Down Syndrome (Down's Syndrome)

A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe MENTAL RETARDATION. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)

Also Known As:

Networked: 6126 relevant articles (139 outcomes, 697 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Trisomy (Trisomies)
2.	Alzheimer Disease (Alzheimer's Disease)
3.	Dementia (Dementias)
4.	Chromosome Aberrations (Chromosome Abnormalities)
5.	Heart Diseases (Heart Disease)

Experts

1.	Nicolaides, K H: 58 articles (03/2015 - 04/2000)
2.	Lubec, G: 53 articles (01/2007 - 09/2000)
3.	Spencer, K: 44 articles (09/2015 - 02/2000)
4.	Nicolaides, Kypros H: 39 articles (01/2014 - 03/2003)
5.	Spencer, Kevin: 26 articles (01/2014 - 10/2002)
6.	Fountoulakis, M: 26 articles (01/2007 - 01/2001)
7.	Kagan, K O: 24 articles (07/2015 - 09/2007)
8.	Cairns, N: 24 articles (11/2006 - 09/2000)
9.	Wright, D: 20 articles (01/2015 - 04/2008)
10.	Palomaki, Glenn E: 19 articles (11/2015 - 02/2003)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Down Syndrome:

1.	alpha-Fetoproteins (AFP)IBA 08/01/2002 - "Integration of NT and second trimester serum AFP and hCG assay yielded the best screening efficacy for Down syndrome." 03/01/1999 - "A policy of first trimester scanning followed by serum alpha-fetoprotein screening and additional scanning as clinically indicated is effective in detecting major structural abnormalities, but scanning at 18-22 weeks and serum biochemical screening for trisomy 21 improved the detection rates. " 08/01/1994 - "These results support the mathematical model that hCG is the major contributor to the increased sensitivity of multi-analyte screening and demonstrate that screening programs can attain substantial improvement in detection of second-trimester Down syndrome by adding hCG to AFP and age." 12/01/1995 - "AFP, hCG, uE3] has been found effective in identifying the majority of pregnancies with Down syndrome in the second trimester. " 09/01/2011 - "Decreased AFP concentrations increase the calculated risk of Down's syndrome; therefore falsely low AFP, due to assay interference, may artificially increase a patient's risk, and have the potential to cause false screen positive results. "
2.	Chorionic Gonadotropin (Human Chorionic Gonadotropin)FDA LinkGeneric 02/01/1994 - "The median maternal serum free beta human chorionic gonadotropin (hCG) multiple of the median (MOM) of 480 Down syndrome cases in the second trimester was 2.64, significantly greater than the reported median MOM of intact hCG (p < 0.0001). " 03/01/2007 - "The results of our analysis suggest that in a first-trimester Down syndrome screening protocol free beta-human chorionic gonadotropin achieves higher sensitivity and lower false-positive results than intact human chorionic gonadotropin . " 09/01/2007 - "The purpose of this study was to compare the effectiveness between total human chorionic gonadotropin (hCG) and free beta-hCG in two-marker Down syndrome screening programs during the second trimester in a Taiwanese population. " 03/01/2007 - "Meta-analysis of first trimester Down syndrome screening studies: free beta-human chorionic gonadotropin significantly outperforms intact human chorionic gonadotropin in a multimarker protocol." 03/01/1998 - "Published studies have reached varying conclusions as to the benefit of replacing human chorionic gonadotropin (hCG) measurements with the free beta-subunit of hCG (the free beta-subunit) for Down syndrome screening. "
3.	Biological Markers (Surrogate Marker)IBA 06/01/2006 - "In prenatal screening for Down syndrome, serum marker values can be adjusted using values from a previous pregnancy to avoid the problem of women having a high chance of recurrent false-positive results. " 09/06/2011 - "Prenatal screening test for Down syndrome (DS) can be improved by discovery of novel biomarkers. " 05/01/2013 - "The objective of the study was to evaluate the efficacy of maternal serum markers in detecting Down syndrome after 18 weeks of gestation in women who book late for maternity care in a large national retrospective study. " 04/01/2008 - "First-trimester maternal serum screening for Down syndrome (DS) can be improved by the use of additional serum markers. " 10/01/2004 - "A number of serum markers have been proposed to improve the sensitivity (and specificity) of the triple test, which, until now, has been the gold standard in second-trimester serum screening for Down's syndrome. "
