Clinical diagnosis and literature review of Helsmoortel-Van der Aa syndrome
LI Yu, CHEN Qihui, WU Ruohao, SUN Yi, TANG Danxia, LI Dongfang, HE Zhanwen.
Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Department of Pediatric Neurology, Guangzhou 510120, China
引用本文:
李宇,陈启慧,吴若豪,等. Helsmoortel-Van der Aa综合征的临床诊断和文献复习[J]. 温州医科大学学报, 2023, 53(10): 834-838.
Cite this article:
LI Yu,CHEN Qihui,WU Ruohao, et al. Clinical diagnosis and literature review of Helsmoortel-Van der Aa syndrome[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(10): 834-838.
摘要目的：总结1例由ADNP基因变异所致的Helsmoortel-Van der Aa综合征（HVDAS）的临床表现及遗传学特点，并进行国内外相关文献复习。方法：对2020 年8月于中山大学孙逸仙纪念医院儿科神经专科确诊的1例HVDAS患儿的临床表现、生化检查及基因检测等临床资料进行回顾性分析。同时检索国内外数据库中有关ADNP基因变异所致的HVDAS患儿的文献。结果：本例患儿，男，5岁10个月，因“运动、语言发育迟缓5年余，社交障碍2年余”入院。患儿表现为智力障碍、孤独症谱系、发育迟缓、特殊面容、睾丸鞘膜积液、隐睾及睾丸微石症等。基因检测发现该患儿携带一个ADNP杂合致病突变，即ADNP（NM_015339.3）Exon3：c.56_57delTG：p.（Val19fs）基因突变，父母均未发现该基因突变。文献检索到102例患儿（包含本例患儿），平均年龄6.3岁，男女比例为3:2。相关文献报道所有患儿都有轻到重度智力障碍、严重的语言和运动发育迟缓。孤独症谱系障碍、特征性的面部外观也很常见。结论：HVDAS是一种罕见常染色体显性的神经发育障碍性疾病，临床上对于发育迟缓、孤独症谱系障碍、特殊面容的患儿，应考虑到HVDAS的可能性，应及早进行基因检测，基因检测发现ADNP基因变异可明确诊断。
Abstract：Objective: To summarize the clinical manifestations and genetic characteristics of Helsmoortel-Van der Aa syndrome (HVDAS) caused by ADNP gene mutation with a review of the related literatures. Methods:The clinical data of the patient with HVDAS confirmed in August 2020 at the Department of Pediatrics of Sun Yat-sen Memorial Hospital, Sun Yat-sen University were collected retrospectively. The data for analysis included clinical manifestations, biochemical tests and gene tests. Meanwhile, literatures on HVDAS caused by ADNP gene mutation were searched from domestic and foreign databases. Results: The patient, male, 5 years and 10
months old, was admitted to hospital due to motor and language development retarding for more than 5 years and social communication impairment for more than 2 years. The children presented with intellectual disability,autism spectrum, developmental delay, special facial features, hydrocele of testis, cryptorchidism and testicular microlithiasis. Genetic examination report shows that the child carries a heterozygous pathological mutation of ADNP gene: ADNP (NM_015333.9) Exon3: c.56_57delTG: p.(Val19fs), which is not found in either parent.And this gene mutation site has not been reported. A total of 102 children (including this case) were found in the literature, with an average age of 6.3 years and a male to female ratio being 3:2. All children were reported to have mild to severe intellectual impairment and severe language and motor retardation. Autism spectrum disorders and characteristic facial appearance are also common. Conclusion: HVDAS is a rare autosomal dominant neurodevelopment disorder. The possibility of HVDAS should be clinically considered in children with developmental retardation, autism spectrum disorder and specific features. Gene sequencing should be performed as early as possible, and the detection of ADNP gene variation in genetic testing can make a clear diagnosis.
