Center for Genetic Disorders of Cognition and Behavior, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Intellect Disabil Res. 2012 Mar;56(3):233-47. doi: 10.1111/j.1365-2788.2011.01404.x. Epub 2011 Mar 8.
While behavioural abnormalities are fundamental features of Rett syndrome (RTT), few studies have examined the RTT behavioural phenotype. Most of these reports have focused on autistic features, linked to the early regressive phase of the disorder, and few studies have applied standardised behavioural measures. We used a battery of standardised measures of behaviour and functioning to test the following hypotheses: (1) autistic behaviour is prominent throughout childhood in RTT; (2) autistic features are more salient in individuals with milder presentation; (3) severity of autistic behaviour is associated with a wider range of behavioural problems; and (4) specific MECP2 mutations are linked to more severe autistic behaviour.
Eighty MECP2 mutation-positive girls with RTT (aged 1.6-14.9 years) were administered: (1) the Screen for Social Interaction (SSI), a measure of autistic behaviour suited for individuals with severe communication and motor impairment; (2) the Rett Syndrome Behaviour Questionnaire (RSBQ), covering a wide range of abnormal behaviours in RTT; (3) the Vineland Adaptive Behavior Scales (VABS); and (4) a modified version of the Rett Syndrome Severity Scale (RSSS). Regression analyses examined the predictive value of age and RSSS on autistic behaviour and other behavioural abnormalities. T-tests further characterised the behavioural phenotype of individual MECP2 mutations.
While age had no significant effect on SSI or RSBQ total scores in RTT, VABS Socialization and Composite scores decreased over time. Clinical severity (i.e. RSSS) also increased with age. Surprisingly, SSI performance was not related to either RSSS or VABS Composite scores. Autistic behaviour was weakly linked with the RSBQ Hand behaviour factor scores, but not with the RSBQ Fear/Anxiety factor. Clinical (neurological) severity did not predict RSBQ scores, as evidenced by the analysis of individual MECP2 mutations (e.g. p.R106W, p.R270X and p.R294X).
Our data suggest that in RTT, autistic behaviour persists after the period of regression. It also demonstrated that neurological and behavioural impairments, including autistic features, are relatively independent of one another. Consistent with previous reports of the RTT phenotype, individual MECP2 mutations demonstrate complex associations with autistic features. Evidence of persistent autistic behaviour throughout childhood, and of a link between hand function and social skills, has important implications not only for research on the RTT behavioural phenotype, but also for the clinical management of the disorder.
行为异常是雷特综合征（RTT）的基本特征，但很少有研究检查 RTT 的行为表型。这些报告大多集中在自闭症特征上，与疾病的早期退行阶段有关，很少有研究应用标准化的行为测量。我们使用一系列标准化的行为和功能测量来检验以下假设：（1）自闭症行为在 RTT 儿童期普遍存在；（2）自闭症特征在表现较轻的个体中更为突出；（3）自闭症行为的严重程度与更广泛的行为问题相关；（4）特定的 MECP2 突变与更严重的自闭症行为有关。
对 80 名 MECP2 突变阳性的 RTT 女孩（年龄 1.6-14.9 岁）进行了以下测试：（1）社交互动筛查（SSI），一种适合严重沟通和运动障碍个体的自闭症行为测量；（2）雷特综合征行为问卷（RSBQ），涵盖 RTT 中广泛的异常行为；（3）文兰适应行为量表（VABS）；（4）雷特综合征严重程度量表（RSSS）的修改版。回归分析检验了年龄和 RSSS 对自闭症行为和其他行为异常的预测价值。T 检验进一步描述了个体 MECP2 突变的行为表型。
虽然年龄对 RTT 中的 SSI 或 RSBQ 总分没有显著影响，但 VABS 社交和综合评分随时间下降。临床严重程度（即 RSSS）也随年龄增加而增加。令人惊讶的是，SSI 表现与 RSSS 或 VABS 综合评分均无关。自闭症行为与 RSBQ 手部行为因子评分呈弱相关，但与 RSBQ 恐惧/焦虑因子无关。临床（神经学）严重程度并不能预测 RSBQ 评分，这一点可以从对个体 MECP2 突变的分析中得到证明（例如，p.R106W、p.R270X 和 p.R294X）。
我们的数据表明，在 RTT 中，自闭症行为在退行期后仍持续存在。它还表明，神经和行为损伤，包括自闭症特征，彼此相对独立。与之前报道的 RTT 表型一致，个体 MECP2 突变与自闭症特征存在复杂的关联。自闭症行为在整个儿童期持续存在，以及手部功能与社交技能之间的联系，不仅对 RTT 行为表型的研究具有重要意义，而且对该疾病的临床管理也具有重要意义。
