Friday, September 9, 2011
Wednesday, August 17, 2011
Beckwith-Wiedemann syndrome (BWS)
这是BWS的资料。 这份非常深入，是给我自己留的。
Beckwith-Wiedemann syndrome(BWS) is an overgrowth syndrome characterized by macrosomia, macroglossia, omphalocele, hemihyperplasia, and increased tumor risk.
BWS can be associated with genetic and/or epigenetic alterations that modify imprinted gene expression on chromosome 11p15.5.
Somatic mosaicism for paternal uniparental disomy (UPD) of chromosome 11p15, found in 20% of BWS patients, is associated with specific features of BWS including hemihyperplasia, Wilms tumor, and hepatoblastoma.
The highly variable phenotypic spectrum of BWS associated with UPD may well reflect the level of UPD 11 cells in specific organs and tissues such that very high levels of UPD might produce a more severe phenotypic expression of BWS.
Beckwith Wiedemann syndrome (BWS) involves the deregulation of a number of genes, including IGF2 and CDKN1C, in the imprinted gene cluster on chromosome 11p15.5.
In sporadic BWS cases the majority of patients have epimutations in this region. Loss of imprinting of the IGF2 gene is frequently observed in BWS, as is reduced CDKN1C expression related to loss of maternal allele-specific methylation (LOM) of the differentially methylated region KvDMR1.
The causes of epimutations are unknown. To date the only genetic mutations described in BWS are in the CDKN1C gene.
Epidemiology
Frequency: 0.8% (USA)
Risk factors
in vitro fertilization and assisted reproductive technology (ART) (4.6% vs 0.8% USA) (12439823)
Synopsis
cardiac anomalies
visceromegaly (unilateral or bilateral)
hepatic anomalies in BWS
adrenal anomaies in BWS
adrenal heterotopia
renal anomalies in BWS (42%) (12138139)
persistent hyperinsulinemic hypoglycemia (11441340)
infantile hamartomas
macroglossia
omphalocele
umbilical hernia
diaphragmatic hernia (15517831)
extralobar lung sequestration (15517831)
hemihypertrophy
Tumor predisposition (4-21%) (15887271)
Patients with Beckwith-Wiedemann syndrome (BWS) have a risk of 7.5% to 10% of developing childhood tumors, 60% of which are Wilms’ tumors.
vascular dysplasias (vascular malformations)
Increased tumour risk
Aberrant methylation of two distinct clusters of imprinted genes on chromosome 11p15 is detected in approximately 70% of BWS cases.
sequence variants in the IGF2 gene (14645199)
loss of imprinting of the IGF2 gene
reduced CDKN1C expression related to loss of maternal allele-specific methylation (LOM) of the differentially methylated region KvDMR1
germline mutations in the CDKN1C gene (MIM.600856) at 11p15.5
germline mutations in the NSD1 gene (MIM.606681) at 5q35
See also
overgrowth syndromes
Beckwith-Wiedemann syndrome(BWS) is an overgrowth syndrome characterized by macrosomia, macroglossia, omphalocele, hemihyperplasia, and increased tumor risk.
BWS can be associated with genetic and/or epigenetic alterations that modify imprinted gene expression on chromosome 11p15.5.
Somatic mosaicism for paternal uniparental disomy (UPD) of chromosome 11p15, found in 20% of BWS patients, is associated with specific features of BWS including hemihyperplasia, Wilms tumor, and hepatoblastoma.
The highly variable phenotypic spectrum of BWS associated with UPD may well reflect the level of UPD 11 cells in specific organs and tissues such that very high levels of UPD might produce a more severe phenotypic expression of BWS.
Beckwith Wiedemann syndrome (BWS) involves the deregulation of a number of genes, including IGF2 and CDKN1C, in the imprinted gene cluster on chromosome 11p15.5.
In sporadic BWS cases the majority of patients have epimutations in this region. Loss of imprinting of the IGF2 gene is frequently observed in BWS, as is reduced CDKN1C expression related to loss of maternal allele-specific methylation (LOM) of the differentially methylated region KvDMR1.
The causes of epimutations are unknown. To date the only genetic mutations described in BWS are in the CDKN1C gene.
