Phenotype Differentiation of FOXG1 and MECP2 Disorders: A New Method for Characterization of Developmental Encephalopathies

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• 作者：Mandy Ma ; BS¹ ; Heather R. Adams ; PhD² ; Laurie E. Seltzer ; DO² ; ³ ; William B. Dobyns ; MD⁴ ; ⁵ ; ⁶ ; Alex R. Paciorkowski ; MD² ; ⁷ ; ⁸ ; ^{Alex_Paciorkowski@urmc.rochester.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：FOXG1 ; MECP2 ; developmental encephalopathy ; autism ; intellectual disability ; quantitative phenotyping ; natural history
• 刊名：The Journal of Pediatrics
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：178
• 期：Complete
• 页码：233-240.e10
• 全文大小：2470 K

文摘

To differentiate developmental encephalopathies by creating a novel quantitative phenotyping tool.

Study design

We created the Developmental Encephalopathy Inventory (DEI) to differentiate disorders with complex multisystem neurodevelopmental symptoms. We then used the DEI to study the phenotype features of 20 subjects with FOXG1 disorder and 11 subjects with MECP2 disorder.

Results

The DEI identified core domains of fine motor and expressive language that were severely impaired in both disorders. Individuals with FOXG1 disorder were overall more severely impaired. Subjects with FOXG1 disorder were less able to walk, had worse fine motor skills, more disability in receptive language and reciprocity, and had more disordered sleep than did subjects with MECP2 disorder (P < .05). Covariance, cluster, and principal component analysis confirmed a relationship between impaired awareness, reciprocity, and language in both disorders. In addition, abnormal ambulation was a first principal component for FOXG1 but not for MECP2 disorder, suggesting that impaired ambulation is a strong differentiating factor clinically between the 2 disorders.

Conclusions

We have developed a novel quantitative developmental assessment tool for developmental encephalopathies and propose this tool as a method to identify and illustrate core common and differential domains of disability in these complex disorders. These findings demonstrate clear phenotype differences between FOXG1 and MECP2 disorders.