Verbesselt Jente, Breckpot Jeroen, Zink Inge, Swillen Ann
Department of Human Genetics, Catholic University Leuven, Leuven, Belgium.
Research Group Experimental Oto-Rhino-Laryngology (ExpORL), Department of Neurosciences, Leuven Brain Institute, Catholic University Leuven, Leuven, Belgium.
J Neurodev Disord. 2025 Jun 19;17(1):33. doi: 10.1186/s11689-025-09615-7.
16p11.2 deletion syndrome (16p11.2DS) is a recurrent CNV that occurs de novo in approximately 70% of cases and confers risk for neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorders (ASD). The current study focusses on developmental milestones, cognitive profiles and longitudinal cognitive trajectories.
In-person assessments, digital medical records and parental interviews on developmental history of 24 children (5-16 years) with a confirmed BP4-BP5 16p11.2DS were reviewed and analysed for developmental milestones (motor, language, continence). Standardised intelligence tests were administered in all children, and longitudinal IQ-data were available for a subgroup (79%, 19/24).
Motor, language, and continence milestones were delayed. Average IQ was in the borderline range (IQ 71) with 46% (11/24) having borderline IQ (IQ 70-84). Both intra- and interindividual variability were found across the five cognitive domains with significant discrepancies between verbal and non-verbal skills in 55% (11/20). Longitudinal IQ-data indicate that school-aged children with 16p11.2DS perform statistically significantly lower at the second time point (p < 0.001) with 58% showing a growing into deficit trajectory.
Delayed motor, language and continence milestones are common in 16p11.2DS carriers. School-aged children with 16p11.2DS show increasing cognitive impairments over time, pointing to the need for early diagnosis, regular cognitive follow-up and individualised intervention. The high prevalence of disharmonic IQ-profiles highlights the importance of expanding the focus beyond full-scale IQ (FSIQ) outcomes. Future studies in larger cohorts including carrier relatives are needed to gain more insight into the penetrance and phenotypic variability of 16p11.2DS.
16p11.2缺失综合征（16p11.2DS）是一种反复出现的拷贝数变异，约70%的病例为新发突变，会增加神经发育障碍的风险，包括智力残疾（ID）和自闭症谱系障碍（ASD）。本研究聚焦于发育里程碑、认知概况和纵向认知轨迹。
对24名确诊为BP4 - BP5 16p11.2DS的儿童（5 - 16岁）进行了面对面评估、查阅数字病历并与家长进行了发育史访谈，分析其发育里程碑（运动、语言、自控能力）。对所有儿童进行了标准化智力测试，部分亚组（79%，19/24）有纵向智商数据。
运动、语言和自控能力里程碑出现延迟。平均智商处于临界范围（智商71），46%（11/24）的儿童智商处于临界水平（智商70 - 84）。在五个认知领域均发现个体内和个体间的变异性，55%（11/20）的儿童在语言和非语言技能方面存在显著差异。纵向智商数据表明，患有16p11.2DS的学龄儿童在第二个时间点的表现统计学上显著更低（p < 0.001），58%的儿童呈逐渐变差的轨迹。
运动、语言和自控能力里程碑延迟在16p11.2DS携带者中很常见。患有16p11.2DS的学龄儿童随着时间推移认知障碍逐渐加重，这表明需要早期诊断、定期认知随访和个体化干预。不协调智商概况的高发生率凸显了将关注重点从全量表智商（FSIQ）结果扩展的重要性。未来需要对包括携带者亲属在内的更大队列进行研究，以更深入了解16p11.2DS的外显率和表型变异性。
