PDF(Pubmed)
Abstract：
BACKGROUND: Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder caused by SHANK3 haploinsufficiency and is associated with an increased risk for seizures. Previous literature indicates that around one third of individuals with PMS also have epilepsy or seizures, with a wide range of types and ages of onset. Investigating the impact of seizures on intellectual and adaptive functioning for PMS is a primary concern for caregivers and is important to understanding the natural history of this syndrome.
METHODS: We report on results from 98 individuals enrolled in a prospective, longitudinal study. We detailed seizure frequency, type, and age of onset, and we analyzed seizure occurrence with best estimate IQ, adaptive functioning, clinical features, and genotype. We conducted multiple linear regression analyses to assess the relationship between the presence of seizures and the Vineland Adaptive Behavior Scale, Second Edition (VABS-II) Adaptive Behavior Composite score and the best estimate full-scale IQ. We also performed Chi-square tests to explore associations between seizure prevalence and genetic groupings. Finally, we performed Chi-square tests and t-tests to explore the relationship between seizures and demographic features, features that manifest in infancy, and medical features.
RESULTS: Seizures were present in 41% of the cohort, and age of onset was widely variable. The presence of seizures was associated with significantly lower adaptive and intellectual functioning. Genotype-phenotype analyses were discrepant, with no differences in seizure prevalence across genetic classes, but with more genes included in deletions of participants with 22q13 deletions and seizures compared to those with 22q13 deletions and no seizures. No clinical associations were found between the presence of seizures and sex, history of pre- or neonatal complications, early infancy, or medical features. In this cohort, generalized seizures were associated with developmental regression, which is a top concern for PMS caregivers.
CONCLUSIONS: These results begin to eludicate correlates of seizures in individuals with PMS and highlight the importance of early seizure management. Importantly, presence of seizures was associated with adaptive and cognitive functioning. A larger cohort might be able to identify additional associations with medical features. Genetic findings suggest an increased capability to realize genotype-phenotype relationships when deletion size is taken into account.
METHODS: We report on results from 98 individuals enrolled in a prospective, longitudinal study. We detailed seizure frequency, type, and age of onset, and we analyzed seizure occurrence with best estimate IQ, adaptive functioning, clinical features, and genotype. We conducted multiple linear regression analyses to assess the relationship between the presence of seizures and the Vineland Adaptive Behavior Scale, Second Edition (VABS-II) Adaptive Behavior Composite score and the best estimate full-scale IQ. We also performed Chi-square tests to explore associations between seizure prevalence and genetic groupings. Finally, we performed Chi-square tests and t-tests to explore the relationship between seizures and demographic features, features that manifest in infancy, and medical features.
RESULTS: Seizures were present in 41% of the cohort, and age of onset was widely variable. The presence of seizures was associated with significantly lower adaptive and intellectual functioning. Genotype-phenotype analyses were discrepant, with no differences in seizure prevalence across genetic classes, but with more genes included in deletions of participants with 22q13 deletions and seizures compared to those with 22q13 deletions and no seizures. No clinical associations were found between the presence of seizures and sex, history of pre- or neonatal complications, early infancy, or medical features. In this cohort, generalized seizures were associated with developmental regression, which is a top concern for PMS caregivers.
CONCLUSIONS: These results begin to eludicate correlates of seizures in individuals with PMS and highlight the importance of early seizure management. Importantly, presence of seizures was associated with adaptive and cognitive functioning. A larger cohort might be able to identify additional associations with medical features. Genetic findings suggest an increased capability to realize genotype-phenotype relationships when deletion size is taken into account.
摘要：
背景：Phelan-McDermid综合征（PMS）是一种由SHANK3单倍体功能不全引起的遗传性神经发育障碍，与癫痫发作风险增加相关。以前的文献表明，大约三分之一的PMS患者也有癫痫或癫痫发作，具有广泛的发病类型和年龄。调查癫痫发作对PMS的智力和适应性功能的影响是护理人员的主要关注点，对于了解该综合征的自然史很重要。
方法：我们报告了98名参与者的结果，纵向研究。我们详细说明了癫痫发作频率，type,和发病年龄，我们用最好的估计智商分析了癫痫发作的发生，适应性功能，临床特征,和基因型。我们进行了多元线性回归分析，以评估癫痫发作的存在与Vineland适应行为量表之间的关系。第二版(VABS-II)自适应行为综合得分和最佳估计全面智商。我们还进行了卡方检验，以探索癫痫发作患病率和遗传分组之间的关联。最后,我们进行了卡方检验和t检验来探讨癫痫发作与人口统计学特征之间的关系，在婴儿期表现出来的特征，和医学特征。
结果：41%的人群出现癫痫发作，发病年龄差异很大。癫痫发作的存在与显着降低的适应性和智力功能有关。基因型-表型分析不一致，不同基因类别的癫痫患病率没有差异，但与22q13缺失和癫痫发作的参与者相比，22q13缺失和癫痫发作的缺失中包含更多基因。没有发现癫痫发作和性别之间的临床关联，术前或新生儿并发症的历史，早期婴儿期,或医疗特征。在这个队列中，全身性癫痫发作与发育消退有关，这是PMS护理人员最关心的问题。
结论：这些结果开始阐明PMS患者癫痫发作的相关性，并强调早期癫痫发作管理的重要性。重要的是,癫痫发作的存在与适应性和认知功能相关.更大的群体可能能够识别与医学特征的额外关联。遗传发现表明，当考虑到缺失大小时，实现基因型-表型关系的能力增强。
方法：我们报告了98名参与者的结果，纵向研究。我们详细说明了癫痫发作频率，type,和发病年龄，我们用最好的估计智商分析了癫痫发作的发生，适应性功能，临床特征,和基因型。我们进行了多元线性回归分析，以评估癫痫发作的存在与Vineland适应行为量表之间的关系。第二版(VABS-II)自适应行为综合得分和最佳估计全面智商。我们还进行了卡方检验，以探索癫痫发作患病率和遗传分组之间的关联。最后,我们进行了卡方检验和t检验来探讨癫痫发作与人口统计学特征之间的关系，在婴儿期表现出来的特征，和医学特征。
结果：41%的人群出现癫痫发作，发病年龄差异很大。癫痫发作的存在与显着降低的适应性和智力功能有关。基因型-表型分析不一致，不同基因类别的癫痫患病率没有差异，但与22q13缺失和癫痫发作的参与者相比，22q13缺失和癫痫发作的缺失中包含更多基因。没有发现癫痫发作和性别之间的临床关联，术前或新生儿并发症的历史，早期婴儿期,或医疗特征。在这个队列中，全身性癫痫发作与发育消退有关，这是PMS护理人员最关心的问题。
结论：这些结果开始阐明PMS患者癫痫发作的相关性，并强调早期癫痫发作管理的重要性。重要的是,癫痫发作的存在与适应性和认知功能相关.更大的群体可能能够识别与医学特征的额外关联。遗传发现表明，当考虑到缺失大小时，实现基因型-表型关系的能力增强。
