Achalasia and Down syndrome: a unique association not to be missed

Achalasia is a rare primary oesophageal motility disorder that presents as a functional obstruction at the oesophago-gastric junction. The prevalence of achalasia in Down syndrome is much higher, which implies a unique association between these two uncommon conditions. Although the exact aetiology of achalasia is unknown, studies have proposed that its pathogenesis is related to autoimmune, infectious or genetic factors, leading to the intrinsic loss of inhibitory myenteric neurons in both the oesophagus and lower oesophageal sphincter. We herein report the case of a 16-month-old girl with Down syndrome and achalasia who was initially treated for gastro-oesophageal reflux disease. The diagnosis of achalasia was made only when her condition deteriorated, with subsequent failure to thrive, and upon further investigations, including barium swallow study and upper endoscopy. We also review the various mechanisms postulated in the development of achalasia in Down syndrome, as well as the various treatment modalities available for this rare disorder.     

Thyroid dysfunction in Down syndrome

Background: Down syndrome is associated with various forms of thyroid dysfunction, hypothyroidism being the most common. The additive effects of both co-morbid conditions lead to further amplification of the clinical problems in these children with Down syndrome. Objective: The purpose of this prospective study was to know the prevalence of thyroid dysfunction in Down Syndrome children below the age of 14 years and to correlate the features of Down Syndrome with those of thyroid dysfunction. Methods: In all 32 Down syndrome children were grouped as euthyroid, compensated and uncompensated hypothyroidism on the basis of their T3, T4 and TSH levels and the features of were compared using the student's t-test. Results: Hypothyroidism was seen in 5 out of 32 cases (15.6%) of which 1 (3.1%) had uncompensated while the other 4 (12.5%) had a compensated hypothyroidism. Hyperthyroidism was not observed in any of the cases. The prevalence of hypothyroidism of 16.7% on the age group 0 -1 year could well be a reflection of congenital hypothyroidism while 20% prevalence in the age group 9 - 12 could imply acquired hypothyroidism. The mean values of the developmental quotient (D.Q.) and the Rao's index in Down syndrome cases with hypothyroidism was 49 5.1 and 0.15 0.06 respectively while that of euthyroid Down syndrome patients were 52 5.54 and 0.17 0.04 respectively ('p' value > 0.05), the differences though obvious yet not statistically significant. Conclusion: It thus seems necessary to screen all Down syndrome children for thyroid dysfunction. Key words: Down syndrome, hypothyroidism.     

Hypothyroidism presenting as cardiac tamponade in Down syndrome

Down syndrome is the commonest chromosomal anomaly. It is often associated with hypothyroidism, which may rarely present with cardiac tamponade as the earliest manifestation and prompt treatment with L-thyroxine is life saving. A six-month-old female child diagnosed as a case of Down syndrome presented with shortness of breathing for last 1 1/2 months. Facial dysmorphism, characteristic of Down syndrome was present. Echocardiography revealed large pericardial effusion and right ventricular diagnostic collapse. A case of Down syndrome with hypothyroidism and cardiac tamponade was kept in mind. She was treated with L-thyroxine and clinical status improved.     

Second-trimester ultrasound to detect fetuses with Down syndrome: a meta-analysis

CONTEXT: Second-trimester prenatal ultrasound is widely used in an attempt to detect Down syndrome in fetuses, but the accuracy of this method is unknown. OBJECTIVE: To determine the accuracy of second-trimester ultrasound in detecting Down syndrome in fetuses. DATA SOURCES: English-language articles published between 1980 and February 1999 identified through MEDLINE and manual searches. STUDY SELECTION: Studies were included if they recorded second-trimester findings of ultrasonographic markers, chromosomal abnormalities, and clinical outcomes for a well-described sample of women. A total of 56 articles describing 1930 fetuses with Down syndrome and 130 365 unaffected fetuses were included. DATA EXTRACTION: Articles were independently reviewed, selected, and abstracted by 2 reviewers. Discrepancies in data abstraction were resolved by consensus with a third reviewer. Overall estimates of sensitivity, specificity, and positive and negative likelihood ratios were calculated for the following markers: choroid plexus cyst, thickened nuchal fold, echogenic intracardiac focus, echogenic bowel, renal pyelectasis, and humeral and femoral shortening. Results were stratified by whether markers were identified in isolation or in conjunction with fetal structural malformations. DATA SYNTHESIS: When ultrasonographic markers were observed without associated fetal structural malformations, sensitivity for each was low (range, 1%-16%), and most fetuses with such markers had normal outcomes. A thickened nuchal fold was the most accurate marker for discriminating between unaffected and affected fetuses and was associated with an approximately 17-fold increased risk of Down syndrome. If a thickened nuchal fold is used to screen for Down syndrome, 15 893 average-risk women or 6818 high-risk women would need to be screened for each case of Down syndrome identified. For each of the other 6 markers, when observed without associated structural malformations, the marker had marginal impact on the risk of Down syndrome. Because the markers were detected in only a small number of affected fetuses, the likelihood of Down syndrome did not decrease substantially after normal examination findings (none of the negative likelihood ratios were significant). CONCLUSIONS: A thickened nuchal fold in the second trimester may be useful in distinguishing unaffected fetuses from those with Down syndrome, but the overall sensitivity of this finding is too low for it to be a practical screening test for Down syndrome. When observed without associated structural malformations, the remaining ultrasonographic markers could not discriminate well between unaffected fetuses and those with Down syndrome. Using these markers as a basis for deciding to offer amniocentesis will result in more fetal losses than cases of Down syndrome detected, and will lead to a decrease in the prenatal detection of fetuses with Down syndrome.     