4.	Pregnancy-Associated Plasma Protein-A (PAPP-A)IBA 01/01/2006 - "First trimester screening using maternal age, NT, free beta-hCG and PAPP-A is highly effective for the detection of trisomy 21 and is associated with a sensitivity of about 90% for 5% false-positive patients." 06/01/2009 - "Pregnancies conceived using assisted reproductive technologies (ART) have low levels of pregnancy-associated plasma protein-A (PAPP-A) leading to a high rate of false-positive results in first trimester screening for Down syndrome." 06/01/1998 - "This study evaluates diagnostic efficacy of PAPP-A and F beta-hCG in the detection of first trimester pregnancy abnormalities, including Down syndrome (DS). " 04/01/2014 - "in our study population the detection rate for trisomy 21, using the combined risk calculation based on maternal age, fetal NT, maternal PAPP-A and free β-hCG levels, was superior to the application of either parameter alone. " 01/01/2014 - "Previous studies showed that soluble LHCGR/hCG-sLHCGR concentrations in serum or plasma combined with PAPP-A and free βhCG significantly increased the sensitivity of Down's syndrome screen at early pregnancy without altering the false positive rate. "
5.	DNA (Deoxyribonucleic Acid)IBA 01/01/2005 - "This improved methodology is proposed for longitudinal in vivo studies and in the present work its application made it possible to assess a significant increase of DNA in pediatric Down Syndrome patients compared to healthy controls of the same age." 06/01/2012 - "Currently, two applications for NIPD of Down syndrome have been developed with potential and have displayed positive results; the NIPD using next-generation sequencing technologies and the NIPD using the methylated DNA immunoprecipitation (MeDIP) real-time quantitative polymerase chain reaction (qPCR). " 07/04/1998 - "The PCR-based DNA diagnostic test has great potential for improved prenatal diagnosis of Down's syndrome, with the advantage that results may be available within a day." 01/01/2015 - "The study aimed to validate the efficacy of detection of fetal cell-free DNA in maternal plasma of trisomy 21, 18 and 13 in a clinical setting. " 04/15/2015 - "The study demonstrated that ERG gene is hypermethylated in cff DNA but hypomethylated in maternal DNA; and the median concentration of ERG gene in the trisomy 21 case group is higher than that in the gestational trimester matched normal group. "
6.	donepezil (Aricept)FDA LinkGeneric 07/01/2007 - "Preliminary study of the safety and efficacy of donepezil hydrochloride in children with Down syndrome: a clinical report series." 03/01/2005 - "Dramatic improvement in Down syndrome-associated cognitive impairment with donepezil." 01/01/2011 - "Donepezil significantly improves abilities in daily lives of female Down syndrome patients with severe cognitive impairment: a 24-week randomized, double-blind, placebo-controlled trial." 01/15/2003 - "Donepezil for the treatment of language deficits in adults with Down syndrome: a preliminary 24-week open trial." 12/01/2010 - "The objective of this 10-week, randomized, double-blind, placebo-controlled multicenter study was to assess the efficacy and safety of donepezil for the treatment of cognitive dysfunction exhibited by children with Down syndrome (DS). "
