Genetic analysis of a case of ring chromosome 18 child and literature review

doi:10.3969/j.issn.1673-8640.2025.02.006

Abstract

Abstract:

Objective To conduct a genetic analysis on a child with mental decline and delayed growth and development，and to analyze the relationship between clinical phenotype and genetic characteristics. Methods The clinical data from the patient with mental decline and delayed growth and development were collected. G-banding karyotype analysis and copy number variation sequencing（CNV-seq） were performed. Using "ring chromosome 18" as the keyword，the papers included in China National Knowledge Infrastructure，Wanfang Data Knowledge Service Platform and PubMed were searched from January 1998 to October 2024. The clinical manifestations and chromosomal karyotype analysis results of patients with ring chromosome 18 were summarized. Results The child had a distinctive facial appearance，and the chromosomal karyotype analysis result was 46，XY，r（18）（p11.21q23）. The CNV-seq result was seq[hg19]del（18）（p11.32p11.21）chr18：g.120000_14980000del，indicating a 14.86 Mb copy number deletion in the 18p11.32p11.21 region，diagnosed with ring chromosome 18. The chromosomal karyotypes of the child's parents were both normal. A total of 16 papers on ring chromosome 18 were searched（16 cases）. Among the 17 patients，distinctive facial appearance accounted for 100.00%（17/17），mental decline accounted for 93.75%（15/16，excluding one prenatally diagnosed fetus），language and behavioral delays accounted for 64.71%（11/17），short stature accounted for 52.94%（9/17），neurodevelopmental abnormalities accounted for 41.18%（7/17），microcephaly accounted for 17.65%（3/17），cardiac anomalies accounted for 23.53%（4/17），endocrine and immune system abnormalities accounted for 17.65%（3/17），hypotonia accounted for 17.65%（3/17），ocular abnormalities accounted for 17.65%（3/17），epilepsy accounted for 11.76%（2/17），gonadal dysgenesis accounted for 11.76%（2/17），and skin lesions accounted for 5.88%（1/17）. Conclusions Children with ring chromosome 18 may present with manifestations such as delayed growth and development，mental decline，distinctive facial appearance，neurodevelopmental abnormalities and cardiac anomalies. Their clinical phenotypes are related to the location of the chromosome deletion and the size of the deleted segment.

Key words: Ring chromosome 18, Chromosomal karyotype analysis, Copy number variation sequencing

CLC Number:

R446.1

HUANG Bingyi, ZHAO Qin, YU Donglan, WANG Manyi, ZHU Chunjiang. Genetic analysis of a case of ring chromosome 18 child and literature review[J]. Laboratory Medicine, 2025, 40(2): 135-141.

Figures/Tables 5

References 37

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病例序号	性别	年龄/岁	染色体核型	缺失区域	缺失长度	缺失基因	参考文献
1^①	男	7.0	46，XY，r（18）（p11.21q23）	18p11.32p11.21	14.86 Mb	TGIF1	本例
2	女	3.0	46，XX，r（18）（p11.32q22.2）	18q	9.775 Mb		[4]
3	男	20.0	46，XY，r（18）	18q12.1	442 Kb	DTNA	[5]
4	男	2.5	46，XY，r（18）（p11.32q21.32）	18q21.31 18q21.33			[6]
5	女	1.0	46，XY，r（18）（p11.31q21.31）	18p11.32p11.31 18q21.31q23	6.3 Mb、21.9 Mb	MBP、TGIF1、TSHZ1	[7]
6	女	12.0	46，XY，r（18）				[8]
7	女	22.0	46，XY，r（18）（p11.3q23）[24]/46，XX[36]				[9]
8	男	6.0	46，XY，r（18）（p11q23）				[10]
9	女	4.0	46，XY，r（18）[31]/46，XY，r（18；18）[8]/45，XX，-18[10]				[11]
10	女	8.0	46，XX，18，+18（p11p23）				[12]
11	男	1.6	46，XY，r（18）（p11.3q23）	18p11.32p11.21 18q23	8.8 Mb、918 Kb		[13]
12	男	0.6	46，XY，-18，+r（18q）18p-18q-				[14]
13	女	11.7	46，XX，r（18）（p11.3q23）[70]/46，XX，der（18）r（18）（p11.3q23；p11.3q23）[14]/45，XX，-18[6]	18q22.3q23	7.779 Mb		[15]
14	女	1.9	46，XY，r（18）（p11.32q22.1）	18p11.32 18q22.1q23	360 Kb、14.77 Mb		[16]
15^②	男		46，XY，r（18）（p11.3q21.3）	18p11.32p11.31 18q21.33q23	3.3 Mb、16.9 Mb	TGIF1、TWSG、TYMS、USP14	[17]
16	女	6.0	46，XX，r（18）（p11.31q23）	18p11.31 18q23	3.88 Mb、4.83 Mb	USP14、TGIF1、GALR1、CTDP1	[18]
17	男	3.9	46，XY，r（18）（p11.21q22.1）[40]/46，XY[7]	18p11.21p11.32 18q22.1q23	14.86 Mb、14.02 Mb	TGIF1	[19]