'Moya' than meets the eye: neurofibromatosis type 1 associated with Moyamoya syndrome

Moyamoya syndrome (MMS) is an uncommon association of neurofibromatosis type 1 (NF1). We describe a seven-year-old chinese girl with NF1 and unilateral MMS with multiple hyperintensities on T2-weighted magnetic resonance (MR) images. The ischaemic lesions in the ipsilateral white matter were hypointense on fluid attenuated inversion recovery (FLAIR) MR images, in contrast to the hyperintense "unidentified bright objects" (UBOs) of NF1. Neuroradiologists should be aware of associated MMS in NF1 patients, and distinguish the effects of ischaemia from UBOs, especially on FLAIR MR imaging.     

Accuracy of the clinical diagnosis of Down syndrome

OBJECTIVES: To determine the accuracy of clinical diagnosis of Down syndrome, identify problems in reaching a diagnosis, to provide recommendations for improvement and estimate a minimum prevalence for all types of Down syndrome. DESIGN: A retrospective observational study was carried out over a five-year period. Genesis, a database located in the Department of Medical genetics, was used to identify the number of Down syndrome karyotypes including trisomy, translocation, and mosaic sample variants. Age of diagnosis was determined using date of receipt. Karyotyping requests for a clinical diagnosis of Down syndrome were also identified. Patient notes and cytogenetic laboratory reports were used to identify clinical indication for karyotyping. SETTING: Regional Genetics Centre, covering all cytogenetic analyses for referrals within the entire Northern Ireland population. RESULTS: 208 postnatal cases of Down syndrome were identified, 197 (94.7%) trisomy, 3 (1.45%) translocation, and 8 (3.85%) mosaic variants. 112 (54.8%) were male and 96 (46.2%) female. 268 samples were taken to confirm or exclude a clinical diagnosis of Down syndrome. 185 of these had Down syndrome, 77 were normal, and 6 had another abnormality. 90% and 100% of trisomy and translocation Down syndrome respectively were diagnosed on the basis of clinical features. This fell to 37.5% of mosaic Down syndrome patients being diagnosed clinically (p < 0.001). Simian crease, sandal gap, epicanthic folds, hypotonia, upslanting palpebral fissures, and protruding tongue are the most frequent characteristic features seen. Similarly epicanthic folds, protruding tongue, simian crease and sandal gap, hypotonia, and upslanting palpebral fissures are also described in a significant proportion of karyotypically normal individuals, thus arousing a suspicion of Down syndrome. 89.4% of patients were diagnosed between day 1 and 7 of life. Of 10.6% patients diagnosed after day 7 of life, 7.6% were adults and 3% children. The minimum prevalence was estimated at 167.9 per 100,000, or 1 in 595 births. CONCLUSION: In a defined population, with a prevalence of around 1 in 600 births, accurate clinical diagnosis occurred in 90%, 100%, and 37.5% of trisomy, translocation, and mosaic patients. 49.5% of patients had one or more of the following phenotypic findings: Simian crease, sandal gap, epicanthic folds, hypotonia, upslanting palpebral fissures, and protruding tongue. However, the same six features aroused a suspicion of Down syndrome in individuals with normal karyotyping, thus causing undue stress and worry to parents. Mosaic cases may be more common than previously recognised, and often do not have dysmorphic features. It is therefore a diagnosis that should always be considered in those who are educationally subnormal without a definitive diagnosis.     