7.	bosentan (Tracleer)FDA Link 04/15/2013 - "After 12 months of bosentan therapy, both with and without Down's syndrome patients showed an improvement in WHO functional class (Down: 2.5 ± 0.5 vs 2.9 ± 0.6, p=0.005; controls: 2.5 ± 0.5 vs 2.9 ± 0.5, p=0.000002), 6-minute walk distance (Down: 288 ± 71 vs 239 ± 74 m, p=0.0007; controls: 389 ± 80 vs 343 ± 86 m, p=0.00003), and hemodynamics (pulmonary flow, Down: 4.0 ± 1.6 vs 3.5 ± 1.4 l/m/m(2), p=0.006; controls: 3.5 ± 1.4 vs 2.8 ± 1.0 l/m/m(2), p=0.0005; pulmonary to systemic flow ratio, Down: 1.4 ± 0.7 vs 1.0 ± 0.4, p=0.003; controls: 1.1 ± 0.7 vs 0.9 ± 0.3, p=0.012; pulmonary vascular resistance index, Down: 15 ± 9 vs 20 ± 13 WUm(2), p=0.007; controls: 2 0 ± 10 vs 26 ± 15 WUm(2), p=0.002). " 05/01/2009 - "In conclusion, findings suggested that in patients without Down's syndrome, longer term bosentan treatment resulted in a persistent improvement in QoL and stabilization of exercise capacity." 04/15/2013 - "Aim of the study was to evaluate the long-term effects of bosentan in adult patients with CHD-related PAH with and without Down's syndrome. " 03/20/2013 - "In this study we evaluated 4 years treatment effect of bosentan on exercise capacity and quality of life and survival rates in 64 adult patients with PAH associated with CHD, including patients with Down syndrome (DS). " 01/01/2013 - "In this observational study adults with Down's syndrome with a confirmed diagnosis of ES (World Health Organization functional class III) and receiving bosentan therapy and were followed up long term. "
8.	inhibin AIBA 11/01/2006 - "Seventy-nine matched case-control sets of maternal serum samples (each Down syndrome case matched to 5 controls) from 11 through 13 completed weeks of gestation were taken from the sample bank of the First and Second Trimester Evaluation of Risk Consortium, a population-based study, and assayed for levels of free beta-hCG, total hCG, and inhibin A. " 04/01/2004 - "Several studies report the role of dimeric inhibin-A in assessing risk for fetal Down syndrome. " 06/01/2000 - "Native Japanese dimeric inhibin A median values in this study are 1.77 times higher in Down's syndrome cases than in unaffected pregnancies. " 03/01/1998 - "The aim of this study was to evaluate the additional value of dimeric inhibin-A serum concentration in second trimester multiple-marker screening tests for pregnancies affected by Down's syndrome. " 04/01/2014 - "Effect of smoking status on inhibin-A in second-trimester prenatal screening for Down syndrome."
9.	dichlorobis(azomycin)platinum IIIBA 04/01/2014 - "Prenatal testing for Down syndrome through the use of non-invasive prenatal testing (NIPT) has been increasingly implemented in clinical practice and a recent cost analysis suggests that NIPT is cost effective when compared to other screening modalities in high risk populations. " 03/24/2015 - "NIPT may be used to reduce unnecessary invasive prenatal diagnosis by improving the efficacy of current mid-trimester screening strategy, particularly for trisomy 21." 10/01/2015 - "A cross-sectional questionnaire study across nine maternity units and three conferences in the UK designed to assess opinions regarding test delivery and how information should be communicated to women when offered Down's syndrome screening (DSS) or diagnosis using invasive (IDT) or non-invasive testing (NIPT). " 06/01/2015 - "The aim of the study is to study pregnant women's views on noninvasive prenatal testing (NIPT) for Down syndrome and the potential to test for a broader range of conditions. " 01/01/2015 - "The aims of this study were to test the utility of benchtop NGS platforms for NIPT for trisomy 21 using previously published z score calculation methods and to optimize the sample preparation and data analysis with use of in silico and physical size selection methods. "
10.	HormonesIBA 04/10/1991 - "Pregnancy hormone levels signal trisomy 21, improved screening, lower costs possible." 01/01/1991 - "Lack of efficacy of short term thyroid hormone therapy in Down syndrome." 05/01/1989 - "Short-term efficacy of thyroid hormone supplementation for patients with Down syndrome and low-borderline thyroid function." 09/01/2012 - "Resistance to thyroid hormone and Down syndrome: coincidental association or genetic linkage?" 10/01/2011 - "To investigate whether having a Down syndrome pregnancy at a relatively young age is associated with lower ovarian reserve as reflected by lower antimüllerian hormone (AMH) levels and the occurrence of earlier menopause. "

