Common Chromosomal Abnormality Research Articles

Morbidity profile of children referred to Genetic Unit of Mansoura University Childrens Hospital, Egypt.

Background: Genetic disorders remain a major cause of morbidity, mortality and handicap in Egypt. This study aims to describe the morbidity pattern of all children with suspected genetic disorders referred to a genetic unit in Egypt. Methods: A retrospective hospital record-based descriptive study was carried out in the Genetic Unit of Mansoura University Children's Hospital, Mansoura, Egypt during a period of 13 years from 2003 up to 2015. The following data was collected for 3197 referred cases: child age at referral, sex, residence and karyotyping results. Results: According to ICD-10 classification of congenital malformations the commonest diagnostic categories are congenital malformations, deformities and chromosomal abnormalities (79.7%) specially chromosomal malformations (73.5%) followed by endocrine, nutritional and metabolic diseases (8.6%), diseases of the nervous system (4.8%), mental and behavioral disorders (3.9%). Mucopolysaccharidosis is the most common type of endocrine, nutritional and metabolic diseases in referred cases. While mental retardation is the commonest mental and behavioral disorders; cerebral palsy and Duchenne muscular dystrophy were the commonest diseases of the nervous system. The commonest congenital malformations of the nervous system are microcephaly and congenital hydrocephalus. Achondroplasia and Osteogenesis imperfect are the most frequent congenital malformations of the musculoskeletal system. Down syndrome is the most common chromosomal abnormality (88.8%) Conclusions: Primary prevention is the most cost effective method for prevention of these disorders. Pre-natal detection of disease should be more available. Educational efforts are needed to increase genetic literacy of the general public and healthcare workers

Down Syndrome child in the Intensive care unit

Down syndrome is the most common chromosomal abnormality in newborns, with a high incidence in Chile. This condition presents unique physiological aspects that should be known, which can affect the child during their stay in an Intensive Care Unit, beyond the neonatal period This review is focused on the respiratory, cardiovascular, infectious and neurological disorders. Anesthetic management and postoperative analgesia considerations, weaning from mechanical ventilation, cervical spine instability and prognosis of the critically ill child with Down syndrome are also analyzed. The evaluation of these conditions should be performed when the patient is admitted to the intensive care unit. The purpose of this update is to update the knowledge of the diagnosis and treatment of potential complications of children with Down syndrome during their stay in the unit of critical patient.

Engineering of Systematic Elimination of a Targeted Chromosome in Human Cells.

Embryonic trisomy leads to abortion or congenital genetic disorders in humans. The most common autosomal chromosome abnormalities are trisomy of chromosomes 13, 18, and 21. Although alteration of gene dosage is thought to contribute to disorders caused by extra copies of chromosomes, genes associated with specific disease phenotypes remain unclear. To generate a normal cell from a trisomic cell as a means of etiological analysis or candidate therapy for trisomy syndromes, we developed a system to eliminate a targeted chromosome from human cells. Chromosome 21 was targeted by integration of a DNA cassette in HeLa cells that harbored three copies of chromosome 21. The DNA cassette included two inverted loxP sites and a herpes simplex virus thymidine kinase (HSV-tk) gene. This system causes missegregation of chromosome 21 after expression of Cre recombinase and subsequently enables the selection of cells lacking the chromosome by culturing in a medium that includes ganciclovir (GCV). Cells harboring only two copies of chromosome 21 were efficiently induced by transfection of a Cre expression vector, indicating that this approach is useful for eliminating a targeted chromosome.

Sperm Retrieval in Patients with Klinefelter Syndrome: A Skewed Regression Model Analysis.

