Comprehensive clinical studies in 34 patients with molecularly defined UPD(14)pat and related conditions (Kagami-Ogata syndrome).
Comprehensive clinical studies in 34 patients with molecularly defined UPD(14)pat and related conditions (Kagami-Ogata syndrome).
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DOI：
10.1038/ejhg.2015.13
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发表时间：
2015-11
期刊：
影响因子：
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通讯作者：
Ogata T
中科院分区：
文献类型：
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作者：
Kagami M;Kurosawa K;Miyazaki O;Ishino F;Matsuoka K;Ogata T
父亲单亲二体14（UPD（14）pat）和影响母亲来源的14q32.2印迹区域的表位突变和微缺失导致一系列独特的临床特征，如面部畸形，小钟形胸部伴肋骨衣架外观，腹壁缺陷，胎盘肿大和羊水过多。在这项研究中，我们对UPD（14）pat（n=23），表型突变（n=5）和微缺失（n=6）患者进行了全面的临床研究，并揭示了几个值得注意的结果。首先，从婴儿期到儿童期，独特的面部外观（面颊饱满，人中突出）和独特的胸部X线片（与肋骨的衣架角增加）构成了特征性特征。第二，出生体尺保存良好，中位出生身长为±0 SD（范围：-1.7至+3.0 SD），中位出生体重为+2.3 SD（范围：+0.1至+8.8 SD）。第三，发育迟缓和/或智力残疾总是存在，发育/智力商数中位数为55（范围，29-70）。第四，肝母细胞瘤被确定在三个婴儿患者（8.8%），和两名患者的组织学检查显示低分化胚胎肝母细胞瘤局灶性大小梁病变和分化良好的肝母细胞瘤，分别。这些发现提示有必要对受影响的患者进行发育延迟和肝母细胞瘤的定期筛查，以及UPD（14）pat和相关疾病与Beckwith-Wiedemann综合征之间的某些表型重叠。基于我们之前和现在的研究，这些研究对阐明潜在（表观）遗传因素和临床发现的定义做出了重大贡献，我们建议将UPD（14）pat和相关疾病命名为“Kagami-Ogata综合征”。
Paternal uniparental disomy 14 (UPD(14)pat) and epimutations and microdeletions affecting the maternally derived 14q32.2 imprinted region lead to a unique constellation of clinical features such as facial abnormalities, small bell-shaped thorax with a coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly, and polyhydramnios. In this study, we performed comprehensive clinical studies in patients with UPD(14)pat (n=23), epimutations (n=5), and microdeletions (n=6), and revealed several notable findings. First, a unique facial appearance with full cheeks and a protruding philtrum and distinctive chest roentgenograms with increased coat-hanger angles to the ribs constituted the pathognomonic features from infancy through childhood. Second, birth size was well preserved, with a median birth length of ±0 SD (range, −1.7 to +3.0 SD) and a median birth weight of +2.3 SD (range, +0.1 to +8.8 SD). Third, developmental delay and/or intellectual disability was invariably present, with a median developmental/intellectual quotient of 55 (range, 29–70). Fourth, hepatoblastoma was identified in three infantile patients (8.8%), and histological examination in two patients showed a poorly differentiated embryonal hepatoblastoma with focal macrotrabecular lesions and well-differentiated hepatoblastoma, respectively. These findings suggest the necessity of an adequate support for developmental delay and periodical screening for hepatoblastoma in the affected patients, and some phenotypic overlap between UPD(14)pat and related conditions and Beckwith–Wiedemann syndrome. On the basis of our previous and present studies that have made a significant contribution to the clarification of underlying (epi)genetic factors and the definition of clinical findings, we propose the name ‘Kagami–Ogata syndrome' for UPD(14)pat and related conditions.