome are very rare and to date, fewer than 50 cases have been reported, worlwide. We report a case of a male infant who presented with dysmorphic features of upslanting eyes, flat nasal bridge, wide spaced nipples and macroglossia. Based on the clinical features, he was diagnosed with Down syndrome. His peripheral blood sample was taken and sent for cytogenetic analysis for confirmation. Chromosome analysis of his lymphocyte cell culture revealed a mosaic pattern of double aneuploidy with monosomy X identified in 31 metaphases and trisomy 21 in 14 metaphases: (45,X[31]/47,XY,+21[14]). Further analysis with fluorescence in situ hybridization (FISH) using Vysis LSI SRY Spectrum Orange/CEP X Spectrum Green Probe and Vysis CEP Y Spectrum Aqua Probe and Vysis LSI 21 Spectrum Orange Probe performed on the cells (nuclei and metaphases) has confirmed the presence of the abnormal two cell lines (81% monosomy X and 19% trisomy 21) in the patient. Ultrasound investigations of his pelvic region showed normal testes and no evidence of uterus, ovary or vagina. To the best of our knowledge, this is the first Down-Turner syndrome reported in Malaysia. In conclusion, this case demonstrates the importance of Giemsa-banded karyotype and FISH analyses as diagnostic tools in identifying the chromosomal abnormality and determining the ratio of the normal:abnormal cells present in the patient. An annotated bibliography of earlier reported cases of Down-Turner with documented karyotyping is also included in this report.

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

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

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

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

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En los síndromes Down (SD) y Klinefelter (SK) independientes entre si, ambas aneuploidías cromosómicas son causadas por exceso. La ocurrencia de estas dos alteraciones en un individuo es un fenómeno relativamente raro. En casos de doble aneuploidiìa donde están involucrados autosomas y cromosomas sexuales, predominan las manifestaciones clínicas relacionadas con los autosomas y se solapan las de cromosomas sexuales. Caso clínico: se trata de un paciente de dos anÞos de edad, con signos sugerentes de SD, producto del tercer embarazo de una madre de 32 anÞos. Examen físico: braquicefalia, perfil plano, hipertelorismo, desviación de las hendiduras palpebrales, orejas de baja implantación, prominencia de la sutura metópica, paladar alto y estrecho, cuello corto, diaìstasis de músculos rectos anteriores, hernia umbilical, braquidactilia, línea de Sydney en mano derecha, micro pene, hipotonía moderada. El estudio citogenético evidencio una formula cromosómica 48,XXY,+21,der(X) para el caso y 46,XX,del(Xp)(p11.3-pter) en la madre. Con esto se logró precisar una correlación genotipo-fenotipo que nos confirma el diagnóstico de síndrome Down-Klinefelter con deleción p11.3-pter de cromosoma X heredado de la madre. Las manifestaciones fenotípicas del SK solapadas por una aneuploidiìa autosómica deben evaluarse detenidamente en la pubertad.

In Down Syndrome (DS) and Klinefelter Syndrome (KS) independent of one another, both chromosome aneuploidies are caused by excess. The occurrence of these alterations in one individual is a relatively rare phenomenon. In cases of double aneuploidy in which autosomes and sex chromosomes are involved, the predominant clinical manifestations are related to autosomes and the alterations due to sex chromosomes overlap. Clinical case: The patient is a two year old boy, with signs suggestive of DS, product of the third pregnancy of a mother of 32 years of age. Physical exam: brachycephaly, flat facial profile, hypertelorism, upslanting palpebral fissures, low-set ears, prominent metopic suture, high and narrow palate, short neck, diastasis recti, umbilical hernia, brachydactyly, Sydney line in the right hand, micro pennies, moderate hypotonia. The cytogenetic study revealed a chromosomal formula 48,XXY,+21,der(X) in the case and 46,XX,del(Xp)(pter-p11.3) in the mother, which specifies a genotype-phenotype correlation and confirms the diagnosis of Down- Klinefelter Syndrome with deletion p11.3-pter of X chromosome inherited from the mother. The phenotypic manifestations of KS overlapped by an autosomal aneuploidy should be carefully assessed at puberty.

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Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5-year-old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management.

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A neonate with a double aneuploidy associated with congenital heart defect (CHD) suffered from cyanosis after birth. He had typical features of Down syndrome (DS) including hypertelorism, slightly lowset ears with protruding pinna. Doppler echocardiography indicated complex congenital heart disease with an ostium secundum atrial septal defect, enlarged right ventricle, and mild tricuspid valve regurgitation. Further chromosomal analysis showed a karyotype of 48,XXY,+21: a double aneuploidy of DS and Klinefelter syndrome (KS). Until now, only seven cases of double aneuploidy associated with CHD defect have been reported.

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We report the case of a 3-yr-old boy with Down-Turner mosaicism and review the previous reports of Down-Turner syndrome with documented karyotyping and clinical features. The patient showed clinical features of Down syndrome without significant stigma of Turner syndrome. Cytogenetic analysis of peripheral blood preparations by using G-banding revealed mosaicism with 2 cell lines (45,X[29]/47,XY,+21[4]). FISH analysis revealed that 87.5% of the cells had monosomy X karyotype and 12.5% of the cells had XY karyotype; trisomy 21 was only detected in the Y-positive cells. We suggest that additional cells should be analyzed and molecular genetic studies should be conducted to rule out double aneuploidy when karyotypes with sex chromosome aneuploidies and mosaicism are encountered, as in our case of Down syndrome mosaic with sex chromosome aneuploidy.

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