唐氏综合征合并畸胎瘤一例报告及机制探讨

目的探讨唐氏综合征和畸胎瘤发生可能存在的相关性。方法通过对一例唐氏综合征合并畸胎瘤报告及相关文献复习,概述唐氏综合征可能引起畸胎瘤的原因。结果唐氏综合征患者生殖细胞成熟延迟,癌基因高表达,DNA抗损伤及修复能力下降,促性腺激素水平增高等因素是引起原始生殖细胞突变形成畸胎瘤的原因。结论鉴于唐氏综合征和畸胎瘤以及生殖细胞肿瘤的相关性,临床医生应重视相关检查。     

Evidence that PICALM affects age at onset of Alzheimer's dementia in Down syndrome

It is known that individuals with Down syndrome develop Alzheimer’s disease with an early age at onset, although associated genetic risk factors have not been widely studied. We tested whether genes that increase the risk of late-onset Alzheimer’s disease influence the age at onset in Down syndrome using genome-wide association data for age at onset of dementia in a small sample of individuals (N = 67) with Down syndrome. We tested for association with loci previously associated with Alzheimer’s disease risk and, despite the small size of the study, we detected associations with age at onset of Alzheimer’s disease in Down syndrome with PICALM (β = 3.31, p = 0.011) and the APOE loci (β = 3.58, p = 0.014). As dementia in people with Down syndrome is relatively understudied, we make all of these data publicly available to encourage further analyses of the problem of Alzheimer’s disease in Down syndrome.     

Caries in Portuguese children with Down syndrome

OBJECTIVES:

Oral health in Down syndrome children has some peculiar aspects that must be considered in the follow-up of these patients. This study focuses on characterizing the environmental and host factors associated with dental caries in Portuguese children with and without Down syndrome.

METHODS:

A sibling-matched, population-based, cross-sectional survey was performed.

RESULTS:

Down syndrome children presented a significantly greater percentage of children without caries, 78% vs. 58% of non-Down syndrome siblings. This difference in the DMFT index (number of decayed, missing and filled teeth) essentially reflects data obtained from treated teeth, for which 91% of children with Down syndrome had never had a tooth treated vs. 67% of siblings. This result was statistically significant, whereas results for decayed and lost teeth did not differ between Down syndrome children and their unaffected siblings. Additionally, in Down syndrome children, a delayed eruption of the second molar occurs. Down syndrome children and their siblings have similar oral hygiene habits, but a higher percentage of Down syndrome children visit a dentist before the age of three years, in comparison to their siblings. Bruxism was also more common in Down syndrome children compared to their siblings.

CONCLUSIONS:

Our results show that Portuguese children with Down syndrome have lower caries rates than children without Down syndrome. This reduced prevalence may be associated with the parents'' greater concern about oral health care in Down syndrome children, resulting in their taking them sooner to visit a dentist, as well as to a higher bruxism prevalence and delayed tooth eruption.     

Loss of the extra chromosome 21 in a patient with Down syndrome and myelodysplasia

Monosomy 21 is a rare acquired karyotypic abnormality associated with myeloid disorders. Occurrence of loss of one chromosome 21 in the background of trisomy 21 in Down syndrome, resulting in the pseudo-normalization of trisomy 21, is a novel finding. The case is described of a patient with Down syndrome who acquired such a genetic abnormality as a result of myelodysplastic syndrome.     

Down syndrome associated with systemic lupus erythematosus: a mere coincidence or a significant association?

An 8-year-old male, who had Down syndrome associated with systemic lupus erythematosus (SLE), is described. He also had a partial complement 4 deficiency. This case is a reminder that the physician should be aware of the possibility of an immune defect in a male presenting with SLE at a young age. The question of whether the association of Down syndrome with SLE is coincidental or whether there is a predilection for autoimmune disorders in Down syndome is discussed.     

Neopterin and the risk of dementia in persons with Down syndrome

Persons with Down syndrome show an altered immune response and an increased susceptibility to Alzheimer's disease. In a prospective study, we examined whether the plasma neopterin level, a marker for cell-mediated immune activation and inflammation, is associated with an increased risk of dementia in persons with Down syndrome. Plasma concentrations of neopterin were determined in a population-based study of 394 persons with Down syndrome, who were screened annually for dementia. We used Cox proportional hazards model to determine risk of dementia. Demented persons with Down syndrome have a significantly (p = 0.05) higher plasma neopterin concentration than the non-demented. In the non-demented without autoimmune disorders, in those with a plasma level of neopterin above median, the risk to develop dementia increased to 1.83 (95% confidence interval: 1.04–3.20). High plasma neopterin level is an independent determinant of the risk of dementia in persons with Down syndrome.     

