中国循证儿科杂志2025，Vol.20Issue(4)：241-247,7.DOI:10.3969/j.issn.1673-5501.2025.04.001
Phelan-McDermid综合征患儿基因型-神经发育特征表型的回顾性队列研究
Correlation between genotype and neurodevelopmental features in patients with Phelan-McDermid syndrome:A retrospective cohort study
摘要
Abstract
Background Phelan-McDermid syndro me(PMS)is caused by deletion of 22q13.3(typically including heterozy-gous deletion of the SHANK3 gene)or pathogenic variants in the SHANK3 gene.It is a rare developmental disorder characterized by prominent global developmental delay/intellectual disability,severe language developmental delay,and autism spectrum disor-der(ASD)features.Most studies on the clinical phenotype of PMS relied on parental reports or questionnaires,which had exten-sive heterogeneity,and there were few studies that directly evaluate patients through standardized assessment tools by professionals to study the genotype-neurodevelopmental phenotype.Objective To investigate the association between neurodevelopmental fea-tures and the size of the 22q13.3 deletion in PMS.Design Retrospective cohort study.Methods Patients were admitted to the de-partment of pediatric health at Children's Hospital of Fudan University from January 2014 to December 2022.Patients diagnosed with PMS and confirmed through CNV verification of the size of the 22q13.3 deletion fragment,MLPA or Sanger verification of the SHANK3 gene defect types,and who completed assessments using the Griffiths Mental Developmental Scales-Chinese version(Griffiths),Autism Diagnostic Observation Schedule-2nd Edition(ADOS-2),and VINELAND adaptive behavior scales-chinese version,were included in this study.Patients were further divided into two groups based on the size of the deletion fragments:Group I,consisting of patients with pathogenic variants in the SHANK3 gene(partial exons deletion or pathogenic point muta-tions),and Group Ⅱ,consisting of patients with a 22q13.3 deletion that includes a heterozygous deletion of the entire SHANK3 gene.The developmental level,severity of autism,and adaptive abilities were analyzed.Age group was divided into≤6 years old group and>6 years old group for the analysis of developmental differences.Main outcome measures The correlation between genotype and neurodevelop mental features.Results A total of 39 patients were included in the analysis(20 males and 19 fe-males),with an average age of 52.7±21.9 months.There were no statistically significant differences between Group Ⅰ and Group Ⅱ regarding testing age and gender.In terms of developmental level,Griffiths showed that Group Ⅰ had higher average developmental quotient(DQ)scores than Group Ⅱ in the areas of gross motor,personal-social,language,hand-eye coordination and perfor-mance,but the differences were not statistically significant.When divided by age group,the≤6 years old group had significantly higher developmental levels in gross motor skills,hand-eye coordination,and performance compared to the>6 years old group.Re-garding autism severity,there was no significant difference between the two groups based on ADOS-2 severity scores.In terms of adaptive abilities,VINELAND showed that Group Ⅰ had higher average standard scores than Group Ⅱ in all four domains and the overall scale,but only the overall scale standard score of Group Ⅰ was significantly higher than that of Group Ⅱ,with a statistically significant difference.Further analysis of DQ values in each subdomain showed that Group Ⅰ had higher average DQ scores than Group Ⅱ.However,statistically significant differences were only found in the expressive subdomain,personal subdomain,daily liv-ing skills domain,gross motor subdomain,motor skills and overall scale.Conclusion SHANK3 gene defects alone are sufficient to produce the neurobehavioral phenotypes of PMS.Patients with SHANK3 gene defects have significantly higher adaptive levels in two major domains(daily living skills and motor skills)and three subdomains(expressive language,personal,gross motor)as well as the overall scale compared to patients with 22q13.3 deletions alone.However,there were no significant differences in develop-mental levels or autism symptom severity between patients with SHANK3 gene defects and those with 22q13.3 deletions alone.Pre-school patients exhibited higher developmental levels than school-age patients,suggesting the importance of early evaluation,early intervention,regular comprehensive assessments to monitor children's developmental progress.关键词
Phelan-McDermid综合征/SHANK3基因/发育/孤独症/适应性能力Key words
Phelan-McDermid syndrome/SHANK3 gene/Development/Autism/Adaptive abilities引用本文复制引用
刘春雪,邓晶鑫,徐秀,李慧萍,张凯峰,董萍,徐琼,周秉睿,胡纯纯,张颖,王怡..Phelan-McDermid综合征患儿基因型-神经发育特征表型的回顾性队列研究[J].中国循证儿科杂志,2025,20(4):241-247,7.基金项目
国家自然科学基金面上项目:82171540 （）
国家自然科学基金青年项目:82101945 （）
