Makita Yoshio, Narumi Yoko, Yoshida Makoto, Niihori Tetsuya, Kure Shigeo, Fujieda Kenji, Matsubara Yoichi, Aoki Yoko
Department of Pediatrics, Asahikawa Medical College, Asahikawa, Japan.
J Pediatr Hematol Oncol. 2007 May;29(5):287-90. doi: 10.1097/MPH.0b013e3180547136.
Cardio-facio-cutaneous (CFC) syndrome is a multiple congenital anomaly/mental retardation syndrome characterized by a distinctive facial appearance, ectodermal abnormalities, and heart defects. Clinically, it overlaps with both Noonan syndrome and Costello syndrome, which are caused by mutations in 2 genes that encode molecules of the RAS/MAPK (mitogen activated protein kinase) pathway (PTPN11 and HRAS, respectively). Recently, mutations in KRAS, BRAF, and MEK1/2 have been identified in patients with CFC syndrome. Somatic mutations in KRAS and BRAF have been identified in various tumors. In contrast, the association with malignancy has not been noticed in CFC syndrome. Here we report a 9-year-old boy diagnosed with CFC syndrome and acute lymphoblastic leukemia. Sequencing analysis of the entire coding region of KRAS and BRAF showed a de novo germline BRAF E501G (1502A-->G) mutation. Molecular diagnosis and careful observations should be considered in children with CFC syndrome because they have germline mutations in proto-oncogenes and might develop malignancy.
心脏-颜面-皮肤（CFC）综合征是一种多发性先天性异常/智力发育迟缓综合征，其特征为独特的面部外观、外胚层异常和心脏缺陷。临床上，它与努南综合征和科斯特洛综合征有重叠，后两者分别由编码RAS/丝裂原活化蛋白激酶（MAPK）信号通路分子的2个基因（分别为PTPN11和HRAS）发生突变所致。最近，在CFC综合征患者中发现了KRAS、BRAF和MEK1/2的突变。KRAS和BRAF的体细胞突变已在多种肿瘤中被发现。相比之下，CFC综合征与恶性肿瘤的关联尚未被注意到。在此，我们报告一名9岁男孩，他被诊断患有CFC综合征和急性淋巴细胞白血病。对KRAS和BRAF整个编码区的测序分析显示存在一种新发的胚系BRAF E501G（1502A→G）突变。对于患有CFC综合征的儿童，应考虑进行分子诊断和仔细观察，因为他们的原癌基因存在胚系突变，可能会发生恶性肿瘤。
