Igarashi Takehito, Okamura Ritsuko, Jikuzono Tomoo, Uchino Shinya, Sugitani Iwao, Shimizu Kazuo
Division of Endocrine Surgery, Department of Surgery, Nippon Medical School.
J Nippon Med Sch. 2014;81(2):64-9. doi: 10.1272/jnms.81.64.
Familial medullary thyroid carcinoma (FMTC) is an autosomal dominant inherited disease that has highly characteristic clinical features, including medullary thyroid carcinoma (MTC). Mutation of the RET proto-oncogene is known to be responsible for development of FMTC and for multiple endocrine neoplasia types 2A and 2B. Hirschsprung's disease is the most common form of structural intestinal obstructive disease in human newborns. Hirschsprung's disease is defined by the absence of neural crest-derived enteric ganglia along a variable length of the bowel that invariably involves the rectoanal junction. Co-segregation of FMTC and Hirschsprung's disease is uncommon; nevertheless, in 3 generations of 1 family, we observed 5 patients with FMTC, 2 patients with Hirschsprung's disease, and 1 patient with characteristics of both FMTC and Hirschsprung's disease. Moreover, a Cys620Ser mutation in RET was identified in 4 of the 8 patients. This mutation had both activating and inactivating effects on the RET (REarranged during Transfection) protein. There were individual differences in the penetrance of Hirschsprung's disease due to the RET mutation, but the penetrance of MTC was uniform and high. Genetic testing is important for making decisions about treatment and follow-up in families of this kind.
家族性甲状腺髓样癌（FMTC）是一种常染色体显性遗传病，具有高度特征性的临床特征，包括甲状腺髓样癌（MTC）。已知RET原癌基因的突变是FMTC以及2A和2B型多发性内分泌肿瘤发生的原因。先天性巨结肠是人类新生儿中最常见的结构性肠梗阻疾病形式。先天性巨结肠的定义是沿肠管可变长度缺乏神经嵴衍生的肠神经节，且总是累及直肠肛管连接部。FMTC与先天性巨结肠的共分离并不常见；然而，在一个家族的3代人中，我们观察到5例FMTC患者、2例先天性巨结肠患者以及1例同时具有FMTC和先天性巨结肠特征的患者。此外，在8例患者中的4例中鉴定出RET基因的Cys620Ser突变。该突变对RET（转染期间重排）蛋白具有激活和失活作用。由于RET突变，先天性巨结肠的外显率存在个体差异，但MTC的外显率一致且很高。基因检测对于此类家族的治疗和随访决策很重要。