BackgroundThe most common chromosomal abnormality due to non-obstructive azoospermia (NOA) is Klinefelter syndrome (KS) which occurs in 1-1.72 out of 500-1000 male infants. The probability of retrieving sperm as the outcome could be asymmetrically different between patients with and without KS, therefore logistic regression analysis is not a well-qualified test for this type of data. This study has been designed to evaluate skewed regression model analysis for data collected from microsurgical testicular sperm extraction (micro-TESE) among azoospermic patients with and without non-mosaic KS syndrome.Materials and MethodsThis cohort study compared the micro-TESE outcome between 134 men with classic KS and 537 men with NOA and normal karyotype who were referred to Royan Institute between 2009 and 2011. In addition to our main outcome, which was sperm retrieval, we also used logistic and skewed regression analyses to compare the following demographic and hormonal factors: age, level of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone between the two groups.ResultsA comparison of the micro-TESE between the KS and control groups showed a success rate of 28.4% (38/134) for the KS group and 22.2% (119/537) for the control group. In the KS group, a significantly difference (P<0.001) existed between testosterone levels for the successful sperm retrieval group (3.4 ± 0.48 mg/mL) compared to the unsuccessful sperm retrieval group (2.33 ± 0.23 mg/mL). The index for quasi Akaike information criterion (QAIC) had a goodness of fit of 74 for the skewed model which was lower than logistic regression (QAIC=85).ConclusionAccording to the results, skewed regression is more efficient in estimating sperm retrieval success when the data from patients with KS are analyzed. This finding should be investigated by conducting additional studies with different data structures.

Cytogenetic Abnormalities May Predict Transformation to Acute Myeloid Leukemia in Polycythemia Vera Patients

Introduction: Cytogenetic abnormalities can be detected in about 20% of patients with polycythemia vera (PV) at initial diagnosis. The accumulated risk for acute myeloid leukemia (AML) transformation from PV has been estimated to be 2.3-14.4% at 10 years. Risk factors for AML transformation suggested in other studies include older age, abnormal karyotype and high leukocyte count. The purpose of this study is to evaluate the association of cytogenetic abnormalities with AML transformation in PV.Methods: We searched the database at our institution for patients with a diagnosis of PV during Jan. 1994 to Apr. 2015. Demographic data, clinical presentations and follow-up, and laboratory data including karyotype before and after AML transformation were collected. Bone marrow morphology, especially evidence of myelodysplasia, myelofibrosis and blast percentage were evaluated.Results: A total of 317 patients with a diagnosis of PV were identified. 36 (11%) patients progressed to AML (Group A), including 15 who presented in chronic phase and 21 in blast phase. The median interval from the diagnosis of PV to AML transformation was 97 months (range, 11 - 331 months). For comparison, 50 patients with similar demographic features during the same time interval but no evidence of AML transformation were also included in the study (Group B). The age of patients in both groups was comparable (median age: 57 vs. 54 years, p=0.2791). All patients were positive for JAK2 V617F mutation. The main therapies for patients with chronic phase PV included phlebotomy, hydrea, and tyrosine kinase inhibitors in a small subset of patients. There was no significant difference of treatments among the patients in groups A and B.Karyotype at chronic phase of PV was available in 15 patients in Group A and all 50 patients in Group B. Eleven (73%) patients in Group A showed an abnormal karyotype in chronic phase. The most common chromosomal abnormalities were trisomy 1q (n=6, 40%), including 4 (27%) patients with [+1, der(1;7)(q10;p10)] resulting in trisomy 1q and del(7q); and complex karyotype (n=3, 20%). Del(20q) and +8 was uncommon, only detected in 1 patient each. In Group B, 11 (22%) patients had an abnormal karyotype, which was much less frequent compared with Group A. No patients in Group B showed a complex karyotype or trisomy 1q; instead, del(20q) (n=6, 55%), +9 and/or +8 (n=5, 45%) were the most common chromosomes abnormalities detected.The median follow-up was 10 years in Group A and 14.5 years in Group B. At the time of AML transformation, 35 (97%) patients in Group A showed an abnormal karyotype, including 21 (58%) patients with a complex karyotype, 22 patients with -5/del(5q) and/or -7/del(7q) and 10 (28%) with trisomy 1q [8 with +1, der(1;7)]. Among the 15 patients who had karyotypic information during the chronic phase, 4 (27%) patients showed clonal evolution and 7 (47%) acquired new unrelated abnormal clones when AML transformation occurred.Morphologically, 15 patients in Group A had sequential bone marrow evaluation from chronic phase to blast phase, 14 (93%) patients developed myelofibrosis and 7 (47%) patients showed multilineage dysplasia during the chronic phase. At the time of AML transformation, 35 (97%) patients showed myelodysplasia. In Group B, 5 (10%) patients developed myelodysplasia and 31(62%) developed myelofibrosis in follow-up bone marrow samples.Conclusion: Cytogenetic abnormalities are associated with AML transformation in PV patients. Patients with an abnormal karyotype, especially with abnormalities of trisomy 1q [+1,der(1;7)(q10;p10)] or a complex karyotype, are at highest risk to develop clonal evolution or acquire new myelodysplasia-related clones [like -5/del(5q) and/or -7/del(7q)] or develop myelodysplasia and transform into AML. On the other hand, cytogenetic abnormalities, such as del(20q), +8 and/or +9, although commonly detected in PV, are associated with a low risk for myelodysplasia and AML transformation. Surveillance for cytogenetic abnormalities is helpful in the risk assessment of AML transformation in PV patients. DisclosuresNo relevant conflicts of interest to declare.

