Genetic Subtypes of Phelan-McDermid Syndrome Exhibit Similar Rates of Change Despite Differences in Level of Impairment in Developmental Constructs.

IF 2 4区 医学 Q1 EDUCATION, SPECIAL
Tess Levy, Cristan Farmer, Siddharth Srivastava, Kristina Johnson, Jadyn Trayvick, Camille Brune, Alexandra Massa, Hailey Silver, Paige M Siper, Jessica Zweifach, Danielle Halpern, Jennifer H Foss-Feig, Jonathan A Bernstein, Elizabeth Berry-Kravis, Craig M Powell, Mustafa Sahin, Latha Valluripalli Soorya, Audrey Thurm, Joseph D Buxbaum, Alexander Kolevzon
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Abstract

The clinical spectrum of Phelan-McDermid syndrome (PMS) is varied, with wide-ranging degrees of intellectual disability, developmental delays, behavioral abnormalities, and medical features. Different types of genetic variation lead to PMS, and differing genotypes (e.g., size of deletion or type of variant) account for some of this variability, with strong associations between genotype and phenotype observed with degree of intellectual disability and presence of specific medical features such as renal abnormalities. To date, no studies have assessed how genotype is associated with the natural history of developmental or behavioral features in PMS over time. Here, we report on longitudinal data in developmental and behavioral domains from 154 individuals with PMS, comparing those with Class 1 (minimal) deletions, Class 2 deletions, and sequence variants, assessing both within-subject (individual change over time) and between-subject (across age) differences. Consistent with previous results, average scores per group differed in most adaptive and developmental domains, with individuals with Class 1 deletions performing best, followed by individuals with Class 2 deletions and sequence variants, who often performed similarly. However, in most domains of adaptive behavior, intellectual functioning, and behavioral features, genetic groups did not differ in their rate of change over time or in differences in scores across ages. Exceptions, notably in expressive language, existed. These results suggest that, although genotype may be related to overall degree of impairment, individuals with PMS, regardless of genotype, tend to have a similar rate of change over time and age in developmental and behavioral domains. A significant caveat is that sequencing is a relatively recent diagnostic approach, which will bias the results.

费兰-麦克德米综合征的遗传亚型表现出相似的变化率,尽管在发育结构的损伤水平上存在差异。
Phelan-McDermid综合征(PMS)的临床谱系是多种多样的,具有广泛程度的智力残疾、发育迟缓、行为异常和医学特征。不同类型的遗传变异导致经前症候群,不同的基因型(例如,缺失的大小或变异的类型)在一定程度上解释了这种变异,基因型和表型之间存在很强的关联,这与智力残疾的程度和肾脏异常等特定医学特征的存在有关。迄今为止,还没有研究评估基因型如何与经前症候群的发育或行为特征的自然史相关联。在这里,我们报告了154名经前综合症患者在发育和行为领域的纵向数据,比较了1类(最小)缺失、2类缺失和序列变异,评估了受试者内部(个体随时间变化)和受试者之间(跨越年龄)的差异。与之前的结果一致,每组在大多数适应和发育领域的平均得分不同,1类缺失的个体表现最好,其次是2类缺失和序列变异的个体,他们的表现通常相似。然而,在适应性行为、智力功能和行为特征的大多数领域,基因组在其随时间的变化率或不同年龄的得分差异方面没有差异。例外是存在的,尤其是在表达性语言中。这些结果表明,尽管基因型可能与整体损害程度有关,但经前综合症患者,无论基因型如何,在发育和行为领域随着时间和年龄的变化往往具有相似的变异性。一个重要的警告是,测序是一种相对较新的诊断方法,这将使结果产生偏差。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.10
自引率
4.80%
发文量
47
期刊介绍: The American Journal on Intellectual and Developmental Disabilities (Print ISSN: 1944–7515; Online ISSN: 1944–7558) is published by the American Association on Intellectual and Developmental Disabilities. It is a scientifi c, scholarly, and archival multidisciplinary journal for reporting original contributions of the highest quality to knowledge of intellectual disabilities, its causes, treatment, and prevention.
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