Ohtake Akira, Aoki Yoko, Saito Yuka, Niihori Tetsuya, Shibuya Atsushi, Kure Shigeo, Matsubara Yoichi
Department of Pediatrics, Saitama Medical University, Moroyama, Saitama, Japan.
J Pediatr Hematol Oncol. 2011 Dec;33(8):e342-6. doi: 10.1097/MPH.0b013e3181df5e5b.
Cardiofaciocutaneous (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. Mutations in KRAS, BRAF, and MAP2K1/2 (MEK1/2) have been identified in patients with CFC syndrome. BRAF mutations are involved in more than 80% of CFC syndrome patients, and we have reported earlier that 2 CFC patients with BRAF mutations developed acute lymphoblastic leukemia. Here we report a boy with CFC syndrome who developed non-Hodgkin lymphoma. At 2 months of age, he developed pneumonia with pleurisy and was diagnosed as having non-Hodgkin lymphoma (precursor T-cell lymphoblastic lymphoma) by cytopathologic examination of the pleural fluid. He was suspected of having Noonan syndrome because of his facial appearance, webbed neck, and cubitus valgus. Precursor T-cell lymphoblastic lymphoma was treated by the TCCSG NHL 94-04 protocol. At 9 years of age, he was clinically reevaluated and diagnosed as having CFC syndrome because of his distinctive facial appearance, multiple nevi, and moderate mental retardation. Sequencing analysis showed a germline p.A246P (c.736G>C) mutation in BRAF reported earlier in CFC syndrome. Molecular diagnosis and careful observation should be considered in children with CFC syndrome.
心脏颜面皮肤综合征（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。在CFC综合征患者中已鉴定出KRAS、BRAF和MAP2K1/2（MEK1/2）的突变。BRAF突变在超过80%的CFC综合征患者中出现，我们之前曾报道2例携带BRAF突变的CFC患者患急性淋巴细胞白血病。在此，我们报告1例患有CFC综合征并发生非霍奇金淋巴瘤的男孩。2个月大时，他患肺炎伴胸膜炎，通过胸水细胞病理学检查被诊断为非霍奇金淋巴瘤（前体T细胞淋巴母细胞淋巴瘤）。由于其面部外观、蹼颈和肘外翻，他曾被怀疑患有努南综合征。前体T细胞淋巴母细胞淋巴瘤采用TCCSG NHL 94 - 04方案进行治疗。9岁时，因其独特的面部外观、多发性痣和中度智力发育迟缓，经临床重新评估被诊断为CFC综合征。测序分析显示存在BRAF基因种系p.A246P（c.736G>C）突变，该突变在之前的CFC综合征报道中已有提及。对于CFC综合征患儿，应考虑进行分子诊断并仔细观察。
