Anomalies in Down syndrome individuals in a large population‐based registry

Torfs, Claudine P.; Christianson, Roberta E.

doi:10.1002/(sici)1096-8628(19980605)77:5<431::aid-ajmg15>3.3.co;2-q

Cited by 77 publications

(131 citation statements)

References 22 publications

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“…The mapping of the triplicated genomic segment of chromosome 21 that harbors the functional elements contributing to congenital heart defect (CHD) 46,47 is of importance to understand the pathogenesis of these anomalies. CHD is present in only 2/12 (17%) compared to the overall risk of CHD of 40% reported in DS patients.…”

Section: Partial Trisomy 21 and Critical Regionsmentioning

confidence: 99%

Genotype–phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21

et al. 2008

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Down syndrome (DS) is one of the most frequent congenital birth defects, and the most common genetic cause of mental retardation. In most cases, DS results from the presence of an extra copy of chromosome 21. DS has a complex phenotype, and a major goal of DS research is to identify genotype -phenotype correlations. Cases of partial trisomy 21 and other HSA21 rearrangements associated with DS features could identify genomic regions associated with specific phenotypes. We have developed a BAC array spanning HSA21q and used array comparative genome hybridization (aCGH) to enable high-resolution mapping of pathogenic partial aneuploidies and unbalanced translocations involving HSA21. We report the identification and mapping of 30 pathogenic chromosomal aberrations of HSA21 consisting of 19 partial trisomies and 11 partial monosomies for different segments of HSA21. The breakpoints have been mapped to within B85 kb. The majority of the breakpoints (26 of 30) for the partial aneuploidies map within a 10-Mb region. Our data argue against a single DS critical region. We identify susceptibility regions for 25 phenotypes for DS and 27 regions for monosomy 21. However, most of these regions are still broad, and more cases are needed to narrow down the phenotypic maps to a reasonable number of candidate genomic elements per phenotype.

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Section: Partial Trisomy 21 and Critical Regionsmentioning

confidence: 99%

Genotype–phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21

et al. 2008

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“…Sites abstracted infant records and entered the information onto a structured clinical form, which was then reviewed by a Table 1 Population-based studies of congenital heart defects in down syndrome Freeman et al 2 and unpublished Kallen et al 3 Stoll et al 4 Torfs and Christianson 5 Current study single clinically trained individual at Emory. The presence or absence of CHDs, the particular heart defect(s) diagnosed, and the date and method(s) of diagnosis were recorded for each infant.…”

Section: Clinical Informationmentioning

confidence: 99%

“…In 1998 the Atlanta Down syndrome Project (ADSP), a forerunner of the NDSP, reported that 41% of newborns with DS were born with one or more major heart defects, including atrioventricular septal defect (AVSD), secundum atrial septal defect (ASDII), ventricular septal defect (VSD), and tetralogy of Fallot (TOF). 2 Findings from the ADSP and other recent population-based studies of DS and CHDs [2][3][4][5] are summarized in Table 1.…”

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confidence: 99%

Ethnicity, sex, and the incidence of congenital heart defects: a report from the National Down Syndrome Project

Freeman

Bean

Allen

et al. 2008

Genetics in Medicine

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Purpose: The population-based National Down Syndrome Project combined epidemiological and molecular methods to study congenital heart defects in Down syndrome. Methods: Between 2000 and 2004, six sites collected DNA, clinical, and epidemiological information on parents and infants. We used logistic regression to examine factors associated with the most common Down syndrome-associated heart defects. Results: Of 1469 eligible infants, major cardiac defects were present in 44%; atrioventricular septal defect (39%), secundum atrial septal defect (42%), ventricular septal defect (43%), and tetralogy of Fallot (6%). Atrioventricular septal defects showed the most significant sex and ethnic differences with twice as many affected females (odds ratio, 1.93; 95% confidence interval, 1.40 -2.67) and, compared with whites, twice as many blacks (odds ratio, 2.06; 95% confidence interval, 1.32-3.21) and half as many Hispanics (odds ratio, 0.48; 95% confidence interval, 0.30 -0.77). No associations were found with origin of the nondisjunction error or with the presence of gastrointestinal defects. Conclusions: Sex and ethnic differences exist for atrioventricular septal defects in Down syndrome.Identification of genetic and environmental risk factors associated with these differences is essential to our understanding of the etiology of congenital heart defects. The National Down Syndrome Project (NDSP) seeks to investigate the etiology and phenotypic consequences of trisomy 21 Down syndrome (DS). 1 Aside from the universal findings of mental retardation and hypotonia, congenital heart defects (CHDs) are arguably the most important clinical sequelae of an extra chromosome 21. In 1998 the Atlanta Down syndrome Project (ADSP), a forerunner of the NDSP, reported that 41% of newborns with DS were born with one or more major heart defects, including atrioventricular septal defect (AVSD), secundum atrial septal defect (ASDII), ventricular septal defect (VSD), and tetralogy of Fallot (TOF). 2 Findings from the ADSP and other recent population-based studies of DS and CHDs 2-5 are summarized in Table 1.With the birth prevalence of major DS-associated CHDs well established by multiple studies using modern diagnostic methods, attention can now be directed toward understanding the etiology of these defects. Not only do infants with DS have a higher rate of CHDs than do infants without DS, but one defect, the AVSD, is particularly characteristic. To understand the etiology of CHDs in DS and of AVSD specifically, both genetic and environmental determinants must be explored. For example, several recent reports have suggested that the distribution of CHDs in DS varies by ethnicity (race/ethnicity), 6 -13 but most population-based studies have not had broad ethnic representation (Table 1). Drawing on our experience with the ADSP, we designed the multicenter NDSP to explore possible CHD risk factors singly and in combination. The NDSP is one of the largest population-based studies of CHDs in DS and the first to assemble clinical, demographic, a...

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“…It occurs in about 1 in 700 births, and is more common in males [1]. Most children are diagnosed on basis of phenotypic findings like, flat nasal bridge, poor muscle tone, a small head, upward slanting eyes, epicanthal folds, small ears, small mouth, dermographics (ulner loops, single palmer crease, and distal tri-radii), clinodactyly, large tongue, and a large space between toes (sandal gap).…”

Section: Introductionmentioning

confidence: 99%

Consanguinity and pattern of congenital heart defects in Down syndrome in Kashmir, India

Ashraf¹,

Malla²

2010

AJSIR

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Anomalies in Down syndrome individuals in a large population‐based registry

Cited by 77 publications

References 22 publications

Genotype–phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21

Genotype–phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21

Ethnicity, sex, and the incidence of congenital heart defects: a report from the National Down Syndrome Project

Consanguinity and pattern of congenital heart defects in Down syndrome in Kashmir, India

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