Deletion of PTPN1 Promotes the Development of Myelofibrosis

Deletion of chromosome 20q [del(20q)] is a common chromosomal abnormality associated with myeloid neoplasms including myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS), MDS/MPN overlap disorders and acute myeloid leukemia (AML). The del(20q) lesion is often associated with myeloproliferative features; it is present in patients with myelofibrosis (MF) at a high frequency (24%) and thus considered to be one of the most frequent cytogenetic abnormalities in MF (Wassie et al., Br J Haematol. 2015). The del(20q) lesion can also coexist with JAK2V617F mutation in MPN/MF. However, the target tumor-suppressor gene(s) within chromosome 20q involved in the pathogenesis of MF remains unknown.The PTPN1 locus maps to human chromosome 20q13.1-q13.2. PTPN1 (also known as PTP1B) is a ubiquitously expressed non-receptor tyrosine phosphatase that has been linked to metabolism and cancer. Mice deficient in Ptpn1 exhibit resistance to diet-induced obesity and diabetes. Both oncogenic and tumor suppressor functions for PTPN1 have been suggested. PTPN1 can negatively regulate the JAK/STAT signaling, which is frequently found activated in MPN.Here, we report the identification and functional consequences of PTPN1 deletion in the pathogenesis of MF. Deletion of PTPN1 was identified in 14% cases of MF. Conditional deletion of Ptpn1 in the mouse hematopoietic compartment resulted in significant increases in white blood cell and neutrophil counts in the peripheral blood and enlargement of spleen size. Flow cytometric analyses showed significant expansion of myeloid (Gr-1+/Mac-1+) precursors in the bone marrow (BM) and spleens of Ptpn1-deleted mice compared with control animals. Megakaryocytic (CD41+/CD61+) precursors were also significantly increased in the spleens of Ptpn1-deleted mice. Flow cytometric analyses also revealed significant increases in absolute numbers of LSK cells (Lin-Sca1+c-kit+) and its subsets including long-term hematopoietic stem cells (LT-HSC), short-term HSC (ST-HSC) and multi-potent progenitors (MPP) in the spleens of Ptpn1-deleted mice. Hematopoietic progenitor colony assays showed significant increases in myeloid (CFU-GM) and megakaryocytic (CFU-Mk) colonies in the BM of Ptpn1-deleted mice compared with control mice BM. Histopathologic analysis demonstrated fibrosis (grade 2) in the BM and spleens of Ptpn1-deleted mice at 52 weeks after induction, whereas control animals did not exhibit fibrosis at that age. Together, these results suggest that deletion of Ptpn1 induces an MPN-like phenotype, which progresses to MF over time. Moreover, transplantation of Ptpn1-deficient BM into lethally irradiated wild-type animals resulted in fibrosis at 18 weeks after transplantation, demonstrating that the effect of Ptpn1 loss in the development of myelofibrosis is cell-intrinsic. Competitive repopulation assays using BM from control or Ptpn1-deficient (CD45.2+) mice with wild type congenic (CD45.1+) mice showed that deletion of Ptpn1 enhances the repopulation capacity of hematopoietic stem cells. Biochemical analyses revealed that depletion of Ptpn1 enhanced JAK2/STAT5, AKT and ERK signaling in the BM of Ptpn1-deleted mice. Furthermore, we observed that deletion of Ptpn1 in Jak2V617F knock-in mice accelerates the development of myelofibrosis. In conclusion, our results establish a tumor-suppressor function for PTPN1 in MF. DisclosuresNo relevant conflicts of interest to declare.