Moyamoya病CT、MRI和DSA的诊断价值比较

目的:比较CT、磁共振成像(MRI)和数字减影血管造影(DSA)对Moyamoya病的诊断价值.方法:对经临床和影像学证实的153例Moyamoya患者的CT、MRI及DSA进行回顾性分析.153例患者中,83例有CT平扫,30例有CT增强,25例有CT血管造影(CTA);135例有MRI SE序列平扫,3D-TOF MR血管成像(MRA)130例;113例有DSA.结果:83例CT平扫发现脑梗死38例,脑出血33例,仅3例隐约可见丘脑、基底节区和鞍上池的略高密度烟雾血管影;135例MRI平扫患者中发现脑梗死108例,脑出血38例.CT平扫、CTA、CT增强诊断阳性率分别为3.6%(3/83)、92%(23/25)和93.3%(28/30).MRI平扫和3D-TOF MRA的诊断阳性率分别为95.6%(129/135)和100%(135/135).DSA诊断阳性率100%(113/113).CTA、MRA和DSA显示颈外动脉侧支循环的阳性率分别为24%(6/25)、27.7%(36/130)和35.4%(40/113).与DSA比较,CTA和MRA显示烟雾血管少,常高估脑动脉狭窄.结论:DSA是诊断烟雾病的最佳影像学手段,但具有创伤性.CT增强、CTA、MRI平扫和MRA均是诊断烟雾病的重要方法,CT平扫难以诊断烟雾病.     

应用短串联重复序列诊断唐氏综合征

目的:探讨联合应用6个短串联重复序列(STR)为标记,结合聚合酶链反应(PCR),单链构象多态性分析(SS-CP)诊断唐氏综合征的可行性。方法:选择21号染色体上的D21S1414、D21S1413、D21S1432、D21S1437、D21S1446、D21S2054,6个高杂合度的STR基因座扩增,对扩增产物用变性聚丙烯酰胺凝胶电泳,银染技术分析,通过观察DNA电泳的带型特征诊断唐氏综合征。结果:82例患儿经STR-PCR分析确认31例为唐氏综合征。结论:该方法可以直观、简便、快速地诊断唐氏综合征,为基因诊断唐氏综合征提供实验依据,有利于对唐氏综合征大规模产前诊断的开展。     

Thyroid dysfunction in children with Down syndrome: a literature review

Introduction

This article is an evidence-based review of thyroid disease in children with Down syndrome, including a comparison between various professional guidelines for the management of thyroid disease in children with Down syndrome. Aspects of thyroid disease which are discussed include: congenital hypothyroidism; autoimmune thyroid disease; subclinical hypothyroidism; and hyperthyroidism. The national professional guidelines of Ireland, the United Kingdom, the United States of America, Australia and Canada are reviewed and compared.

Materials and methods

A literature search was conducted using Medline and PubMed. Search terms included ‘Down syndrome’ and ‘thyroid disease’, ‘hypothyroidism’, ‘hyperthyroidism’, ‘subclinical hypothyroidism’.

Results

Eighty-nine articles were retrieved and reviewed for inclusion. The guidelines on the medical management of children with Down syndrome of five expert groups have also been retrieved and reviewed for this discussion. These various guidelines offer largely similar advice regarding frequency of thyroid function tests, with only Ireland and the UK testing less frequently than annually. Only the United Kingdom and Irish Down Syndrome Medical Interest Group guidelines suggest testing for thyroid antibodies at every thyroid screen. None of the guidelines offer suggestions on the optimal course of action to pursue after the discovery of subclinical hypothyroidism.

Conclusion

In conclusion, more evidence is required regarding the optimal course of treatment for subclinical hypothyroidism. Such evidence may be best obtained by conducting a prospective randomized control trial.     