Epidemiology
Frequency: 0.8% (USA)Risk factors
in vitro fertilization and assisted reproductive technology (ART) (4.6% vs 0.8% USA) (12439823)Synopsis
cardiac anomalies- excess of cardiac malformation (15608459)
- epicardial angiofibroma (15608459)
- focal giant cell cardiomyopathy (4095024)
visceromegaly (unilateral or bilateral)- nephromegaly (tumoral risk factor) (9544890)
- hepatomegaly
- adrenomegaly
hepatic anomalies in BWS- focal nodular hyperplasia (15965690)
- hepatoblastoma predisposition (14692643, 12970646, 12721741, 10573588)
- biliary dysgenesis (proliferation of abnormally shaped ducts in the portal tracts) (2371181)
- mixed hamartoma of the liver (11441340)
- hepatic hemangioendotheliomas [1570237)
adrenal anomaies in BWS- adrenomegaly
- adrenal cytomegaly
- adrenal macrocyst (unilateral or bilateral) (15539867)
adrenal heterotopia- pulmonary adrenal heterotopia (6465087)
- heterotopic adrenal cortex with cytomegaly in lateral ventricle choroids plexus (17162526)
renal anomalies in BWS (42%) (12138139)- bilateral nephromegaly (25%)
- clusters of immature tubules (1570237)
- foci of dysplastic medullary ducts (1570237)
- collecting system abnormalities (11%)
- renal medullary dysplasia (17172498)
- renal cysts (10.5%)
- perilobar nephrogenic rests (perilobar nephroblastematosis)
- predisposition to Wilms tumor
persistent hyperinsulinemic hypoglycemia (11441340)- islet cell hyperplasia (endocrine pancreas hyperplasia) (11441340)
infantile hamartomas- mixed hamartoma of the liver (MHL) (11441340)
- left chest wall hamartoma (11424137)
- vesical hamartoma (hamartoma of the urinary bladder) (2310920)
- cardiac hamartoma (4343707)
macroglossia omphalocele umbilical hernia diaphragmatic hernia (15517831) extralobar lung sequestration (15517831) hemihypertrophyTumor predisposition (4-21%) (15887271)
Patients with Beckwith-Wiedemann syndrome (BWS) have a risk of 7.5% to 10% of developing childhood tumors, 60% of which are Wilms’ tumors.
- Wilms tumor
- hepatoblastoma
- neuroblastoma
- embryonal rhabdomyosarcoma (11826361)
- corticoadrenal adenoma and corticoadrenal carcinoma
- angiofibroma (15608459)
- hemangiomas
- splenic hemangioma (9094248)
- multiple hepatic hemangioendotheliomas (1570237)
- placental chorangioma (10191350)
- juvenile hemangioma (15509684)
vascular dysplasias (vascular malformations)- nevus flammeus (11424137)
- large congenital arteriovenous malformations (AVM) (17162526)
Increased tumour risk- hemihypertrophy
- nephromegaly (9544890)
- aberrant H19 and not KCNQ1OT1 methylation (11181570, 15580204)
Aberrant methylation of two distinct clusters of imprinted genes on chromosome 11p15 is detected in approximately 70% of BWS cases.
sequence variants in the IGF2 gene (14645199) loss of imprinting of the IGF2 gene reduced CDKN1C expression related to loss of maternal allele-specific methylation (LOM) of the differentially methylated region KvDMR1 germline mutations in the CDKN1C gene (MIM.600856) at 11p15.5 germline mutations in the NSD1 gene (MIM.606681) at 5q35See also
overgrowth syndromes
第一个好消息
第一个好消息 8月17日
今早醒来，乎然觉得有了些信心， 或者是昨晚念了一晚经 求观音娘娘给我指示。 从内心深处感觉得到小豆不会有trisomies的问题。唯一让我担心的是Beckwith-Wiedemann Syndromes.
早上带了小毛去看医生； 近来他常在睡觉中流鼻血， 我们用竟了办法都不能阻止鼻血半夜的来临。据医生说可能是空气里的ragweed花粉过敏造成鼻子里的血管inflammation。 不过她肯定不是leukemia。 她确定让小毛验血to rule out Von Willibrand’s disease。 小毛的健康让我松了口气。
下午，Perinatalogist 的护士来电带来了第一个好消息， 小豆的trisomy 13，18，21 都完整，正确，没问题。其他的得等两个星期才知道。娘娘请报佑小豆，让好消息陆续而来。
晴天霹雳。。。。。
晴天霹雳 8月16日
我与哈呢， 个别都有梦过我们会两个孩子。他甚至知道是 两个男孩。 他很肯定 那第 二个是个开心果。我们面对infertility 的问题多年， 好不容易得到了毛一， 但两个月后却掉了它。后来数月后得了小毛。 那时我是怀着战战兢兢的心情， 一直怕不见了他。小毛是顺顺利利的诞生了，虽然有些惊心动魄的事，但还算母子平安。
到了这胎， 我想我应该相信我们的梦， 什么也不想， 充满信心的， 愉愉快快的怀这胎。我是高龄产妇加上我的超大uterus fibroid, 医生是安排我每四个期做定期ultrasound sonogram 来肯定胎儿的成长。昨日我们一家抱着期待又紧张的心情去看小豆豆。一开始便看到小豆豆是个男孩， 哈呢的梦灵了(虽然他想要个女儿)。我可是无所谓，我已有了我要的儿子。 再下来， 看了他的脸，胖都都的，瞒可爱的。再下去，在他的腹部上头好象多了一块东西。医生的脸色也变了。他看了数分钟，最后宣布这是 omphalocele. 小豆的肠藏有部份留在体外，这可大可小。小的是只是肠在外，但这也可能是genetic的问题，那问题就大了。他的其他器官也可能有影响，如心胀，肺，肾等等。
晴天霹雳！！！为甚么上天从未提告我们此事。我们只梦过小豆会来，梦过他开朗，聪明，但从未梦过他有健康问题。这是小豆吗？或许我做错了什么事，把我们的命运都变了。我的心碎了。我一时也不知该如何做决定。医生劝我做amniocentasis来测看是不是genetic problems, 尤其是trisomies 18，13，21。然后再测心藏。我一向反对这test，因为它有1-2成的miscarriage可能性。但如果小豆已有问题，不如听天由命，知道好过不知道。两个礼拜后再见医生拿测验报告。我回到家搬出电脑，对了它整天整夜，读了所有有关它的资料，知道此事非同凡响，无论如何都要heavy medical treatment约一年左右。我们该如何是好??
