家族性腺瘤性息肉病一例临床特点及基因分析

Clinical and molecular characteristics of a child with familial adenomatous polyposis

目的探讨儿童早期发病的家族性腺瘤性息肉病（FAP）的临床及基因突变特点。方法回顾性分析2004年2月在北京大学第三医院确诊的l例FAP患儿的临床特点及11年随访期间内镜、病理表现，观察舒林酸的治疗效果，并采用PCR—DNA第一代测序法进行结肠腺瘤性息肉病（APC）基因突变分析。结果患儿女，6岁时因“间断大便带血1．5年”入院。结肠镜检查结肠和直肠可见数百枚息肉，病理结果示管状腺瘤Ⅱ～Ⅲ级。随访11年期间患儿临床表现为间歇黏液血便，内镜检查提示结直肠息肉逐渐增多至千枚，并出现胃底、胃体部多发息肉。13岁时加用舒林酸治疗后息肉数目及病理分级略有改善，息肉活检未发现癌变。尚未手术治疗。患儿基因检测提示APC基因15外显子1309位存在杂合缺失（c．3927_3931delAAAGA），其父母相应位点未见突变。父母肠镜未见多发息肉。结论此例FAP患儿发病早，随年龄增长病情进展，舒林酸治疗对控制息肉大小及数目有部分疗效；突变位点符合经典型FAP，但无家族史，可能为散发突变。

Objective To explore the clinical features and molecular mutation of early-onset familial adenomatous polyposis（FAP） in childhood. Method The clinical features, endoscopic findings, pathology and therapeutic effect of sulindac during 11 years follow-up in a child with FAP were retrospectively reviewed . Adenomatous polyposis coli （APC） gene mutation analysis was performed by PCR and first generation sequencing. Result This 6-year-old girl was admitted for intermittent bloody stool during the last one and a half years. Colonoscopy showed hundreds of polyps in the rectum and colon. Pathological examination revealed tubular adenomas with high grade dysplasia. During the follow-up period of 11 years, the child presented intermittent mucous bloody stool. Endoscopy showed the number of polyps in colon and rectum increased to thousands, and found multiple polyps in gastric fundus and body. She was treated with sulindac at the age of 13. Then the number of polyps and the grade of pathology showed a slight improvement and no carcinoma was seen on biopsy. She has not accepted surgery until now. Gene sequencing of this child revealed 5 bp deletion at codon 1 309 of exon 15 （c. 3927 3931delAAAGA） of tumor suppressor gene, whereas none of her parents had the same mutation. And no polyps were found on her parents colonoscopy. Conclusion This child with FAP had an early onset of this disease, and clinical conditions were exacerbated with age. Sulindac was partially effective in controlling size and number of polyps. The site of mutation in this case was consistent with classic FAP, and without family history, the mutation may be a sporadic one.