Rubinstein-Taybi syndrome and hypoplastic left heart
Rubinstein-Taybi syndrome and hypoplastic left heart
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DOI：
10.1002/ajmg.10617
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发表时间：
2002-09-15
期刊：
影响因子：
--
通讯作者：
Wallerstein, R
中科院分区：
文献类型：
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作者：
Hanauer, D;Argilla, M;Wallerstein, R
Rubinstein-Taybi综合征（RTS）是由16p13染色体上cAMP反应元素结合蛋白（CREB）结合蛋白（CBP）基因的各种突变和缺失引起的，以拇指和脚趾宽、生长缺陷、特征相和认知缺陷为特征的多发性先天性异常/智力低下综合征。[Wallerstein et al., 1997]。先天性心脏缺陷发生率高达33%的RTS患者[Stevens and Bhatka， 1995]。最常见的心脏缺损是动脉导管未闭（PDA）、室间隔缺损（VSD）和房间隔缺损（ASD）。最近，我们评估了一名左心发育不全的婴儿，他也有RTS的临床特征。对医学文献的回顾显示，RTS患者中还有另外两例左心发育不全的报道，这表明这种心脏病变在该综合征中并不常见。患者母亲30岁，既往无明显病史。左心发育不全（HLH）是在妊娠20周常规产前超声检查中发现的。母体血清三重筛检及羊膜穿刺术正常。还有另外两个健康的孩子。家族史对患有“心脏肿大”需要瓣膜置换的祖父，以及患有心脏起搏器的祖父的曾祖母和曾祖父都具有重要意义。该婴儿在妊娠38 6/7周时通过选择性剖宫产出生。出生时的评估显示初始心率低于80次/分，对短暂的正压通气反应迅速。Apgar评分在1分钟时为8分，在5分钟时为8分。婴儿被注意到有畸形特征，包括突出的鼻子，有片状小鼻，轻微的小颌，发育不良的耳朵，宽间距的乳头，深足底皱纹，宽而偏的拇指，关节异常，大脚趾也很宽但没有偏。临床诊断为Rubinstein-Taybi综合征。染色体研究在550波段水平显示正常46，XY核型。用cosmid探针RT1 （D16S237）进行荧光原位杂交（FISH）显示了两个正常的杂交信号，没有16p13缺失的证据。3轨迹。超声心动图证实HLH伴有二尖瓣闭锁、主动脉发育不全、单冠状动脉起源、ASD、单右心室和大PDA（图1和2）。腹部超声未见局灶性异常，颅脑超声示左侧脉络膜丛2个小（2mm）囊肿，未见脑室内出血或脑积水。胸片显示双侧肺野模糊。家长选择姑息性手术治疗HLH。术前给予前列腺素、地高辛和速尿输注；避免使用补充氧。在生命的第五天，婴儿接受了姑息性手术（诺伍德程序），但在术中死亡。没有进行尸检，也没有给病人拍照。左心发育不全包括左心房和左心室发育不全，主动脉和/或二尖瓣口闭锁，升主动脉发育不全。这种缺陷依赖于右心室提供肺循环和体循环，通常导致体循环维持不足，导致肺静脉高压或肺过度循环[Bernstein， 1996]。HLH是新生儿期心脏性死亡的最常见原因，占生命第一年所有心脏性死亡的25% [Harris， 2000]。治疗方案的各种…
Rubinstein-Taybi syndrome (RTS) is a multiple congenital anomaly/mental retardation syndrome characterized by broad thumbs and toes, growth deficiency, characteristic facies, and cognitive defects that are caused by various mutations and deletions of the cAMP response element-binding protein (CREB)-binding protein (CBP) gene on chromosome 16p13. 3 [Wallerstein et al., 1997]. Congenital heart defects occur in up to 33% of RTS individuals [Stevens and Bhatka, 1995]. The most commonly reported cardiac defects are patent ductus arteriosus (PDA), ventricular septal defect (VSD), and atrial septal defect (ASD). Recently, we evaluated an infant with hypoplastic left heart who also had clinical features of RTS. Review of the medical literature shows two other reported cases of hypoplastic left heart in RTS patients, suggesting that this cardiac lesion is a less common association of this syndrome. The patient’s mother was 30 years old with no significant past medical history. Hypoplastic left heart (HLH) was discovered at 20 weeks gestation during a routine prenatal ultrasound. The maternal serum triple screen and amniocentesis were normal. There were two other healthy children. The family history was significant for a paternal grandfather with an ‘‘enlarged heart’’who required a valve-replacement, and a paternal greataunt and great-uncle who both had pacemakers. The infant was born at 38 6/7 weeks gestation via an elective cesarean section. Evaluation at birth showed an initial heart rate of less than 80 beats/min, which quickly responded to brief positive pressure ventilation. Apgar scores were 8 at one min and 8 at five min. The infant was noted to have dysmorphic features including prominent nose with a sheet columella, mild micrognathia, dysplastic ears, widely-spaced nipples, deep plantar creases, broad and deviated thumbs that were abnormally articulated, and great toes that were also broad but without deviation. Based on the physical findings a clinical diagnosis of Rubinstein-Taybi syndrome was made. Chromosome studies at the 550 band level showed a normal 46, XY karyotype. Fluorescent in situ hybridization (FISH) with the cosmid probe RT1 (D16S237) showed two normal hybridization signals without evidence of a deletion at the 16p13. 3 locus. Echocardiography confirmed HLH with mitral atresia, aortic hypoplasia, single coronary artery origin, ASD, single right ventricular chamber, and a large PDA (Figs. 1 and 2). Abdominal ultrasound showed no focal abnormalities and cranial ultrasound showed two small (2-mm) cysts in the left choroid plexus, without evidence of intraventricular hemorrhage or hydrocephalus. A chest radiograph showed bilateral hazy lung fields. The parents elected palliative surgery for HLH. Preoperatively the infant was maintained on a prostaglandin infusion, digoxin, and furosemide; use of supplemental oxygen was avoided. On the fifth day of life the infant underwent palliative surgery (Norwood procedure) but died intraoperatively. An autopsy was not performed and a photograph of the patient was not taken. Hypoplastic left heart includes underdevelopment of the left atrium and ventricle, atresia of the aortic and/or mitral orifice, and hypoplasia of the ascending aorta. Such a defect relies on the right ventricle to provide both pulmonary and systemic circulation, usually resulting in inadequate maintenance of systemic circulation and either pulmonary venous hypertension or pulmonary over-circulation [Bernstein, 1996]. HLH is the most common cause of cardiac death in the neonatal period and accounts for up to 25% of all cardiac deaths in the first year of life [Harris, 2000]. Treatment options for the various …