Prenatal cytogenetic diagnosis in Taiwan: a nationwide population-based study

Purpose: The goal of this study was to gain a better understanding of the status of advanced maternal age among criteria for provision of amniocentesis in pregnant women in Taiwan.Materials and method: Data of 315 670 second-trimester amniocenteses from 28 national certified cytogenetics laboratories were retrospectively analyzed from the Prenatal Genetic Diagnosis Declaring and Database System of the Health Promotion Administration, Ministry of Health and Welfare in Taiwan between 2006 and 2013.Results: The number of pregnant women undergoing amniocentesis in Taiwan between 2006 and 2013 increased, and the most common three indications for amniocentesis were advance maternal age (75.11%), abnormal second trimester maternal serum screening (13.22%) and abnormal sonographic finding (8.00%). Down syndrome was the most common autosomal abnormality identified (25.74%); Turner syndrome was the most common sex chromosome abnormality (7.04%). Of structural rearrangements, 26.93% were balanced translocations and 17.10% were unbalanced translocations. The greatest proportion of fetal chromosomal abnormalities was found in cases where parents were also affected (38.02%).Conclusions: Clinical workers should provide detailed genetic diagnostic information to pregnant women, especially those with the common amniocentesis indications, which will enable them to determine a birth plan.

Expression patterns of the chromosome 21 MicroRNA cluster (miR-99a, miR-125b and let-7c) in chorioamniotic membranes

Trisomy 21 (T21) is the most common chromosome abnormality in humans and is associated with a spectrum of phenotypes, including cognitive impairment, congenital heart defects and immune system defects. In addition, T21 is also associated with abnormalities of fetal membranes including chorioamniotic separation, delayed fusion of the chorioamniotic membranes, defects in syncytiotrophoblast formation, as well as amniocyte senescence. There is evidence indicating miRNAs encoded by sequences on chromosome 21 (Chr-21) are involved in several of the cognitive and neurological phenotypes of T21, but the role of Chr-21 derived miRNAs in fetal membrane abnormalities associated with T21 has not been investigated. In the current study, we determined the expression patterns of three miRNAs derived from a cluster on Chr-21 – hsa-miR-99a, hsa-miR-125b and hsa-let-7c in chorioamniotic membranes obtained from term pregnancies with spontaneous rupture (n = 20). Tissue and location specific expression patterns within the chorioamniotic membranes were identified. The rupture zone in the choriodecidua had distinct expression patterns compared to other fetal membrane locations. Despite the increased gene dosage associated with T21, the expression of all three miRNAs was reduced in cultured T21 amniocytes as compared to cultured euploid amniocytes. In silico analysis of experimentally validated targets of the three miRNAs suggest these Chr-21 derived miRNAs play a potential role in fetal membrane rupture and the fetal membrane defects associated with T21.