A 2-year-old baby with Downs syndrome, cryptorchidism and testicular tumour

Seminomas are rare germ cell tumours. It occurs usually in men aged over 50 years. Seminomas differ genetically and clinically from germ cell tumours. They have a late age of onset and rarely metastasise. The incidence of testicular carcinoma (seminoma) in patients of Down syndrome has recently been emphasised. One of the predisposing factors for seminoma is undescended testis which not only results in spermatogenic arrest but also in carcinoma in situ. This triad of abnormalities that is cryptorchidism, oligozoospermia and testicular cancer is known as testicular dysgenesis syndrome (TDS). Since there is an increased incidence of tumourogenesis in Down syndrome cases the cryptorchid condition may result in an increased risk for testicular carcinogenesis and its early onset and poor prognosis. Therefore all Down syndrome cases with cryptorchidism should be counselled to go in for surgical descent of testis at the earliest age and also to come for regular follow up for early detection for any foci of malignancy. This is the youngest testicular seminoma ever reported in human. This tumour occurred in a 2-year-old child and it is possible that Trisomy 21 may predispose to early onset of seminoma and such cases should be under regular follow up. Thus improved understanding and identification of various urogenital anomalies associated with Down syndrome will aid in better management of these cases. This case report and review of literature all suggest that Down syndrome is associated with an increased risk of development of seminoma and that too at an early age. This advocates a need for thorough gonadal examination in all cases of Down syndrome.     

Contribution of copy-number variation to Down syndrome–associated atrioventricular septal defects

PurposeThe goal of this study was to identify the contribution of large copy-number variants to Down syndrome–associated atrioventricular septal defects, the risk for which in the trisomic population is 2,000-fold more as compared with that of the general disomic population.MethodsGenome-wide copy-number variant analysis was performed on 452 individuals with Down syndrome (210 cases with complete atrioventricular septal defects; 242 controls with structurally normal hearts) using Affymetrix SNP 6.0 arrays, making this the largest heart study conducted to date on a trisomic background.ResultsLarge, common copy-number variants with substantial effect sizes (OR > 2.0) do not account for the increased risk observed in Down syndrome–associated atrioventricular septal defects. By contrast, cases had a greater burden of large, rare deletions (P < 0.01) and intersected more genes (P < 0.007) as compared with controls. We also observed a suggestive enrichment of deletions intersecting ciliome genes in cases as compared with controls.ConclusionOur data provide strong evidence that large, rare deletions increase the risk of Down syndrome–associated atrioventricular septal defects, whereas large, common copy-number variants do not appear to increase the risk of Down syndrome–associated atrioventricular septal defects. The genetic architecture of atrioventricular septal defects is complex and multifactorial in nature.Genet Med 17 7, 554–560.     

Criticism of the DSM-V risk syndrome: A rebuttal

Short-term memory for verbal and visuospatial information was examined in a group of children and teenagers with Down’s syndrome. Performance on the verbal task was impaired relative to matched control groups, but there were no group differences on the visuospatial task. Relatedly, the Down’s syndrome group showed inferior short-term memory for verbal as opposed to visuospatial information, whereas controls showed the opposite pattern. These findings did not appear to result from a general superiority of nonverbal abilities in the Down’s syndrome group, or from hearing difficulties that might have impacted on the verbal short-term memory task, in which material was presented auditorily. The results are consistent with the suggestion that Down’s syndrome is associated with a selective impairment of the phonological loop component of Baddeley and Hitch’s (1974) working memory model.     

Análisis de la cinematografía del síndrome de Down

IntroductionRare diseases represent a challenge in public health. Down syndrome is one of the most well-known rare diseases, but there are still many aspects of this condition that are unknown. With the aim of using cinema as a tool for education, awareness, and inclusion, an analysis of the representation of Down syndrome in film was carried out from a medical and social perspective.MethodologyThis study conducted a quantitative analysis of the audiovisual material available on Down syndrome in commercial and documentary cinema. Cinematographic aspects, social contexts, and symptoms related to Down syndrome were considered. 14 films were collected from 1992 to 2019.ResultsSeveral high-quality films and documentaries have been produced that show the daily challenges faced by people with Down syndrome. However, these materials are imprecise in terms of medical and genetic aspects. Instead, they focus on the social aspects of the syndrome, such as stigma, romantic and sexual relationships, parenting difficulties for parents, and the abilities and skills of people with Down syndrome.ConclusionAlthough cinema can be a useful tool to understand relevant aspects of Down syndrome, little accurate information about the medical, genetic and pharmacological aspects of the disease was found in the analyzed films. However, these films allow for learning about the social and behavioral aspects of the syndrome, which is of great value in helping to break down stereotypes and stigma associated with this disease.     

Hematopoietic disorders in Down syndrome

Patients with Down syndrome have an increased risk of developing various hematological disorders. In this article, the clinical characteristics and differential diagnosis of the hematological disorders associated with Down syndrome are reviewed, and the underlying molecular mechanisms discussed.     

Down syndrome associated with father's age in Norway.

