Genotype-phenotype correlation for congenital heart disease in Down syndrome through analysis of partial trisomy 21 cases

Background: Down syndrome or trisomy 21 is one of the most common chromosomal disorders with moderate intellectual disability. In addition to mental retardation, this syndrome is associated with different congenital anomalies and characteristic dysmorphic features. Affected individuals are more susceptible to congenital heart disease and digestive anomalies, pulmonary complications, immune and endocrine system disorders. While several international studies have shown association of co-morbidities with trisomy 21, there is insufficient data available in Bangladesh.The present study aimed to evaluate the associated co-morbidities in children with Down syndrome. Methods: A cross-sectional study was conducted among pediatric cases with Down syndrome who attended the endocrine outpatient department (OPD) of BIRDEM General Hospital from June 2006 to December 2016. The cases were diagnosed either by Karyotyping or by characteristic phenotypes.The clinical and laboratory data of the patients were collected from outpatient history records for analysis. Results: There were total 42 children with Down syndrome, with mean age 4.2 years at assessment and female predominance (1.47:1). Thyroid dysfunction was the most common (69%) followed by congenital heart disease (57%). Among the thyroid disorders, acquired hypothyroidism was found in 55% cases, congenital hypothyroidism in 41% cases and only one had hyperthyroidism. Isolated patent ductus arteriosus (PDA) and atrial septal defect (ASD) comprised the commonest single congenital heart disease found in 53% and combined atrioventricular septal defect was the commonest among complex congenital cardiac defect observed in our study. Both thyroid dysfunction and congenital heart disease were found more in female children with Down syndrome than their male counterpart and it was found statistically significant. Fifty percent of our Down syndrome cases were referred from other healthcare centers to address developmental delay. Conclusion: Hypothyroidism and congenital heart disease are frequently associated in Down syndrome children in Bangladesh. This calls for developing awareness among health professionals to diagnose comorbidities at an early stage and to form recommendations for long term follow up. BIRDEM Med J 2021; 11(3): 191-196

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Genotype-phenotype correlation in congenital heart disease

Current Opinion in Cardiology ◽

10.1097/00001573-200405000-00006 ◽

2004 ◽

Vol 19 (3) ◽

pp. 221-227 ◽

Cited By ~ 6

Author(s):

Mark B. Lewin ◽

Ian A. Glass ◽

Patricia Power

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Congenital Heart ◽

Phenotype Correlation ◽

Genotype Phenotype Correlation

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In Utero Diagnoses of Strikingly Similar Presentations of Complete Atrioventricular Septal Defects in a Pair of Dizygotic Twins Concordant for Trisomy 21

Case Reports in Pediatrics ◽

10.1155/2018/6215675 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5

Author(s):

Diamond Ling ◽

Jonathan G Dayan

Keyword(s):

Congenital Heart Disease ◽

Down Syndrome ◽

Heart Disease ◽

Trisomy 21 ◽

Maternal Age ◽

Congenital Heart ◽

Genetic Disorder ◽

Advanced Maternal Age ◽

Dizygotic Twins ◽

Increased Risk

Trisomy 21, or Down syndrome (DS), is a genetic disorder affecting approximately 1 in 500–750 live births. The prevalence of DS has increased over the past two decades, correlating with a rise in the proportion of pregnancies complicated by advanced maternal age. There is also a correlation between advanced maternal age and dizygotic twinning rates. There is an increased risk of at least one twin being affected in dizygotic pregnancies compared to singletons. However, despite this greater relative risk, reports of concordance of DS in both dizygotic twins are very rare. Congenital heart disease (CHD) occurs in roughly 40% of individuals with DS, but there can be considerable phenotypic variation. The most common, atrioventricular septal defect accounts for only 40% of CHD seen in DS. There is also a higher incidence of CHD in twins, but also with a low incidence of concordance. There have been only five reported cases of concordant DS in dizygotic twins with confirmed chromosomal analyses; none of which describe concordant congenital heart disease. Here, we describe an unusual case of dizygotic twins of differing genders concordant for both Down syndrome and congenital heart disease of a strikingly similar presentation.

