臺灣雷特氏症兒童的多元向度發展及其發展能力與自閉類群障礙兒童之比較

Multidimensional Developments in Taiwanese Children with Rett Syndrome and Comparing Developmental Abilities to Children with Autism Spectrum Disorder

王詩雅(Shih-Ya Wang)

指導教授 ： 吳晏慈

國立臺灣大學/醫學院/物理治療學研究所/碩士(2019年)

https://doi.org/10.6342/NTU201902943

摘要

雷特氏症(Rett Syndrome；簡稱RTT)，是一種X染色體性聯遺傳的神經發展疾病，常見的基因突變點位於MECP2基因上。雷特氏症患者的臨床症狀為嚴重的認知、社會溝通與動作發展障礙、以及重覆性的手部刻板動作。目前尚無研究使用標準化的發展測量工具評估雷特氏症兒童的多元向度發展，以及比較不同基因突變型之雷特氏症兒童的發展型態。此外，雷特氏症兒童的早期發展與行為特質與患有自閉症類群障礙(Autism Spectrum Disorder)且共病智能障礙的兒童相似，因此使得兩種疾病的早期辨識產生混淆，然而，目前仍極少研究比較雷特氏症與自閉症類群共病智能障礙兒童的多元發展。因此，本研究目的為探討雷特氏症兒童的多元向度發展，包括認知、語言、動作、行為與社會溝通發展, 並與患有自閉症類群共病智能障礙或正常發展兒童做比較。本研究共招募30名患有雷特氏症兒童攜帶MECP2基因型變異(簡稱雷特-MECP2組)，7名雷特氏症兒童攜帶其他基因型突變(簡稱其他變異組)，26名自閉症類群共病智能障礙之兒童，及37名正常發展兒童參與本研究。本研究使用「穆林早期學習量表」評估兒童的粗動作與精細動作、視覺接受、及接受與表達語言的發展。同時家長填寫「文蘭適應行為量表編譯版」、「中文版兒童生活功能量表」、以及「重複行為量表修訂版」評估生活中的適應行為、日常功能及重複行為。此外，使用「早期社會溝通量表」，進行多種標準化遊戲，以評估孩童在非語言行為的反應與社會溝通技巧。本研究使用曼-惠特尼U檢驗各項發展指標在雷特-MECP2和其他變異組兒童的發展差異，並使用克拉斯卡－瓦立斯檢定比較雷特氏症、自閉症類群共病智能障礙兒童，以及正常發展兒童在各項發展能力上的差異。研究結果顯示，雷特-MECP2與其他變異組的兒童在多項發展上顯示相似程度的發展能力與行為表現，然而雷特-MECP2組兒童在生活功能之自我照顧能力的分數比其他變異組顯著較高。此外，雷特-MECP2組在使用交替的眼睛注視之共同注意力、以及使用眼神接觸發起行為請求與社交互動行為，都較雷特-其他組展現更高頻率的行為表現。此外，與患有自閉症類群共病智能障礙兒童及正常發展兒童相比，雷特氏症兒童具有整體落後的認知，語言，及動作發展，然而雷特氏症與自閉症類群共病智能障礙兒童同時具有高程度的刻板行為和自我傷害行為。此外，雷特氏症較自閉症類群兒童展現更多的交替的眼睛注視之共同注意力，以及使用眼神接觸發起行為請求，然而雷特氏症兒童較少使用伸手取物的行為請求進行社會互動。本篇研究能夠提供雷特氏症兒童在多元向度的發展能力結果，並且能幫助醫療專業人員早期辨識雷特氏症與自閉類群障礙兒童的發展特徵，以提供早期診斷與介入。

關鍵字

雷特氏症 ； 兒童發展 ； 標準測驗 ； 基因 ； 自閉症類群障礙

並列摘要

Background and Purposes: Rett Syndrome (RTT) is an X-linked neurodevelopmental disorder that is commonly linked to methyl-CpG-binding protein 2 (MECP2) mutations. The clinical features of RTT are characterized by severe intellectual disability (ID), autistic-like traits and stereotypic hand movements. To date, few studies have used standardized developmental assessment tools to assess the multidimensional developments of Taiwanese children with RTT or compare developmental functions in children with RTT with different types of gene mutations. In addition, the developmental and behavioral traits of children with RTT at early ages are similar to those of children with autism spectrum disorder (ASD) and co-occurrence of ID (called ASD-ID). Therefore, RTT could be confused with ASD at the time of early identification and diagnosis. However, comparing developmental abilities in children with RTT to children with ASD-ID have rarely been investigated. Therefore, the present study investigated cognitive, language, motor, behavioral and social communication developments in children with RTT, and to compare their developmental abilities to children with ASD-ID or typical developing (TD) children. Methods: In total, 30 children with RTT who carry MECP2 gene mutation (called RTT-MECP2), 7 carry other gene mutations (called RTT-variants), 26 children with ASD-ID and 37 TD children participated in this study. All participants’ cognitive, language and motor developments were assessed using the Mullen Scales of Early Learning (MSEL). Child’s adaptive behaviors and daily functions were assessed using the Vineland Adaptive Behavior Scales, Chinese Version of Pediatric Evaluation of Disability Inventory, and Repetitive Behavior Scale-Revised. Child’s nonverbal communication skills were assessed using the Early Social Communication Scale. The Mann–Whitney U test was used to examine the differences in developmental indicators between the children in RTT-MECP2 and RTT-variants groups. Furthermore, the Kruskal-Wallis one-way ANOVA test was conducted to compare developmental abilities among children with RTT, children with ASD-ID and TD children. Results: The results showed comparable scores or developmental equivalent ages in all MSEL subscales (all p’s >0.05) between RTT-MECP2 and RTT-variants groups. However, the scores of self-care skills were higher in the RTT-MECP2 than in the RTT-variants groups (p = 0.04). Children in the RTT-MECP2 group displayed higher frequencies of alternate eye gazes in the initiate joint attention (IJA), eye contacts in the initiate behavioral request (IBR) and response to social interaction (RSI) than children in the RTT-variants group did (all p’s > 0.05). In addition, children with RTT exhibited overall poor developmental abilities compared with children with ASD-ID and TD children in multiple developmental domains, whereas comparable degrees in stereotyped and self-injurious behaviors between the RTT and ASD-ID groups (both p’s > 0.05). Moreover, children with RTT demonstrated higher frequencies of alternate eye gazes in the IJA (p = 0.01) and eye contacts in the IBR (p < 0.01), but lower frequencies of reaching movement in the IBR (p = 0.02) than the children with ASD-ID did. Clinical professionals should aware of the crucial developmental indicators for differentiating children with RTT from children with ASD-ID. Furthermore, our findings highlight the needs of comprehensive assessments and early interventions on multidimensional developments for children with RTT.

並列關鍵字

RTT ； Development ； Standardized test ； Gene ； ASD ； Children

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