Al-Rahawan Mohamad M, Chute Deborah J, Sol-Church Katia, Gripp Karen W, Stabley Deborah L, McDaniel Nancy L, Wilson William G, Waldron Peter E
Department of Pediatrics,University of Virginia Health System, Charlottesville, Virginia.
Am J Med Genet A. 2007 Jul 1;143A(13):1481-8. doi: 10.1002/ajmg.a.31819.
Cardio-facio-cutaneous syndrome (CFC) and Costello syndrome (CS) are disorders with an overlapping spectrum of congenital anomalies. Mutations in the RAS-MAPK pathway have recently been reported in both of these syndromes, with HRAS mutations characteristic for CS and BRAF and MEK1/2 mutations for CFC. We report on a 3-year-old boy who underwent a cardiac transplant at age 8 months for hypertrophic cardiomyopathy; he was subsequently suspected to have CS. At age 35 months he presented with an intra-cardiac mass that was diagnosed as metastatic hepatoblastoma. Although hepatoblastoma is not known to have an increased frequency in immunocompromised patients, questions were raised as whether the post-transplant immuno-suppressive therapy played a role in tumor development. The patient died shortly thereafter and his post-mortem DNA analysis revealed a MEK1 mutation (Y130C) previously reported in CFC. While CS is associated with increased cancer risk, only a single case of leukemia has been reported in a patient with CFC, making this the first case of a solid tumor reported in a patient with CFC.
心脏-颜面-皮肤综合征（CFC）和科斯特洛综合征（CS）是先天性异常谱有重叠的疾病。最近报道这两种综合征均存在RAS-MAPK通路的突变，其中HRAS突变是CS的特征，而BRAF和MEK1/2突变是CFC的特征。我们报告一名3岁男孩，他在8个月大时因肥厚型心肌病接受了心脏移植；随后他被怀疑患有CS。在35个月大时，他出现了心脏内肿块，被诊断为转移性肝母细胞瘤。尽管肝母细胞瘤在免疫功能低下患者中的发生率并未升高，但有人提出移植后免疫抑制治疗是否在肿瘤发生中起作用的问题。该患者此后不久死亡，其尸检DNA分析显示存在先前在CFC中报道的MEK1突变（Y130C）。虽然CS与癌症风险增加有关，但在CFC患者中仅报道过1例白血病病例，因此这是CFC患者中报道的首例实体瘤病例。