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Early Prenatal Diagnosis of an Extremely Rare Association of Down Syndrome and Transposition of the Great Vessels

Revista de Chimie ◽

10.37358/rc.19.7.7383 ◽

2019 ◽

Vol 70 (7) ◽

pp. 2574-2578

Author(s):

Cristina Crenguta Albu ◽

Dinu-Florin Albu ◽

Stefan-Dimitrie Albu ◽

Anca Patrascu ◽

Ana-Roxana Musat ◽

...

Keyword(s):

Congenital Heart Disease ◽

Down Syndrome ◽

Heart Disease ◽

Prenatal Diagnosis ◽

Trisomy 21 ◽

Congenital Heart ◽

Heart Defects ◽

Live Births ◽

Cardiac Malformations ◽

Great Vessels

Every year, an estimated 7.9 million infants (6% of worldwide births) are born with serious�birth defects [1].�Congenital cardiovascular defects make up one of the largest groups of severe congenital malformations [2].The incidence of congenital heart defects in different studies varies from about 4/1,000 to 50/1,000 live births [3].� Congenital heart disease is frequently described in patients with Down syndrome and is the main cause of death in this population during the first two years of life [4].�Trisomy 21 with cardiovascular malformations have a maternal age-adjusted regional prevalence of 4.33/10,000 for the white population and 3.70/10,000 for the nonwhite population [5].�Prenatal diagnosis of�congenital�heart disease is important for proper perinatal and neonatal management, as congenital cardiac malformations occurs in approximately eight of 1000 live births [6]. We present an extremely rare case of early prenatal diagnosis and management of a fetus with trisomy 21 associated with the transposition of the great vessels, one of the most mysterious congenital cardiac malformations.

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Pattern of congenital heart diseases among children with Down syndrome attending a tertiary care medical college hospital

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20172665 ◽

2017 ◽

Vol 4 (4) ◽

pp. 1357

Author(s):

Kumar G. V. ◽

Srinivasa V. ◽

Ananda kumar T. S.

Keyword(s):

Congenital Heart Disease ◽

Down Syndrome ◽

Heart Disease ◽

Chromosomal Abnormality ◽

Trisomy 21 ◽

Congenital Heart ◽

Heart Diseases ◽

Tertiary Care ◽

Congenital Heart Diseases ◽

Increased Risk

Background: Down syndrome (DS) is the most common chromosomal abnormality associated with learning difficulties with reported incidence between1/600 -1/1000 live births. DS (trisomy 21) is the most common chromosomal abnormality seen in clinical practice. Most children with DS have trisomy 21, due to chromosomal non-disjunction during meiosis; however, other abnormalities, such as Robertsonian translocation, mosaic, double or triple aneuploidies have been reported. The association between DS and congenital heart disease (CHD) is well established. Congenital heart disease is the most common cause of death among patients with DS and affected children have an increased risk of mortality.Methods: The present descriptive study was conducted on children who had clinical features suggestive of Down syndrome and who were karyotypically proved as Down syndrome.Results: In 100 cases of down syndrome 60 children were males and 40 children were females. 45 children had congenital heart diseases. The frequency of CHD in down syndrome is 45%. Ventricular septal defect was the most common CHD found 40% children with down syndrome.Conclusions: All children with Down’s syndrome should have a cardiac evaluation at birth. Early referral and screening of all babies born with the clinical phenotype of DS should be encouraged due to the high prevalence of congenital heart defects.

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Down syndrome and congenital heart disease: perioperative planning and management

Journal of Congenital Cardiology ◽

10.1186/s40949-021-00061-3 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Dennis R. Delany ◽

Stephanie S. Gaydos ◽

Deborah A. Romeo ◽

Heather T. Henderson ◽

Kristi L. Fogg ◽

...

