MYH11延长突变导致巨膀胱-小结肠-肠蠕动不良综合征1例报告及文献复习

doi:10.12372/jcp.2024.24e0263

摘要/Abstract

摘要：

目的报告1例MYH11基因杂合新发突变导致巨膀胱-小结肠-肠蠕动不良综合征（MMIHS）患儿的临床表现与遗传信息，并通过文献回顾性分析进行基因型-表型关联研究。方法分析2023年10月因“反复腹胀、呕吐3年余”来院就诊的MMIHS患儿临床资料，采集患儿及父母与姐姐的外周血样，通过Trio-WES及Sanger测序筛查致病突变。并对相关文献进行总结分析。结果患儿，男，15岁，主要临床表现为频繁发作的腹胀、呕吐和腹痛，腹部立位片及上消化道造影提示肠梗阻，给予灌肠、抗感染和静脉营养支持等治疗后病情稳定。基因检测结果显示，患儿携带MYH11基因杂合新发变异c.5819delC（p.Pro1940Hisfs*91），该变异导致肌球蛋白重链C端延长，父母及姐姐均未检测出该变异。文献检索共纳入7篇与MYH11基因变异有关文献，变异类型包括错义突变、移码突变和染色体微缺失。共20例，2例因提前终止妊娠性别不明，其余患者男女比2:1。基因型-表型关联分析发现，15例携带MYH11基因延长突变显性遗传患者的发病年龄9（0~28）岁，尚未报道死亡案例。5例携带双等位基因丧失功能突变的隐性遗传患者发病年龄均小于1岁，死亡4例（80 %）。结论本例MMIHS患儿携带MYH11基因c.5819delC（p.Pro1940Hisfs*91）变异。与携带MYH11基因变异隐性遗传的患者相比，MYH11延长突变显性遗传患者大部分发病较晚，临床表现较轻，生存率较高。

关键词: 巨膀胱-小结肠-肠蠕动不良综合征, MYH11基因, 儿童

Abstract:

Objective To report the clinical characteristics and genetic variant of a patient with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) and to investigate the genotypic-phenotypic correlation through literatures review. Methods The clinical data of a MMIHS child who came to our hospital in October 2023 due to "repeated abdominal distension and vomiting for more than 3 years" were analyzed. Peripheral blood samples were collected from the patient, his parents and his older sister, and the pathogenic mutation was screened by Trio-WES and Sanger sequencing. Relevant literature was summarized and analyzed. Results The patient, a 15-year-old boy, presented with recurrent episodes of abdominal distension, vomiting, and abdominal pain. Abdominal X-ray and upper gastrointestinal contrast study indicated intestinal obstruction. The condition stabilized after treatment with enema, anti-infection and intravenous nutritional support. Genetic testing revealed a heterozygous mutation in the MYH11 gene, identified as c.5819delC (p.Pro1940Hisfs*91), which resulted in the extension of the C-end of the myosin heavy chain and was not detected by either parent or sister. A total of 7 articles related to MYH11 gene mutation were included in the literature review. Mutation types included missense mutations, frameshift mutations, and chromosomal microdeletion. Gender was undetermined in 2 out of 20 patients due to early termination of pregnancy. Among the remaining patients, the male-to-female ratio was 2:1. Genotypic-phenotypic correlation analysis found that 15 patients with dominant heterozygous protein‐elongating MYH11 variants were aged 9 (0-28) years at onset, and no deaths were reported. Five patients with recessive loss-of-function mutations had an onset age of less than 1 year, with 4 deaths (80%). Conclusion This MMIHS patient carries the MYH11 gene c.5819delC (p. Pro1940Hisfs*91) mutation. Compared with patients with MYH11 gene mutation recessive inheritance, those with dominant MYH11 mutations tend to have a later onset, milder clinical manifestations, and a higher survival rate.

Key words: megacystis-microcolon-intestinal hypoperistalsis syndrome, MYH11 gene, child

周洁, 刘克强, 王金玲, 王莹. MYH11延长突变导致巨膀胱-小结肠-肠蠕动不良综合征1例报告及文献复习[J]. 临床儿科杂志, 2024, 42(9): 798-804.

ZHOU Jie, LIU Keqiang, WANG Jinling, WANG Ying. Megacystis-microcolon-intestinal hypoperistalsis syndrome caused by MYH11 elongating mutation : a case report and literatures review[J]. Journal of Clinical Pediatrics, 2024, 42(9): 798-804.

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病例	性别	发病年龄	消化系统症状	泌尿系统症状	其他	结局	文献
1	男	0	小结肠、便秘	巨膀胱、尿潴留	羊水少	死亡	[16]
2	男	0	小结肠	巨膀胱、肾盂扩张、输尿管扩张	瞳孔扩大、羊水少、感音神经性听力损失、肺动脉高压、主动脉扩张	死亡	[15]
3-1	－	0	－	巨膀胱	羊水少	终止妊娠	[13]
3-2	－	0	－	巨膀胱	羊水少	终止妊娠	[13]
4	女	0	小结肠	巨膀胱	生长激素缺乏、甲状腺功能减退、瞳孔扩大	存活	[14]
5	女	0	假性肠梗阻、回肠扭转、肛门括约肌张力低下	－	－	存活	[11]
6-1	男	11岁	食管裂孔疝	－	－	存活	[11]
6-2	男	7岁	食管裂孔疝、食道狭窄	－	－	存活
6-3	男	12岁	食管裂孔疝、食道狭窄	－	－	存活
6-4	女	4岁	食管裂孔疝、结肠动力障碍、十二指肠扩张	－	－	存活
6-5	女	4岁	食管裂孔疝、食道狭窄、十二指肠、空肠动力异常、坏死性小肠结肠炎	－	－	存活
7	男	12岁	假性肠梗阻	肾积水、尿路感染	－	存活	本文

病例	DNA	蛋白	突变类型	遗传方式	文献
1	c.3598A>T	p.Lys1200Ter	纯合错义突变	AR	[16]
2	c.2809_2810del；c.3422_3470del	p.Arg937Glyfs7；p.Lys1141Thrfs20	复合杂合突变	AR	[15]
3	c.2051G>A；c.3540_3541delinsTT	p.R684H ；p.（E1180D, Q1181Ter）	复合杂合突变	AR	[13]
4	c.379C>T；16p13.11 中1.3 Mb微缺失	p.Pro127Ser	复合杂合突变	AR	[14]
5	c.5819delC	p.Pro1940Hisfs*91	杂合延长突变	AD	[11]
6	c.5819_5820insCA	p.Gln1941Asnfs*91	杂合延长突变	AD	[11]
7	c.5819delC	p.Pro1940Hisfs*91	杂合延长突变	AD	本文
8	c.5819delC	p.Pro1940HisfsTer91	杂合延长突变	AD	[12]
9	c.5819delC	p.Pro1940Hisfs*91	杂合延长突变	AD	[6]