8例小儿烟雾病的临床和X线影象分析

本文报告了8例小儿烟雾病。并均经脑血管造影所证实。作者就小儿烟雾病的临床和X线影象特点进行了讨论。指出,小儿烟雾病的临床表现多以脑缺血症状为主。在小儿,头部CT扫描见到多发性脑梗塞和原发性脑室出血者,应高度怀疑本病。     

Croatian population data for arylsulfatase a pseudodeficiency-associated mutations in healthy subjects,and in patients with Alzheimer-type dementia and Down syndrome

BACKGROUND: Arylsulfatase A (ASA) is a lysosomal enzyme involved in catabolism of cerebroside sulfate, whose deficiency causes metachromatic leukodystrophy, a rare autosomal recessive disorder characterized by storage of cerebroside sulfate, mainly in the nervous system. Low ASA activities have also been reported in healthy individuals and several neuropsychiatric disorders due to the condition termed ASA pseudodeficiency. The aim of this study was to establish frequency of two mutations associated with ASA pseudodeficiency in healthy individuals in the Croatian population as well as in persons with Alzheimer-type dementia and Down syndrome. METHODS: Presence of N350S and 1524+95 A-->G pseudodeficiency mutations was detected in genomic DNA extracted from leukocytes of healthy subjects (n = 125) and of patients with Alzheimer-type dementia (n = 18) and Down syndrome (n = 21). Arylsulfatase A activity was measured in leukocyte homogenates by spectrophotometry (lambda = 515 nm) using p-nitrocatechol sulfate as chromogenic substrate. RESULTS: Frequency of N350S mutation and mutation 1524+95 A-->G was estimated at 6.8 and 2.8% for healthy controls, 11 and 5.5% for Alzheimer-type dementia, and 12 and 9.5% for Down syndrome, respectively. Arylsulfatase A activity was slightly but not significantly decreased in leukocytes derived from subjects with dementia and Down syndrome in comparison with age-matched control samples. CONCLUSIONS: Frequency of two mutations associated with ASA pseudodeficiency in the Croatian population is slightly below the range reported for other populations. Additionally, despite the proposed role of arylsulfatase A pseudodeficiency as one of the predisposing factors for neuropsychiatric disorders, our preliminary results did not show significantly higher frequencies of either mutation in Alzheimer-type dementia or Down syndrome.     

FISH在唐氏综合征产前诊断中的应用价值

目的:探讨荧光原位杂交(FISH)技术在唐氏综合征产前诊断中的应用价值。方法:采用位点特异性探针(DSCR2)对40例羊水细胞和10例绒毛细胞标本进行未培养间期细胞FISH实验。结果:检测出患儿2例,其中1例为标准21三体,1例为嵌合体。检测结果与染色体核型分析及随访相符。结论:FISH技术应用于产前诊断唐氏综合征,具有快速、准确的优势,并且可使诊断时间提早到孕50～70d,在高危孕妇的产前筛查中具有良好的应用前景。     

Maternal serum screening for Down syndrome in a teaching hospital in Hong Kong

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孕中期胎儿唐氏综合征筛查效率与筛查孕周选择

目的研究在不同孕周进行唐氏综合征血清学筛查是否存在效率差异,并探讨筛查的最佳孕周段。方法回顾性分析2005至2007年绍兴地区36309例孕妇孕中期（15-20周）母血清AFP／Free-β-hCG的二联产前筛查、染色体核型分析及随访资料,比较不同孕周组和孕周段的检出率及假阳性率。结果所有筛查孕妇中提示高风险的有2050例,其中确诊为唐氏综合征10例,在孕15周漏诊1例;总检出率为90.91％,总假阳性率为5.62％。17及18孕周组假阳性率为3.65％,显著低于其他孕周组（均P〈0.01）;16-18孕周段检出率为100％,假阳性率为4.50％,明显优于其它孕周段。结论在现有孕中期母血清AFP／Free-β-hCG二联体系下进行唐氏综合征筛查,16-18孕周段可能为最佳筛查时期。     

叶酸代谢关键酶基因多态性与唐氏综合征发生关系的研究

目的 研究叶酸代谢中关键酶亚甲基四氢叶酸还原酶基因(MTHFR C677T)及蛋氨酸合成酶还原酶基因(MTRRA66G)多态性与唐氏综合征发生的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法对32例唐氏综合征患儿母亲及70例未生育该种患儿的女性MTHFR C677T、MTRR A66G进行基因分析.比较各组基因型和等位基因频率分布有无差异.结果 MTHFR C677T突变型等位基因(T)频率,MTRR A66G突变型等位基因(G)频率在实验组和对照组中有显著性差异,CC、TT、GG基因型频率分布差异有显著性意义(P＜0.05).结论 MTHFR C677T、T677T基因型、MTRR G66G基因型增加了唐氏综合征的发生风险,MTHFR C677C基因型可能是降低唐氏综合征发生的保护性因素.     