Therapies and Procedures

1.	Drug Therapy (Chemotherapy) 01/01/2003 - "Despite these improvements in chemotherapy, allogeneic BMT from a matched family donor remains the best option for most patients (excluding Down syndrome, APL, and possibly those with inv16). " 07/01/1999 - "Neonates with Down's syndrome and abnormal myelopoesis may achieve spontaneous remission, and older children with Down's syndrome and AML can be treated successfully with intensive chemotherapy, without BMT." 01/01/2013 - "Down syndrome: genes, model systems, and progress towards pharmacotherapies and clinical trials for cognitive deficits." 02/01/2014 - "Most of the pharmacotherapies designed to improve cognitive performance in Down's syndrome have been attempted in Down's syndrome mouse models during adult life stages. " 02/01/2014 - "Prenatal pharmacotherapy rescues brain development in a Down's syndrome mouse model."
2.	Bone Marrow Transplantation (Transplantation, Bone Marrow) 02/01/2009 - "We report a sixteen-year-old boy with Down syndrome and relapse of AML (M7), who has been in complete remission (CR) more than 12 months after bone marrow transplantation (BMT) from an HLA-matched sibling donor. " 11/01/1993 - "The factors associated with an increased risk of remission death were: young age, a higher leucocyte count, bone marrow transplantation, and Down's syndrome. " 11/15/2008 - "Finally, we report a novel constitutively active MPL mutant, MPLT487A, observed in a non-Down syndrome childhood AMKL that induces a myeloproliferative disease in mouse bone marrow transplantation assay." 03/01/1999 - "The authors discuss a two-year-old male with Down syndrome who presented 2 months after allogeneic bone marrow transplantation with severe oculogyric crisis, without other complaints. " 09/01/1996 - "We report 18 patients with Down's syndrome who underwent bone marrow transplantation, and review nine previously published patients. "
3.	Therapeutics 10/01/2014 - "Recent advancements in molecular genetics raise the possibility that therapeutics or a 'cure' for Down syndrome (DS) may become available. " 01/01/2012 - "Molecular and cellular alterations in Down syndrome: toward the identification of targets for therapeutics." 09/01/2011 - "Remarkable advances have been made in recent years towards therapeutics for cognitive impairment in individuals with Down syndrome (DS) by using mouse models. " 05/01/2011 - "In combination with the national annual data of the Working Group for Prenatal Diagnostics and Therapeutics on numbers of Down syndrome pregnancies not aborted after diagnosis, national figures on birth prevalence were constructed. " 01/01/2010 - "In the long term, Tc1 mice will contribute to the development and the screening of new therapeutics, with the goal of improving all the impairments reported in Down syndrome."
4.	Adenoidectomy 01/01/2004 - "The results of the study suggest that the efficacy of adenoidectomy in children with Down syndrome is significantly less than that in controls and should influence surgical decision making in these children." 01/01/2004 - "To compare the efficacy of adenoidectomy in children with Down syndrome and control patients. " 01/01/2004 - "Efficacy of adenoidectomy in the treatment of nasal and middle ear symptoms in children with Down syndrome." 01/01/2014 - "We do not understand why adenoidectomy works in different subgroups at different ages, nor its effects in special populations, such as children with Down syndrome. " 01/01/2004 - "Patients with Down syndrome were 7.7 times (95% confidence interval, 2.3-25.3) more likely to have chronic ear drainage after adenoidectomy. "
5.	Middle Ear Ventilation (Tympanostomy) 08/05/1999 - "The present study was carried out to determine the efficacy of tympanostomy tube insertion in children with Down syndrome. " 08/05/1999 - "The efficacy of the tympanostomy tube insertion for children with Down syndrome was much lower than in control children. " 08/05/1999 - "Moreover, improvement in hearing acuity after the placement of tympanostomy tubes was not always achieved in children with Down syndrome. " 07/01/2015 - "Increased pediatric age, longer-acting tympanostomy tubes, and history of trisomy 21 may negatively influence likelihood of closure." 07/01/2014 - "Frequent draining ear and extremely immature mastoid pneumatization, regardless of the presence or absence of a past history of tympanostomy tube insertion, were clinically important characteristics of COM in patients with Down syndrome."