儿童Bainbridge-Ropers综合征1例
1. 宁波大学, 医学部, 浙江宁波 315211
2. 宁波大学附属妇女儿童医院, 儿科, 浙江宁波 315012
| 摘 要： | Bainbridge-Ropers综合征（Bainbridge-Ropers syndrome，BRPS）是额外性梳样蛋白3（additional sex combs-like 3, ASXL3）基因功能缺失变异诱发的罕见常染色体显性遗传多系统发育疾病，全球病例报道较少，婴儿期临床表现缺乏特异性，极易发生漏诊、误诊。本文报道1例儿童BRPS的临床诊疗过程，并结合基因检测结果、病理特征分析探讨该病的临床特征、诊断要点及诊疗策略。男性患儿，5月8天，因“喂养困难5月，加重3天”而收治入院。自新生儿期即存在吃奶停顿、频繁呛咳，奶量摄入长期不足，体格检查示体重增长缓慢、生长发育落后于同龄儿；完善相关检查后，可排除感染、消化道解剖畸形、牛奶蛋白过敏及常见代谢缺陷类疾病，经全外显子组高通量测序检测发现患儿ASXL3基因c.3380_3381insT（p.R1128Pfs*22）杂合变异，结合其临床表型及影像表现符合BRPS诊断标准。目前患儿于家中鼻饲喂养中，但喂养过程中患儿呕吐、反流仍较明显，反应欠佳。本研究通过分析该病例的临床特征与基因检测结果，结合相关文献系统回顾，旨在提高临床医师对该疾病的认知水平及早期诊断能力，推动疑似发育迟缓伴顽固性喂养困难患儿尽早开展基因检测，实现该疾病的早期识别与长期规范化对症干预。 |
| 关 键 词： | Bainbridge-Ropers综合征; 儿童; ASXL3基因; 基因诊断; 发育迟缓 |
| DOI： | 10.57237/j.wjcm.2026.02.002 |
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收稿日期: 2026-06-22
接受日期: 2026-07-21
在线出版日期: 2026-08-05
A Case of Bainbridge-Ropers Syndrome in a Child
1. Health Science Center, Ningbo University, Ningbo 315211, China
2. Department of Pediatrics, Women and Children’s Hospital of Ningbo University, Ningbo 315012, China
| Abstract: | Bainbridge-Ropers syndrome (BRPS) is a rare autosomal dominant multisystem developmental disorder caused by loss-of-function variants in the additional sex combs-like 3 (ASXL3) gene. With few cases reported worldwide, its clinical manifestations during infancy lack specificity, rendering it highly susceptible to missed diagnosis and misdiagnosis.This paper reports the clinical diagnosis and treatment process of a child with BRPS. Through integration of genetic testing results, pathological characteristics analysis, and a literature review, this article discusses explore the clinical features, diagnostic key points, and management strategies of this disease. The patient is a 5-month-and-8-day-old male infant, admitted with the chief complaint of "feeding difficulty for 5 months, aggravated in the past 3 days." He presented with pauses during feeding and frequent choking since the neonatal period, accompanied by chronically inadequate milk intake. Physical examination revealed slow weight gain and developmental delay compared with age-matched peers. After completing relevant examinations, infectious diseases, anatomical gastrointestinal malformations, cow’s milk protein allergy and common metabolic disorders were excluded. Whole-exome high-throughput sequencing identified a heterozygous variant c.3380_3381insT (p.R1128Pfs*22) in the additional sex combs-like 3 (ASXL3) gene. Combined with the clinical phenotype and imaging manifestations, the findings met the diagnostic criteria for BRPS. Currently, the infant is receiving nasogastric tube feeding at home, but vomiting and reflux remain significant during feeding, with poor responsiveness. By analyzing the clinical characteristics and genetic test results of this case along with a systematic literature review, this study aims to enhance clinicians' understanding of the disease and improve early diagnostic ability, facilitate timely genetic testing in children suspected of developmental delay with intractable feeding difficulties, and support early recognition of BRPS as well as long-term standardized symptomatic intervention. |
