Objective: To analyze clinical, immunological and genetic characteristics of 4 cases of LIG4 syndrome. Methods: We retrospectively analyzed the clinical data of 4 patients from 3 families with LIG4 syndrome who were admitted to Children's Hospital of the Capital Institute of Pediatrics from June 2017 to May 2018, and reviewed related articles, the clinical, immunological and genetic characteristics of LIG4 syndrome were summarized and analyzed. Results: Those 4 cases (P1 to P4), including 2 males and 2 females, had an average age of 1.5 years. All of them presented with special facial features, such as microcephaly, beak-like-nose, and receding forehead. Three of them presented with delayed physical development. P3 suffered from mental retardation and P4 had feeding difficulty. BCG scars were repeatedly ruptured in 3 cases, 4 cases had pneumonia, 1 case had EB virus infection, 2 cases had cytomegalovirus infection, 1 case had fungal infection, and 1 case had chronic diarrhea. Blood routine tests showed decreased neutrophil and lymphocyte counts. Immunoassay showed decreased absolute count of CD4(+)T lymphocyte and B lymphocyte, with normal CD8(+)T cells. P1, P2 presented with decreased immunoglobulin. All of those patients had LIG4 gene complex heterozygous mutations, of whom one had missense mutation had mild clinical phenotype and another three cases had frameshift mutation presented with severe clinical phenotype. One patient underwent hematopoietic stem cell transplantation, and has established normal immune function. He did not have recurrent infection during one year follow-up period. The other 3 patients had preventive anti-infection treatment and received regular human immunoglobulin infusion, but they still had recurrent infection. In literature review, 67 articles were retrieved, totally 37 case were reported, showing special faces and recurrent infection as characteristic presentation of this disease. Conclusions: The typical manifestations of LIG4 syndrome are microcephaly, special facial features and repeated infection. The average age at diagnosis of LIG4 syndrome was more than one year old. If a patient presented with microcephaly, BCG scar infection and leukopenia, LIG4 syndrome should be considered. Immunoglobulin is decreased at different degrees, and CD4(+) and CD19(+) lymphocyte counts always decrease, Naive T and B cells decrease more prominently, and CD8(+)T cells were normal in patients with typical LIG4 syndrome. It is effective to reconstruction of immune system with bone marrow transplantation in LIG4 syndrome patients.
目的： 分析LIG4综合征的临床、免疫学和遗传学特点。 方法： 回顾性分析首都儿科研究所附属儿童医院风湿免疫科2017年6月至2018年5月收治的3个家系中的4例LIG4综合征患儿临床资料，并以"LIG4综合征""小头畸形"等作为关键词，对PubMed建库到2019年1月的文献进行检索，结合文献复习，对LIG4综合征的临床、免疫学和遗传学特点进行总结分析。 结果： 共4例（例1~例4）患儿中男2例、女2例，平均确诊年龄1岁6月龄。均有小头畸形、鼻大、额头窄特殊面容，3例有体格发育落后，例3有智力、运动落后，例3有喂养困难。卡介苗疤痕反复破溃3例，肺炎4例，EB病毒感染1例、巨细胞病毒感染2例，真菌感染1例，慢性腹泻1例。4例患儿血常规显示中性粒细胞及淋巴细胞计数减低，免疫分析CD4(+)T淋巴细胞及B淋巴细胞绝对计数降低，CD8(+)T细胞绝对计数正常；例1、例2免疫球蛋白降低。4例患儿均为LIG4基因复合杂合变异。1例行半相合造血干细胞移植，建立正常免疫功能，随访近1年未发生反复感染；另外3例预防性抗感染，定期人免疫球蛋白输注，仍反复感染。文献报道：检索国内外文章67篇，共37例报道，表现为特殊面容及反复感染。 结论： LIG4综合征典型表现为小头畸形、特殊面容、反复感染、卡介苗疤痕破溃、白细胞降低；该病免疫球蛋白多有不同程度降低，CD4(+)、CD19(+)淋巴细胞计数降低，Naive细胞减少更为突出，CD8(+)T细胞正常；平均确诊年龄1岁余。4例均为LIG4基因复合杂合变异。骨髓移植对该病免疫重建有效。.
Keywords: Infection; LIG4 syndrome; Microcephaly.