Records of births in Norway in 1967 to 1978 were examined for evidence of an increased risk of Down syndrome associated with older paternal age. From among some 685 000 total births with known maternal and paternal age, 693 cases of Down syndrome were reported to the Medical Birth Registry of Norway. The effect of paternal age was assessed by classifying fathers as young and old on the basis of several definitions. The effect of maternal age was removed by stratifying the data on single years of mothers' age. When fathers were considered young if they were less than or equal to 49 and old if they were less than or equal to 50, the analysis yielded a statistic for the test of a one-sided hypothesis which was significant at the 0.05 level. There appears to be an increase risk (perhaps 20 to 30%) of Down syndrome associated with older fathers, independent of maternal age effect. If this increase does in fact exist, it is much smaller than the increases in risk associated with advancing maternal age, and because older men contribute a relatively small proportion of total births their contribution to the communal burden of Down syndrome is quite small. However, the finding is of aetiological interest and is the first indication of a significant paternal age effect where control for maternal age has been stringent.     

Functional genomics of the Down syndrome

Down syndrome, as a phenotypic result of trisomy 21, is a complex condition with a set of over 30 phenotypic features, which manifest themselves with varying frequencies among affected individuals. The importance for molecular medicine of understanding the molecular mechanisms underlying Down syndrome becomes fully appreciated when a striking feature of Down syndrome is taken into account: that the overdose of otherwise perfectly normal genes causes disorders of human health, indistinguishable from major public health problems of the general population, such as mandatory early onset Alzheimer s degeneration, increased risk of leukemia, and protection from cancer of solid tissues. The DNA sequence of human chromosome 21 is, at the moment, the most complete piece of DNA sequence known in the whole of human genome. The challenge for the future is an integrated, multidisciplinary approach to the molecular biology of chromosome 21 genes, in conjunction with the research into the variation in their genotype, expression, and function in the normal population, in Down syndrome individuals with well-characterized phenotypic traits, and in euploid patients suffering from diseases associated with phenotypic components of Down syndrome: mental retardation, developmental defects, hematological and solid tissue malignancies, and Alzheimer s disease.     

Apo E genotypes and risk of dementia in Down syndrome

The relationship between apo E genotypes and risk of dementia in Down syndrome is not clear. Accordingly, we have analysed this locus in 20 demented and 25 nondemented individuals with Down syndrome and combined these data with other studies in a meta-analysis. The meta-analysis revealed an estimated odds ratio for dementia of 2.74 (95% CI 1.34–5.58) (P = .0004) for apo ϵ4 carriers compared with apo ϵ3/ϵ3, similar to that observed in late-onset Alzheimer's disease. An additional parallel with late-onset Alzheimer's disease was shown by the apo ϵ2 allele, which was associated with decreased dementia risk in Down syndrome (odds ratio for apo ϵ2/ϵ2 + ϵ2/ϵ3 = 0.37 (95% CI 0.14–0.96)). Thus, apo E genotypes are associated with similar risk effects in Down syndrome dementia and late-onset Alzheimer's disease. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:344–347, 1999. © 1999 Wiley-Liss, Inc.     

Call for change in prenatal counseling for Down syndrome

The American Journal of Medical Genetics Part A is to be congratulated for taking a leadership role by publishing a number of papers challenging the status quo of prenatal counseling for Down syndrome and of care for children and adults with Down syndrome. Parents want to know about the future abilities and potential of their fetus with Down syndrome, not simply negative medical information that may be outdated. Those providing counseling and those providing medical care could benefit from contact with individuals with Down syndrome outside the medical context. It is imperative that each person with Down syndrome be viewed as a unique individual with particular talents. Medical care providers should work with parents to help the child or adult with Down syndrome reach his/her goals.     

Autosomal trisomy and maternal use of multivitamin supplements

Recent reports suggest that women carrying certain polymorphisms of folate genes associated with suboptimal folate status might be at increased risk for having a child with Down syndrome or other autosomal trisomies, and hypothesized that maternal use of multivitamin supplements might reduce such risk. To evaluate this hypothesis, we examined data from a population-based case-control study, and contrasted cases of Down syndrome, trisomy 18, and trisomy 13, with unaffected controls. Periconceptional multivitamin use, compared to no such use, was associated with an odds ratio (OR) of 0.9 (95% confidence interval [CI], 0.6-1.3) for having a pregnancy affected by an autosomal trisomy. The OR was 0.8 (95% CI, 0.5-1.3) for Down syndrome and 1.4 (95% CI, 0.5-3.6) for trisomies 13 and 18, with little variation by maternal race or age. Periconceptional multivitamin use was not associated with a major reduction in the risk for common autosomal trisomies.     

C677T mutation in the 5,10-MTHFR gene and risk of Down syndrome in Italy

The C677T polymorphism of the MTHFR gene has been associated to maternal risk of Down syndrome, due to the detection of an higher prevalence of the T allele among mothers of children with trisomy 21, compared to control mothers. In order to confirm this association, we studied the presence of the C677T in 64 mothers of Down syndrome children and 112 controls from central Italy. An higher incidence of the mutant T allele in controls (48.2%) than in Down syndrome children mothers (44%) was detected. These results do not support the presence of an increased risk of Down syndrome in mothers carriers of the T allele in the Italian population.