DSA与MRA在Moyamoya病的诊断价值

目的:探讨数字减影血管造影(DSA)与磁共振血管造影术(MRA)对Moyamoya病的诊断价值。方法:12例Moyamoya病患者均行MRA检查,10例行DSA检查。结果:全部病例在MRA图像上均显示颈内动脉分叉以上狭窄或闭塞,在颅脑基底部侧支循环明显异常增多,呈烟雾状血管网;全脑DSA表现为颈内动脉分叉以上大动脉前、中动脉近段狭窄和闭塞,颅底异常增多的血管网及通过侧支循环建立的吻合支显示更为清晰。讨论:MRA作为一种无创伤血管成像技术能准确诊断Moyamoya病,儿童最为适用;DSA在显示细节如烟雾血管、侧支循环血管等方面优于MRA。     

烟雾病患者颅内主干型动脉瘤的血管内治疗

目的 总结血管内治疗烟雾病患者颅内主干型动脉瘤的临床体会.方法 13例蛛网膜下腔出血患者影像学证实为烟雾病合并颅内主干型动脉瘤,对13例颅内动脉瘤采用单纯弹簧圈栓塞、球囊辅助弹簧圈栓塞和支架辅助弹簧圈栓塞的方法进行治疗.结果 13例患者均成功治疗,动脉瘤完全填塞11例,90%以上填塞2例.所有载瘤动脉通畅,临床效果优良.结论 血管内栓塞是烟雾病患者颅内主干型动脉瘤的有效治疗方法,但长期疗效有待进一步随访.     

中晚孕期超声筛查唐氏综合征的价值

目的探讨中晚孕期超声筛查唐氏综合征(Down syndrome,DS)的价值。方法回顾分析经羊水或脐血染色体分析确诊为唐氏综合征的32例胎儿的产前系统超声表现。结果 32例唐氏综合征中,超声检出鼻骨发育不良29例,持续伸舌28例,小指中节指骨缺如3例,脐动脉S/D升高13例,肱骨股骨短小9例,颈后皮肤皱褶(NF)增厚9例,胃十二指肠扩张7例,先天性心脏病6例;每例唐氏综合征均有2项以上的不同超声软指标异常表现,尤其以鼻骨异常及持续伸舌阳性率最高,分别为90.63%、87.50%。系统超声筛查唐氏综合征敏感性为96.88%。结论唐氏综合征胎儿中晚孕期可有多项超声改变,其中鼻骨异常及持续伸舌是最常见的表现。     

鼻前软组织厚度产前筛查唐氏综合征的临床价值

目的 通过超声检测胎儿鼻前软组织厚度(PT),探讨鼻前软组织厚度与唐氏综合征(DS)的关系,建立超声软指标PT中位倍数(MoM)值,明确PT筛查唐氏综合征的临床价值。 方法 对2012年6月—2014年6月期间在温州市中心医院超声检查的孕16～25周的正常胎儿及DS胎儿进行PT测量,组间比较采用t检验或Wilcoxon秩和检验,并行Spearman线性相关分析,采用二次回归模型计算2组MoM(PT)值,并建立风险评估模型,观察敏感度、特异度、阳性预测值、阴性预测值、阳性似然比、阴性似然比指标。 结果 正常组PT平均值为(3.51±0.91) mm,DS组PT平均值为(5.16±0.79) mm,差异有统计学意义(t=12.23,P＜0.05);正常组胎儿PT随孕周增加而增厚,正常胎儿PT的MoM值为1.010,DS胎儿PT的MoM值为1.371。PT为单一指标筛查DS,以5%假阳性率,筛查唐氏综合征胎儿敏感度为58%,阳性预测值为0.46,阴性预测值为0.97,阳性似然比为11.63,阴性似然比为0.44;PT联合年龄高风险筛查DS,以5%假阳性率,敏感度提高到75%,阳性预测值为0.52,阴性预测值为0.98,阳性似然比为14.94,阴性似然比为0.26。 结论 鼻前软组织厚度是孕中期筛查唐氏综合征有效的遗传学超声软指标,唐氏综合征胎儿鼻前软组织厚度较正常胎儿厚。鼻前软组织厚度联合年龄高风险筛查唐氏综合征可以提高筛查敏感度,风险截断值达1/250,应建议行侵入性检查。      

Down syndrome and the molecular pathogenesis resulting from trisomy of human chromosome 21

Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in anueploidy. Victor Tybulewicz is an immunologist whose primary interest is in signal transduction from the antigen receptors of B and T cells.