Down syndrome associated malformations

This paper reports the associated malformations and the clinical findings that were observed in 417 cytogenetically confirmed Down Syndrome patients. Among them congenital heart defects have occurred more frequently [75; 17.98%] than osteoarticular malformations [23; 5.52]; eye anomalies [22; 5.27%]; and gastroenterological malformations [n 16; 3.84%]. With regard to prognosis and treatment appropriate counselling has been given to Down Syndrome patients and their families.     

Depression and Down syndrome

Emotional and behavioural disorders are frequent complications of mental retardation that often go unrecognised or untreated. We describe a 13-year old girl with Down's syndrome and depressive illness who responded well to paroxetin. The importance of organizing comprehensive health provision for children with mental retardation in a way that focuses both psychiatric and physical illness is emphasised.     

Prenatal screening for Down syndrome

OBJECTIVE: To investigate the fetal angiotensin II type 1 receptor genotype in pre-eclampsia. DESIGN: Case-control study. POPULATION: Forty-one maternal-fetal pairs from pre-eclamptic pregnancies and 80 maternal-fetal pairs from normotensive pregnancies. METHODS: Maternal and fetal DNA was genotyped at three diallelic polymorphisms, at nucleotides 573, 1062, and 1166, in the coding exon of the angiotensin II type 1 receptor gene, and at a dinucleotide repeat polymorphism in its 3' flanking region. RESULTS: Allele and genotype frequencies at the four polymorphic regions investigated did not differ between pre-eclamptic and normotensive groups, in either fetal or maternal samples. Mothers heterozygous for the dinucleotide repeat allele designated A4 transmitted this allele to the fetus in 15 of 18 informative pre-eclamptic pregnancies and in eight of 26 normotensive pregnancies. This was greater than the expected probability in pre-eclamptic pregnancies (p=0.04) and less than expected in normotensive pregnancies (p<0.005). The 573T variant, which is in partial linkage disequilibrium with the A4 allele, showed a similar distortion of maternal-fetal transmission. CONCLUSION: Angiotensin II type 1 receptor gene expression in the fetus may contribute to the aetiology of pre-eclampsia. It is unclear whether susceptibility is conferred by the fetal genotype acting alone, or by allele sharing by mother and fetus. Possible mechanisms for the effect of the angiotensin II type 1 receptor gene are suggested by the association of the 573T variant with low levels of surface receptor expression on platelets. If receptor expression is similarly genetically determined in the placenta, responsiveness to angiotensin II may be affected, with the potential to influence placentation or placental prostaglandin secretion.     

Hemostatic profile in nephrotic syndrome

OBJECTIVE: To evaluate the coagulation profile and its relation to steroid therapy, and the frequency of thromboembolic complications and its correlation with coagulation parameters in nephrotic syndrome (NS). SETTING: Hospital based. SUBJECTS AND METHODS: Forty children with NS were subdivided into four groups, namely, fresh cases, steroid dependent, remission after therapy and steroid resistant. An equal number of age and sex matched children served as controls. In all the study and control subjects, detailed clinical examination, liver function tests, renal function tests and detailed coagulation profile were done. Evaluation of renal veins and inferior vena cava for the presence of thrombosis was also done by abdominal ultrasonography. RESULTS: Thrombocytosis was detected in 57.5% and the degree of thrombocytosis was directly related to the amount of proteinuria. The mean prothrombin and thrombin times were within normal range in the study children. The activated partial thromboplastine time (APTT) was prolonged in six cases (15%) and three out of these six children had thromboembolic complications. Antithrombin-III level was significantly lower (p < 0.001) whereas protein C and S were significantly elevated (p < 0.001) as compared to controls. The levels became normal with remission of the disease. Steroid therapy significantly increased the levels of proteins C, protein S. AT-III and fibrinogen as compared to controls. Thromboembolic complications were seen in 3 cases (7.6%) and were associated with very low levels of AT-III and protein C and all three had serum albumin below 2 g/dl. CONCLUSIONS: The importance of coagulation profile in nephrotic syndrome is highlighted and a high index of suspicion for thromboembolic complications is warranted in patients with thrombocytosis, hyper fibrinogenemia, prolonged APTT and in children with low levels of AT-III, protein C and protein S.     