Keyword(s):

Congenital Heart Disease ◽

Down Syndrome ◽

Cardiac Surgery ◽

Heart Disease ◽

Congenital Heart ◽

Single Ventricle ◽

Heart Defects ◽

Careful Consideration ◽

Children With Down Syndrome ◽

Perioperative Planning

AbstractApproximately 50% of newborns with Down syndrome have congenital heart disease. Non-cardiac comorbidities may also be present. Many of the principles and strategies of perioperative evaluation and management for patients with congenital heart disease apply to those with Down syndrome. Nevertheless, careful planning for cardiac surgery is required, evaluating for both cardiac and noncardiac disease, with careful consideration of the risk for pulmonary hypertension. In this manuscript, for children with Down syndrome and hemodynamically significant congenital heart disease, we will summarize the epidemiology of heart defects that warrant intervention. We will review perioperative planning for this unique population, including anesthetic considerations, common postoperative issues, nutritional strategies, and discharge planning. Special considerations for single ventricle palliation and heart transplantation evaluation will also be discussed. Overall, the risk of mortality with cardiac surgery in pediatric patients with Down syndrome is no more than the general population, except for those with functional single ventricle heart defects. Underlying comorbidities may contribute to postoperative complications and increased length of stay. A strong understanding of cardiac and non-cardiac considerations in children with Down syndrome will help clinicians optimize perioperative care and long-term outcomes.

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Association Between Down Syndrome and In-Hospital Death Among Children Undergoing Surgery for Congenital Heart Disease

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.113.000764 ◽

2014 ◽

Vol 7 (3) ◽

pp. 445-452 ◽

Cited By ~ 30

Author(s):

Jacqueline M. Evans ◽

Madan Dharmar ◽

Erin Meierhenry ◽

James P. Marcin ◽

Gary W. Raff

Keyword(s):

Congenital Heart Disease ◽

Down Syndrome ◽

Heart Disease ◽

Congenital Heart ◽

Hospital Death

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Congenital heart disease and cardiac procedural outcomes in patients with trisomy 21 and Turner syndrome

Congenital Heart Disease ◽

10.1111/chd.12521 ◽

2017 ◽

Vol 12 (6) ◽

pp. 820-827 ◽

Cited By ~ 12

Author(s):

Raysa Morales-Demori

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Turner Syndrome ◽

Trisomy 21 ◽

Congenital Heart ◽

Procedural Outcomes

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Prevalence and profile of congenital heart disease and pulmonary hypertension in Down syndrome in a pediatric cardiology service

Revista Paulista de Pediatria ◽

10.1590/0103-0582201432218913 ◽

2014 ◽

Vol 32 (2) ◽

pp. 159-163 ◽

Cited By ~ 17

Author(s):

Felipe Alves Mourato ◽

Lúcia Roberta R. Villachan ◽

Sandra da Silva Mattos

Keyword(s):

Congenital Heart Disease ◽

Pulmonary Hypertension ◽

Down Syndrome ◽

Heart Disease ◽

Congenital Heart ◽

Septal Defect ◽

Heart Diseases ◽

Heart Defects ◽

Descriptive Analysis ◽

Atrioventricular Septal Defect

OBJECTIVE:To determine the frequence and profile of congenital heart defects in Down syndrome patients referred to a pediatric cardiologic center, considering the age of referral, gender, type of heart disease diagnosed by transthoracic echocardiography and its association with pulmonary hypertension at the initial diagnosis.METHODS:Cross-sectional study with retrospective data collection of 138 patients with Down syndrome from a total of 17,873 records. Descriptive analysis of the data was performed, using Epi-Info version 7.RESULTS: Among the 138 patients with Down syndrome, females prevailed (56.1%) and 112 (81.2%) were diagnosed with congenital heart disease. The most common lesion was ostium secundum atrial septal defect, present in 51.8%, followed by atrioventricular septal defect, in 46.4%. Ventricular septal defects were present in 27.7%, while tetralogy of Fallot represented 6.3% of the cases. Other cardiac malformations corresponded to 12.5%. Pulmonary hypertension was associated with 37.5% of the heart diseases. Only 35.5% of the patients were referred before six months of age.CONCLUSIONS: The low percentage of referral until six months of age highlights the need for a better tracking of patients with Down syndrome in the context of congenital heart disease, due to the high frequency and progression of pulmonary hypertension.

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