Tobacco Smoke and Ras Mutations Among Latino and Non-Latino Children with Acute Lymphoblastic Leukemia

Childhood acute lymphoblastic leukemia (ALL) is a biologically heterogeneous disease, and mutations in the KRAS and NRAS oncogenes are present at diagnosis in about one-fifth of cases. Ras mutations were previously associated with environmental exposures in leukemias as well as in many other cancer types. This study examined whether Ras mutation could define a unique etiologic group of childhood ALL associated with tobacco smoke, a well-established mutagen and carcinogen. We included 670 children with ALL enrolled in a case-control study in California (1995-2013), including 50.6% Latinos. Parental and child exposure to tobacco smoke was obtained from interviews. Sanger sequencing was used to detect the common KRAS and NRAS hotspot mutations in diagnostic bone marrow DNA. ALL cases were also characterized for common chromosome abnormalities. In case-case analyses, logistic regression analyses were used to estimate odds ratios to describe the association between tobacco smoke exposure and childhood ALL with Ras mutations. KRAS or NRAS mutations were detected in ∼18% of children diagnosed with ALL. Ras mutations were more common among Latino cases compared with non-Latino whites and in high-hyperdiploid ALL. No associations were observed between parental smoking or child's passive exposure to smoke and Ras positive ALL. The apparent lack of association between tobacco smoke and Ras mutation in childhood ALL suggests that Ras mutations do not specifically define a tobacco-related etiologic pathway. Reasons for racial and ethnic differences in ALL are not well understood and could reflect differences in etiology that warrant further examination.

Correlation analysis between ultrasound findings and abnormal karyotypes in the embryos from early pregnancy loss after in vitro fertilization-embryo transfer.

The purpose of the study is to evaluate the correlation between ultrasound findings and abnormal karyotypes in early pregnancy losses (EPLs) after in vitro fertilization-embryo transfer (IVF-ET). This retrospective analysis assessed 2172 cases of EPL after IVF-ET occurring between January 2008 and December 2013. The cases were examined via transvaginal ultrasonography (TVS). Embryonic tissue karyotyping following miscarriage was performed using a comparative genomic hybridization (CGH) analysis with fluorescence in situ hybridization (FISH). The correlations between the ultrasound findings and the karyotypes were evaluated. Six categories of ultrasound findings were observed: normal ultrasound, empty sac, yolk sac only, small gestational sac, small embryonic pole, and early symmetrical arrested growth. The overall rate of abnormal karyotypes was 44.9% (976/2172), and the rate of abnormal karyotypes associated with a normal ultrasound, empty sac, yolk sac only, small gestational sac, small embryonic pole, and early symmetrical arrested growth was 49.5% (218/440), 28.1% (138/491), 43.4% (197/454), 50.0% (43/86), 49.8% (155/311), and 57.7% (225/390), respectively. Compared with the other groups, the prevalence of chromosomal abnormalities was significantly higher in the early symmetrical arrested growth group but was markedly lower in the empty sac group in all cases and when cases of 46,XX were excluded (p < 0.05). Trisomy 16 was the most common chromosomal abnormality in the yolk sac only, small embryonic pole and early symmetrical arrested growth groups. In the empty sac, small gestational sac and normal ultrasound groups, monosomy X was the most frequent abnormality. Chromosomal anomalies may be associated with specific types of ultrasound findings in EPLs after IVF-ET.

Sexual dysfunction in Klinefelter's syndrome patients.

Klinefelter's syndrome (KS) is the most common chromosomal abnormality in men with infertility and hypogonadism. Although its influence on fertility has been extensively investigated, very few studies assessed the sexual function of patients with KS. Our aim was to assess the prevalence of sexual dysfunction in patients with KS and investigate possible aetiological factors for reported findings. Medical records of 53 patients with KS were retrospectively reviewed and compared to 75 age-matched control subjects who were prospectively recruited. Sexual history was evaluated through utilisation of international index of erectile function-5 and Arabic index for premature ejaculation questionnaires. Sexual desire was reported subjectively by patients or controls. The incidence of erectile dysfunction and premature ejaculation in patients with KS was 18.9% and 22.6% respectively. Compared to age-matched controls, patients with KS had significantly lower incidence of PE. However, there was no statistically significant difference between both groups regarding erectile function. Libido was significantly lower in patients with KS than normal controls (54.7% vs. 17.3%, p=0.001). Klinefelter's syndrome is a condition that has a variable presentation. Despite having a higher likelihood of reduced sexual desire, patients may have normal erectile function comparable to age-matched individuals. They tend to have a lower incidence of premature ejaculation.