Study of Down syndrome in 238,942 consecutive births

Although assistive technology provides a promising means to accommodate for barriers to independence and self-determination for people with mental retardation, such devices are underutilized by this population. The Arc conducted a national survey of the use of assistive technology by people with mental retardation. In four of five areas, the percentage of individuals who used a device was under 10%. In two of these areas, the percentage of individuals who might benefit from a device exceeded the percentage who used a device, and in a third area, the percentage using devices was nearly equal to those who did not use but might benefit from a device. Availability and cost were reported as primary barriers. Suggestions were made to address these issues.     

Down syndrome: 1. Medical aspects

Each organ of a patient with the Down's Syndrome (trisomy 21) shows the pathology. One notices the specific features already with an infant. The life expectation of these children has increased considerably and it depends upon the appearance or not of a heart defect. The ventricular septum defect is most frequent but a small number of these patients show a complex cardiopathy. The incidence of pulmonary hypertension is also high. The obstruction of gastroenteric tract can cause problems from the prenatal phase onwards. The main endocrinological difficulties are dysfunction of the thyroid gland and also infertility. Ocular disorders like refraction disorders occur frequently. Due to decreased conduction, there is a hearing loss. The cellular immunity is clearly reduced, hence, the susceptibility to infections like hepatitis B, increases. The major oral problems are apparently oversized tongue and a high sensitivity to gingivitis.     

Verb use by individuals with Down syndrome

Production of grammatical and lexical verbs in narratives from 29 individuals with Down syndrome and 29 typically developing control subjects matched on linguistic level (Brown's Stages 3, 4, and 5) was examined. We addressed recent theories proposing that verbs are central to syntactic development (Tomasello & Merriman, 1995). Consistent with predictions from the child talk model (Chapman et al., 1992), the individuals with Down syndrome produced fewer lexical or grammatical verbs per utterance compared to the control group but produced a greater diversity of lexical verbs. The findings suggest that the well-documented syntactic deficits evidenced by individuals with Down syndrome may reflect difficulty in accessing verbs when constructing utterances. This difficulty may stem from deficits in auditory short-term memory.     

Early transvaginal measurement of transcerebellar diameter in Down syndrome

OBJECTIVE: To evaluate the screening utility of early transvaginal measurement of the transverse cerebellar diameter for identification of Down syndrome fetuses. METHOD: Measurements of the transverse cerebellar diameter were obtained by transvaginal sonography between 11 and 16 weeks of gestation in 544 fetuses with a normal karyotype and in 37 Down syndrome fetuses. RESULTS: The transverse cerebellar diameter was found to show a fairly constant increment of values throughout the period evaluated with a linear relationship to the gestational age. The measurements obtained in Down syndrome fetuses are within the normal range for gestational age. CONCLUSION: The transverse cerebellar diameter cannot be considered a useful tool in the detection of Down syndrome in early pregnancy.     

Caring for the child with Down syndrome

This article reviews the etiology, treatment, and prognosis of Down syndrome. Effects of Down syndrome on growth and development, specific physiologic manifestations, and implications for school-based practice are discussed.     

Metacarpophalangeal pattern profile analysis in Williams syndrome

Autoantibodies to SSA/Ro and SSB/La antigens may have a pathogenic role in photosensitive skin disease and congenital complete heart block. Since salivary glands are the major target organ in Sjogren's syndrome (SS) we wondered whether these autoantibodies are present in saliva and may be involved in the sicca syndrome. Whole saliva and serum were collected from 15 patients with SS. Elisa analysis disclosed that 8 of the patients had anti-SSA/Ro antibodies, while 6 of them also had anti-SSB/La antibodies. Studies of immunoglobulin classes showed that the sera contained mainly IgG and IgM anti-SSA/Ro or SSB/La antibodies. One serum also contained IgA antibodies. Analysis of the saliva showed that in all positive samples IgG and IgA classes were present, while none of them contained IgM. Elisa and immunoblot analysis of sera and saliva from SLE patients without the sicca syndrome disclosed that both fluids contained anti-Sm antibodies. These findings suggest that the presence of anti-SSA/Ro and anti-SSB/La antibodies in saliva is not a unique phenomenon, characterizing the sicca syndrome. Therefore, their role in the pathogenicity of the Sjogren's syndrome has to be elucidated.     

