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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: This publication aims to highlight the challenges in diagnosing and treating a complicated genetic disease.

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.

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.

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.

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.

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.
METHODS: 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.
CONCLUSIONS: 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.

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.

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.

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.