Association of Turner syndrome and GH deficiency

Introduction Turner syndrome (TS) represents one of the most common chromosomal abnormalities in females. It is associated with a wide spectrum of clinical features, such as gonadal dysgenesis and short stature. Short stature in TS is usually not attributed to growth hormone deficiency (GHD). The aim of our study was to report 4 cases with TS and GHD. Methodology It is a retrospective study including 4 patients with TS. GHD was confirmed by failure of GH to raise more than 10 ng/mL after L-dopa stimulating test and insulin induced hypoglycemia test. Results All patients were referred to our department with a delayed puberty and short stature. The mean age at the diagnosis of TS was 18.5 ± 2.4 years. Physical examination revealed dysmorphic syndrome in all patients. The mean height was 1.37 ± 0.06 m ( Conclusion GHD is not a common finding in patients with TS. It should be considered only when the short stature is lower than that usually found in TS.

Cytogenetics in the management of acute myeloid leukemia: an update by the Groupe francophone de cytogénétique hématologique (GFCH).

The karyotype is critical for the evaluation of acute myeloid leukemia (AML) at diagnosis. Cytogenetic abnormalities detected in AML are one of the most powerful independent prognostic factors. It impacts on the choice of treatment in clinical trials. All chromosomes can be targeted, common chromosomal abnormalities are recurrent and may be associated with a cytological well-defined type. In 40% of the cases, the karyotype is normal and must be associated with molecular biology studies that can refine the prognosis. The usefulness of the karyotype is more limited during the follow-up of the patient due to its limited sensitivity, but it is still useful in the clinical management of relapse. Since 2001, the WHO (World Health Organization) classification of hematological malignancies integrates cytogenetic data in the classification of AML. Karyotype is therefore mandatory in the diagnosis of AML.

Prenatal decision-making in the second and third trimester in trisomy 21-affected pregnancies.

Down syndrome (DS) is the most common chromosome abnormality among live-born infants and the most frequent genetic cause of intellectual disability. The majority of pregnancies affected by DS are terminated. The decision concerning whether or not to continue a pregnancy following the prenatal diagnosis of DS is complex and amongst others, motivated by attitudes towards termination, socioeconomic factors, and ultrasound findings. In Germany, termination of pregnancy (TOP) is a legal option, even during the later stages of gestation. The aim of the present study was to evaluate the pregnancy outcomes as well as possible factors that influence the decisions made by women with trisomy 21-affected pregnancies. In our study 112 pregnancies affected by trisomy 21 were included. Our data confirm that most patients are more likely to terminate a trisomy 21-affected pregnancy [76 (67.9%) vs. 36 (32.1%) continued pregnancies]. Beyond that we found that women who continued their pregnancy tended to be at an advanced stage in their pregnancy at the time of karyotyping. With regards to factors from their medical history as well as sonographic findings there was no identifiable single factor that could distinguish between women that opted to continue or terminate their pregnancy.