Maternal serum alpha-fetoprotein and dimeric inhibin A detect aneuploidies other than Down syndrome

OBJECTIVE: Our purpose was to determine whether the combination of maternal serum alpha-fetoprotein, free human chorionic gonadotropin-beta, dimeric inhibin A, and maternal age detects aneuploidies other than Down syndrome. STUDY DESIGN: We retrieved stored serum from pregnancies complicated by aneuploidies other than Down syndrome from 1988 to 1997 (n = 55, mean maternal age 35.2 +/- 5.6 years). Alpha-fetoprotein levels were obtained from our database, and free human chorionic gonadotropin-beta and dimeric inhibin A levels were measured in the thawed serum with use of commercial assays. Analyte values were used in both 3-analyte and 2-analyte multiple-marker screening tests; detection rates were determined at several different Down syndrome risk-positive cutoff values. RESULTS: In the 3-analyte test 58% (32/55) of all aneuploidies were detected with use of both the Down syndrome protocol at a screen-positive risk cutoff value of 1:300 (false-positive rate 17%) and a novel trisomy 18 screening algorithm. However, 67% (37/55) detection was obtained with use of the 2-analyte combination of alpha-fetoprotein and dimeric inhibin A, with both the Down syndrome protocol (screen positive cutoff value 1:300) and the trisomy 18 algorithm: 12 of 13 trisomy 18 (92%), 9 of 17 Turner's syndrome (53%), 10 of 17 other sex chromosome aneuploidies (59%), 1 of 1 trisomy 22 (100%), and 5 of 7 trisomy 13 (71%). CONCLUSIONS: The combination of maternal serum alpha-fetoprotein, dimeric inhibin A, and maternal age detects autosomal trisomies other than Down syndrome at a rate superior to that of the traditional analyte combination.     

Economic evaluation of prenatal screening for Down syndrome in the U.S.A

Maternal serum screening for Down syndrome involves biochemical tests such as alpha-fetoprotein (alpha FP), human chorionic gonadotrophin (hCG) and unconjugated oestriol (uE3), either alone or in combination, that have variable detection and false-positive rates. Choosing a screening protocol requires a trade-off between a desired detection rate and an acceptable false-positive rate. Selecting a screening protocol that maximizes the net benefit to society provides one approach. We have developed a general formula for calculating the per case net social benefit of a screening test and have applied it to United States data. The maximum net benefit associated with each of the various screening options currently available is estimated and the model is further applied to determine the conditions under which the addition of a new marker to an existing protocol can be justified. For each test, or combination of tests, optimal net benefits occur at different detection and false-positive rates. Net benefits are strongly and positively dependent on maternal age; high net benefits are associated with older patients and low, or even negative, net benefits with younger patients. Also, net benefits are affected by the term risk cut-off rate. For triple testing, the 1:351 Down syndrome term risk cut-off appears to provide a higher net benefit than that obtained with 1:250 or 1:300. The optimization of societal net benefit provides a powerful approach to evaluating screening strategies, but the policies used must also consider individuals' freedom in decision making at each step of the prenatal diagnosis pathway.     

Biomarkers of oxidative stress are significantly elevated in Down syndrome

There is convincing epidemiological and in vitro evidence of chronic oxidative stress in individuals with Down syndrome (DS). These individuals develop Alzheimer like changes in the brain in their 30s and 40s. The incidence of autoimmune diseases and cataracts is significantly increased, and the overall ageing process is accelerated. In vitro studies show that impaired viability of DS neurons may be amended by simple chemical antioxidants, such as vitamin E, BHT and propyl gallate, clearly indicative of oxyl radical involvement. However, because of the lack of in vivo experiments, the role of oxidative stress in DS remains controversial. We report here on the results of the chemical analyses of urine samples of 166 individuals, where DS subjects were matched by their siblings. The levels of 8-hydroxy-2'-deoxyguanosine (2.35 +/- 1.69 in DS vs. 1.35 +/- 1.04 in controls, P = 0.00011), a biomarker of oxidative damage to DNA, and malondialdehyde (0.255 +/- 0.158 in DS vs. 0.204 +/- 0.128 in controls, P = 0.033), a biomarker of lipid peroxidation, are significantly elevated in individuals with DS. Dietary influences failed to show any significant correlation with the oxidative stress biomarkers. These results provide direct evidence for increased oxidative stress in individuals with DS.