| Keywords: | Bainbridge-Ropers Syndrome; Children; ASXL3 Gene; Genetic Diagnosis; Developmental Delay |
基金
| 1. | 宁波市公益科技计划项目 (No. 2023S097) |
参考文献
| [1] | 杨慧, 刘霞, 王琪. 儿童神经发育障碍性疾病临床检查与遗传因素分析 [J]. 脑与神经疾病杂志, 2025, 33(06): 341-345. |
| [2] | SCHIRWANI S, WOODS E, KOOLEN D A, et al. Familial Bainbridge-Ropers syndrome: Report of familial ASXL3 inheritance and a milder phenotype [J]. Am J Med Genet A, 2023, 191(1): 29-36. |
| [3] | DINWIDDIE D L, SODEN S E, SAUNDERS C J, et al. De novo frameshift mutation in ASXL3 in a patient with global developmental delay, microcephaly, and craniofacial anomalies [J]. BMC Med Genomics, 2013, 6: 32. |
| [4] | TRUJILLANO L, VALENZUELA I, COSTA-ROGER M, et al. Comprehensive Clinical and Genetic Characterization of a Spanish Cohort of 22 Patients With Bainbridge-Ropers Syndrome [J]. Clin Genet, 2025, 107(6): 646-662. |
| [5] | IKEKWERE J C, OSUAGWU F C, LEPLATTE D, et al. Comorbid Psychiatric Aspects of Bainbridge-Ropers Syndrome [J]. Prim Care Companion CNS Disord, 2021, 23(3): 20m02783. |
| [6] | SCHIRWANI S, ALBABA S, CARERE D A, et al. Expanding the phenotype of ASXL3-related syndrome: A comprehensive description of 45 unpublished individuals with inherited and de novo pathogenic variants in ASXL3 [J]. Am J Med Genet A, 2021, 185(11): 3446-3458. |
| [7] | WOODS E, HOLMES N, DENOMMé-PICHON A S, et al. An International ASXL3 Natural History Study: Deep Phenotypic Analyses Including Detailed Reports of a Milder Phenotype, Novel Associations, and Clinical Recommendations [J]. Am J Med Genet A, 2025, 197(11): e64157. |
| [8] | LOH C H, VEENSTRA G J C. The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development [J]. Epigenomes, 2022, 6(3): 23. |
| [9] | OSS-RONEN L, SARUSI T, COHEN I. Histone Mono-Ubiquitination in Transcriptional Regulation and Its Mark on Life: Emerging Roles in Tissue Development and Disease [J]. Cells, 2022, 11(15): 2404. |
| [10] | ZHAO B, DING F, HOU F, et al. Paternal mosaicism in ASXL3-related bainbridge-ropers syndrome: implications for genetic counseling and prenatal diagnosis [J]. Front Pediatr, 2025, 13: 1655021. |
| [11] | DAI B, YUAN Y, SHEN Y, et al. A novel ASXL3 gene variant in a Chinese Boy causing Bainbridge [J]. BMC Infect Dis, 2025, 25(1): 1409. |
| [12] | CUDDAPAH V A, DUBBS H A, ADANG L, et al. Understanding the phenotypic spectrum of ASXL-related disease: Ten cases and a review of the literature [J]. Am J Med Genet A, 2021, 185(6): 1700-1711. |
| [13] | AYOUB M C, ANDERSON J T, RUSSELL B E, et al. Examining the neurodevelopmental and motor phenotypes of Bohring-Opitz syndrome (ASXL1) and Bainbridge-Ropers syndrome (ASXL3) [J]. Front Neurosci, 2023, 17: 1244176. |
| [14] | YANG L, GUO B, ZHU W, et al. Bainbridge-ropers syndrome caused by loss-of-function variants in ASXL3: Clinical abnormalities, medical imaging features, and gene variation in infancy of case report [J]. BMC Pediatr, 2020, 20(1): 287. |
| [15] | KUECHLER A, CZESCHIK J C, GRAF E, et al. Bainbridge-Ropers syndrome caused by loss-of-function variants in ASXL3: a recognizable condition [J]. Eur J Hum Genet, 2017, 25(2): 183-191. |