TLE4 regulation of wnt-mediated inflammation underlies its role as a tumor suppressor in myeloid leukemia

The presence of AML1-ETO (RUNX1-CBF2T1), a fusion oncoprotein resulting from a t(8;21) chromosomal translocation, has been implicated as a necessary but insufficient event in the development of a subset of acute myeloid leukemias (AML). While AML1-ETO prolongs survival and inhibits differentiation of hematopoietic stem cells (HSC), other contributory events are needed for cell proliferation and leukemogenesis. We have postulated that specific tumor suppressor genes keep the leukemic potential of AML1-ETO in check. In studying del(9q), one of the most common concomitant chromosomal abnormalities with t(8;21), we identified the loss of an apparent tumor suppressor, TLE4, that appears to cooperate with AML1-ETO to confer a leukemic phenotype. This study sought to identify the molecular basis of this cooperation. We show that the loss of TLE4 confers proliferative advantage to leukemic cells, simultaneous with an upregulation of a pro- inflammatory signature mediated through aberrant increases in Wnt signaling activity. We further demonstrate that inhibition of cyclooxygenase (COX) activity partly reverses the pro-leukemic phenotype due to TLE4 knockdown, pointing towards a novel therapeutic approach for myeloid leukemia.

Newly emerged isolated Del(7q) in patients with prior cytotoxic therapies may not always be associated with therapy-related myeloid neoplasms

Deletion 7q is a common chromosomal abnormality in myeloid neoplasms. Detection of del(7q) in patients following cytotoxic therapies is highly suggestive of an emerging therapy-related myeloid neoplasm. In this study, we describe 39 patients who acquired del(7q) as a sole abnormality in their bone marrow following cytotoxic therapies for malignant neoplasms. The median interval from cytotoxic therapies to detection of del(7q) was 40 months (range, 4–190 months). Twenty-eight patients showed an interstitial and 11 showed a terminal 7q deletion. Fifteen patients (38%) had del(7q) as a large clone and 24 (62%) as a small clone. With a median follow-up of 21 months (range, 1–135 months), 18 (46%) patients developed therapy-related myeloid neoplasms, including all 15 patients with a large del(7q) clone and 3/24 (12.5%) with a small clone. Of the remaining 21 patients with a small del(7q) clone, 16 showed no evidence of therapy-related myeloid neoplasms and 5 had an inconclusive pathological diagnosis. We conclude that isolated del(7q) emerging in patients after cytotoxic therapy may not always be associated with therapy-related myeloid neoplasms in about half of patients. The clone size of del(7q) is critical; a large clone is almost always associated with therapy-related myeloid neoplasms, whereas a small clone can be a clinically indolent or transient finding.

Respiratory manifestations of Down syndrome

Down syndrome - the most common human congenital disease, the most common chromosomal abnormality (trisomy of chromosome 21). In addition to the phenotypic features of multiple anomalies on the part of the cardiovascular, central nervous and immune systems, gastrointestinal, musculoskeletal system, is very common in patients with Down syndrome are diseases of the respiratory tract. The article presents current data from the literature on the causes of recurrent respiratory infections, obstruction of the upper and lower respiratory tract infections, obstructive sleep apnea associated with phenotypic characteristics of children, predisposing to obstruction. The data on the consequences of such abnormalities of the respiratory tract as a tracheal bronchus. Detailed description of interstitial lung disease in Down syndrome that can develop as a primary pathological process or be the result of infectious lesions and aspiration. Computed tomography allows visualization of pulmonary disorders architectonic, perilobulyarnye shading, depletion of lung pattern at the level of segments and subpleural cysts, the diagnosis of which is of great importance due to the high risk of pneumothorax. We discuss the etiology of the structural changes in the lung, their relationship with pulmonary hypoplasia and congenital heart disease. It is emphasized that the assessment of biopsies morphologists in Down syndrome is complex, as there are multiple, overlapping lung damage. Powered by observation of the patient with Down syndrome and subpleural cysts in the lungs. Thus, patients with Down syndrome have a variety of respiratory symptoms, the possibility of these lesions should be considered in the management of patients.

