Pachygyria and cerebellar hypoplasia in Goldberg–Shprintzen syndrome
Pachygyria and cerebellar hypoplasia in Goldberg–Shprintzen syndrome
复制标题
Goldberg-Shprintzen 综合征中的脑回肥大和小脑发育不全
DOI：
10.1002/ajmg.a.20013
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发表时间：
2003
影响因子：
2
通讯作者：
F. Papalia
中科院分区：
文献类型：
--
作者：
M. Silengo;G. Ferrero;L. Tornetta;M. Cortese;F. Canavese;G. D'alonzo;F. Papalia
Goldberg和Shprint tzen[1981]报告了两个患有短段性先天性巨结肠症、小头畸形、智力低下和明显面部外观的兄弟姐妹，包括端头过长。到目前为止，文献中已报道了11例散发病例[Brunoni等人，1983；Breslau和Laan，1989；Halal和Morel，1990；Tanaka等人，1993；Ohnuma等人，1997；Mowat等人，1998]和总共17个家族性病例的7组同胞[Goldberg和Shprint tzen，1981；Hurst等人，1988；Kumasaka和Clarren，1988；Yomo等人，1991；Fryer，1998；Brooks等人，1999]。该综合征的遗传被认为是常染色体隐性遗传(MIM 235730)，但已经提出了遗传异质性，零星病例可能具有邻近基因综合征或从头显性突变[Wakamatsu等人，2001年]。Ohnuma等人。[1997]在本杂志中首次描述了一例Goldberg-Shprint tzen综合征患者的磁共振成像(MRI)异常。异常改变为脑发育不良、实质体积减少，尤其是白质内，以及包括无嘴、膝和压部在内的穹隆发育不良。我们报告一位Goldberg-Shprint tzen综合征患者，他的MRI表现新颖，包括大脑回和古新小脑发育不良，这表明在该综合征中观察到的迁移缺陷不仅涉及神经脊细胞，而且还涉及神经元。患者是在一次简单的怀孕后，在怀孕38周时由健康的、非血缘关系的父母生下的。出生体重2600g，身长46 cm，头围31 cm(均低于胎龄平均值2SD)。由于严重的便秘和腹胀，在围产期被怀疑为巨结肠。在手术中，诊断出一种短段型先天性巨结肠，延伸至肛门-直肠交界处上方几厘米。组织学检查显示肌间神经丛和粘膜下神经丛无神经节细胞增多。婴儿有畸形的面部特征，如额头倾斜，眉毛稀疏，眼球过长(ICD 27 mm，OCD 52 mm)，鼻梁凹陷，鼻球状，嘴唇丰满(图1)。眼科检查发现视盘苍白，缺乏注视，眼球运动异常。视觉诱发电位反应减弱，而听觉诱发电位大体正常。脑部核磁共振显示大脑回、胼胝体发育不良、蚯蚓和小脑半球发育不良(图2)。高分辨(800条)核型为正常46，XY。Miller-Dieker探针的FISH分析显示17p末端缺失为阴性。突变分析为阴性。在新发现的SIP1基因中发现突变。4个月时随访发现严重发育迟缓、脑电异常和小头畸形(头围36.5，低于3百分位数)。有几个基因可能与孤立和综合征性先天性巨结肠症有关，如RET、GDNF、EDN3和EDNRB。它们的突变导致胚胎发育过程中神经脊细胞的发育和迁移受到干扰[Seri等人，1997]。ShahWaardenburg综合征(WS4)是一种罕见的神经软骨病变，由黑素细胞缺乏和
Goldberg and Shprintzen [1981] reported two sibs with short-segment Hirschsprung disease, microcephaly, mental retardation, and a distinct facial appearance, including hypertelorism. Up to now, 11 sporadic cases [Brunoni et al., 1983; Breslau andLaan, 1989;Halal and Morel, 1990; Tanaka et al., 1993; Ohnuma et al., 1997; Mowat et al., 1998] and 7 sets of sibs for a total of 17 familial cases [Goldberg and Shprintzen, 1981; Hurst et al., 1988; Kumasaka and Clarren, 1988; Yomo et al., 1991; Fryer, 1998; Brooks et al., 1999] have been reported in the literature. Inheritance of the syndrome is thought to be autosomal recessive (MIM 235730), but genetic heterogeneity has been suggested with sporadic cases possibly having contiguous genes syndromes or de novo dominant mutations [Wakamatsu et al., 2001]. Ohnuma et al. [1997] first described in this Journal themagnetic resonance imaging (MRI) abnormalities in a patient affected by the Goldberg–Shprintzen syndrome. Brain hypoplasia, loss of parenchymal volume, especially in the white matter, hypoplasia of the corpus callosum including absent rostrum, genu and splenium, were the abnormal changes observed. We report a patient with the Goldberg–Shprintzen syndrome who presents novel MRI findings including pachygyria and paleo-neocerebellar hypoplasia, suggesting that the migration defect observed in the syndrome involves not only the neural crest cells but also the neurons. The patient was born to healthy, nonconsanguineous parents at 38 weeks of gestation after an uncomplicated pregnancy. Birth weight was 2600 g, length 46 cm, head circumference 31 cm (all parameters 2SD below the mean for gestational age). A diagnosis of megacolon was suspected in the perinatal period because of severe constipation and abdominal distension. At surgery, a short segment typeHirschsprung disease, extending for few centimeters above the ano-rectal junction, was diagnosed. Aganglionosis of the myenteric and submucosal plexus was demonstrated on histological examination. The infant had dysmorphic facial features such as sloping forehead, sparse eyebrows, ocularhypertelorism (ICD 27 mm, OCD 52 mm), depressed nasal bridge, bulbous nose, and full lips (Fig. 1). The ophthalmologic examination revealed pale optic disks, lack of fixation and abnormal eyemovements. The visual evoked potentials yielded reduced responses, while the auditory evoked potentials were grossly normal. A brain MRI showed pachygyria, hypoplasia of the corpus callosum and hypoplasia of the vermis and cerebellar hemispheres (Fig. 2). The high resolution (800 bands) karyotype was normal 46,XY. FISH analysis with the Miller-Dieker probe was negative for a distal 17p deletion. Analysis ofRETmutationswas negative. Nomutations in the newly identified SIP1 gene were found. Follow up at 4 months of age revealed severe developmental retardation, abnormal EEG, and microcephaly (head circumference 36.5, below the 3rd centile). Several genes are potentially involved in isolated and syndromic Hirschsprung disease, such as RET, GDNF, EDN3, and EDNRB. Their mutations result in disturbed development and migration of the neural crest cells during embryogenesis [Seri et al., 1997]. The ShahWaardenburg syndrome (WS4) is a rare neurochristopathy that results from the absence of melanocytes and
影响因子：
30.8
作者：
Wakamatsu, N;Yamada, Y;Nagaya, M
通讯作者：
Nagaya, M