病例序号	性别	年龄/岁	染色体核型	缺失区域	缺失长度	缺失基因	参考文献
1^①	男	7.0	46，XY，r（18）（p11.21q23）	18p11.32p11.21	14.86 Mb	TGIF1	本例
2	女	3.0	46，XX，r（18）（p11.32q22.2）	18q	9.775 Mb		[4]
3	男	20.0	46，XY，r（18）	18q12.1	442 Kb	DTNA	[5]
4	男	2.5	46，XY，r（18）（p11.32q21.32）	18q21.31 18q21.33			[6]
5	女	1.0	46，XY，r（18）（p11.31q21.31）	18p11.32p11.31 18q21.31q23	6.3 Mb、21.9 Mb	MBP、TGIF1、TSHZ1	[7]
6	女	12.0	46，XY，r（18）				[8]
7	女	22.0	46，XY，r（18）（p11.3q23）[24]/46，XX[36]				[9]
8	男	6.0	46，XY，r（18）（p11q23）				[10]
9	女	4.0	46，XY，r（18）[31]/46，XY，r（18；18）[8]/45，XX，-18[10]				[11]
10	女	8.0	46，XX，18，+18（p11p23）				[12]
11	男	1.6	46，XY，r（18）（p11.3q23）	18p11.32p11.21 18q23	8.8 Mb、918 Kb		[13]
12	男	0.6	46，XY，-18，+r（18q）18p-18q-				[14]
13	女	11.7	46，XX，r（18）（p11.3q23）[70]/46，XX，der（18）r（18）（p11.3q23；p11.3q23）[14]/45，XX，-18[6]	18q22.3q23	7.779 Mb		[15]
14	女	1.9	46，XY，r（18）（p11.32q22.1）	18p11.32 18q22.1q23	360 Kb、14.77 Mb		[16]
15^②	男		46，XY，r（18）（p11.3q21.3）	18p11.32p11.31 18q21.33q23	3.3 Mb、16.9 Mb	TGIF1、TWSG、TYMS、USP14	[17]
16	女	6.0	46，XX，r（18）（p11.31q23）	18p11.31 18q23	3.88 Mb、4.83 Mb	USP14、TGIF1、GALR1、CTDP1	[18]
17	男	3.9	46，XY，r（18）（p11.21q22.1）[40]/46，XY[7]	18p11.21p11.32 18q22.1q23	14.86 Mb、14.02 Mb	TGIF1	[19]

病例序号	智力低下	特殊面容	语言与行为落后	身材矮小	小头畸形	心脏异常	神经发育异常	肌张力低下	内分泌与免疫系统异常	癫痫	性腺发育异常	眼部异常	皮肤病变	参考文献
1^①	+	+	+	+	+	-	-	-	-	-	-	-	-
2	+	+	+	+	-	-	+	+	-	-	-	+	-	[4]
3	+	+	-	-	+	+	-	-	-	-	-	-	-	[5]
病例序号	智力低下	特殊面容	语言与行为落后	身材矮小	小头畸形	心脏异常	神经发育异常	肌张力低下	内分泌与免疫系统异常	癫痫	性腺发育异常	眼部异常	皮肤病变	参考文献
4	+	+	-	-	-	-	-	-	-	-	+	-	-	[6]
5	+	+	+	+	+	+	-	-	-	+	-	+	+	[7]
6	+	+	+	+	-	-	+	+	+	+	-	-	-	[8]
7	+	+	+	+	-	+	+	-	-	-	+	-	-	[9]
8	+	+	+	-	-	+		-	-	-	-	-	-	[10]
9	+	+	+	-	-	-	-	-	-	-	-	-	-	[11]
10	+	+	-	-	-	-	-	-	-	-	-	-	-	[12]
11	+	+	+	+	-	-	-	-	-	-	-	-	-	[13]
12	+	+	+	+	-	-	+	-	-	-	-	-	-	[14]
13	+	+	-	+	-	-	-	-	+	-	-	-	-	[15]
14	+	+	+	-	-		+	-	-	-	-	-	-	[16]
15	-	+	-	-	-	-		-	-	-	-	-	-	[17]
16	+	+	-	+	-	-	+	-	+	-	-	+	-	[18]
17	+	+	+	-	-	-	+	+	-	-	-	-	-	[19]

病例序号	智力低下	特殊面容	语言与行为落后	身材矮小	小头畸形	心脏异常	神经发育异常	肌张力低下	内分泌与免疫系统异常	癫痫	性腺发育异常	眼部异常	皮肤病变	参考文献
1^①	+	+	+	+	+	-	-	-	-	-	-	-	-
2	+	+	+	+	-	-	+	+	-	-	-	+	-	[4]
3	+	+	-	-	+	+	-	-	-	-	-	-	-	[5]
病例序号	智力低下	特殊面容	语言与行为落后	身材矮小	小头畸形	心脏异常	神经发育异常	肌张力低下	内分泌与免疫系统异常	癫痫	性腺发育异常	眼部异常	皮肤病变	参考文献
4	+	+	-	-	-	-	-	-	-	-	+	-	-	[6]
5	+	+	+	+	+	+	-	-	-	+	-	+	+	[7]
6	+	+	+	+	-	-	+	+	+	+	-	-	-	[8]
7	+	+	+	+	-	+	+	-	-	-	+	-	-	[9]
8	+	+	+	-	-	+		-	-	-	-	-	-	[10]
9	+	+	+	-	-	-	-	-	-	-	-	-	-	[11]
10	+	+	-	-	-	-	-	-	-	-	-	-	-	[12]
11	+	+	+	+	-	-	-	-	-	-	-	-	-	[13]
12	+	+	+	+	-	-	+	-	-	-	-	-	-	[14]
13	+	+	-	+	-	-	-	-	+	-	-	-	-	[15]
14	+	+	+	-	-		+	-	-	-	-	-	-	[16]
15	-	+	-	-	-	-		-	-	-	-	-	-	[17]
16	+	+	-	+	-	-	+	-	+	-	-	+	-	[18]
17	+	+	+	-	-	-	+	+	-	-	-	-	-	[19]