Friday, July 1, 2011
我的小美人
妈妈懒， 爸爸因某些因由不可煮， 我们一家三口便绕了整个Overland Park一周为了找个地方糊口。 最后来到家韩国店随便吃点韩国面。
这是间小店， 里边才不过十张台。 我们到时有一台看似公公婆婆与爸妈和两个小孩。 大的孩子跟小毛年纪相仿， 小的是个小女婴看来不过两个月大。里边还有两个小孩女是老板的孙女， 小的那个记得比小毛大半岁。小毛进来向周围看了看，让Daddy 与Mommy下了定，便拉着daddy的手往外走， 要到外边去溜达。他一向坐不文， 如果不让他走走， 把他的耐性用竟后， 当食物来时， 他便坐不下来吃。
当食物上桌时， 有一对夫妇拿着婴儿篮刚进来。小毛正专心吃着妈妈的udon面。 当他们点了单，那年轻爸爸把那女婴抱出来， 远远望去那女孩看来还蛮精致， 圆圆乌溜溜的大眼睛， 巧巧的鼻子， 樱桃般的小嘴， 可爱极了。小毛不小心看到了， 他马上跳起来， 启徒爬过我身子。 问他“饱饱了吗?”， 他不肯说， 但肯吃多一口便跳下去了。 一般上， 他比较喜欢跟大人打交道， 但这回他是先跟那女孩招手， 然后再跟她父母招手。在一般人眼里只觉得他非常喜欢小孩，但我看了有点不解。 再看他在那女孩前手舞脚蹈的， 才明白过来， 他是在讨那女孩的欢心。我晕！这么小以会扣女了。 更好笑得是那爸爸已开始紧张起来， 忙说“no boys， no boys“ 。 我简直是笑得仰天伏地。我的小毛一定不搞gay， 一定是个小色鬼。
这是间小店， 里边才不过十张台。 我们到时有一台看似公公婆婆与爸妈和两个小孩。 大的孩子跟小毛年纪相仿， 小的是个小女婴看来不过两个月大。里边还有两个小孩女是老板的孙女， 小的那个记得比小毛大半岁。小毛进来向周围看了看，让Daddy 与Mommy下了定，便拉着daddy的手往外走， 要到外边去溜达。他一向坐不文， 如果不让他走走， 把他的耐性用竟后， 当食物来时， 他便坐不下来吃。
当食物上桌时， 有一对夫妇拿着婴儿篮刚进来。小毛正专心吃着妈妈的udon面。 当他们点了单，那年轻爸爸把那女婴抱出来， 远远望去那女孩看来还蛮精致， 圆圆乌溜溜的大眼睛， 巧巧的鼻子， 樱桃般的小嘴， 可爱极了。小毛不小心看到了， 他马上跳起来， 启徒爬过我身子。 问他“饱饱了吗?”， 他不肯说， 但肯吃多一口便跳下去了。 一般上， 他比较喜欢跟大人打交道， 但这回他是先跟那女孩招手， 然后再跟她父母招手。在一般人眼里只觉得他非常喜欢小孩，但我看了有点不解。 再看他在那女孩前手舞脚蹈的， 才明白过来， 他是在讨那女孩的欢心。我晕！这么小以会扣女了。 更好笑得是那爸爸已开始紧张起来， 忙说“no boys， no boys“ 。 我简直是笑得仰天伏地。我的小毛一定不搞gay， 一定是个小色鬼。
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