76. Profile and spectrum of congenital heart defect in pediatric patient with down syndrome

Down syndrome is one of the most common chromosomal abnormality worldwide. It occurs in 1 of every 800 live births. Almost one-half of patients with Down Syndrome have congenital heart defect. Our objective is to describe the frequency and spectrum of congenital heart defect (CHD) among children with Down Syndrome in Saudi Arabia and identify the rate of primary and secondary pulmonary hypertension among pediatric patients with Down syndrome. Cross-sectional, retrospective study of the cardiac anomalies among 331 pediatric patients (0–18 years) with Down Syndrome in King Khalid University Hospital (KKUH) from August 2001 till October 2014. The demographic data, reason for referral, echocardiography data including systolic function parameters, the presence of CHD, type and details of CHD, presence of pulmonary hypertension (PHTN), history of cardiac surgeries or transcatheter interventions. Among the 331 pediatric patients with Down Syndrome; 230 patients (69.5%) have Congenital Heart Defect (CHD). The patients with CHD were significantly younger (median age 3 months) with lower weight ( P -value P -value P -value

A multicenter study of fetal chromosomal abnormalities in Chinese women of advanced maternal age

ObjectiveThis study aimed to determine the rates of different fetal chromosomal abnormalities among women of advanced maternal age in China and to discuss the possible misdiagnosis risks of newer molecular techniques, for selection of appropriate prenatal screening and diagnostic technologies. Materials and MethodsSecond trimester amniocentesis and fetal karyotype results of 46,258 women were retrospectively reviewed. All women were ≥ 35 years old with singleton pregnancies. The rates of clinically significant chromosomal abnormalities (CSCAs), incidence of chromosomal abnormalities, and correlations with age were determined. ResultsFrom 2001 to 2010, the proportion of women of advanced maternal age undergoing prenatal diagnosis increased from 20% to 46%. The mean age was 37.4 years (range, 35–46 years). A total of 708 cases of CSCAs, with a rate of 1.53% were found. Trisomy 21 was the most common single chromosome abnormality and accounted for 55.9% of all CSCAs with an incidence of 0.86%. Trisomy 13, trisomy 18, and trisomy 21, the most common chromosome autosomal aneuploidies, accounted for 73.6% of all CSCAs, with a rate of 1.13%. As a group, the most common chromosomal aneuploidies (13/18/21/X/Y) accounted for 93.9% of all abnormalities, with a rate of 1.44%. The incidence of trisomy 21, trisomy 13/18/21 as a group, and 13/18/21/X/Y as a group was significantly greater in women aged 39 years and older (p < 0.001), but was not different between women aged 35 years, 36 years, 37 years, and 38 years. ConclusionThese findings may assist in genetic counseling of advanced maternal age pregnant women, and provide a basis for the selection of prenatal screening and diagnostic technologies.

Cytogenetic profiles of 2806 patients with acute myeloid leukemia-a retrospective multicenter nationwide study.

The cytogenetic and molecular data is recognized as the most valuable prognostic factor in acute myeloid leukemia (AML). Our aim was to systemically analyze the cytogenetics of Korean AML patients and to compare the cytogenetic profiles of various races to identify possible geographic heterogeneity. We retrospectively reviewed medical records of 2806 AML patients diagnosed at 11 tertiary teaching hospitals in Korea between January 2007 and December 2011. The most common recurrent chromosomal abnormality was t(8;21) (8.8%, 238/2717), but t(15;17) showed an almost same number (8.6%,235/2717). Among de novo AML, the most frequent aberrations were t(15;17), observed in 229 (10.7%). The most common French-American-British (FAB) classification type was M2 (32.2%), and recurrent cytogenetic abnormalities correlated with the FAB subtypes. Among 283 secondary AML cases, myelodysplastic syndrome was the most common predisposing factor. About 67.1% of the secondary AML cases were associated with chromosomal aberrations, and chromosome 7 abnormalities (n = 45, 15.9%) were most common. The incidence of FLT3 internal tandem duplication mutation was relatively low at 15%. Our study reports certain similarities and differences in comparison to previous reports. Such discrepancies call for extensive epidemiological studies to clarify the role of genetic as well as geographic heterogeneity in the pathogenesis of AML.