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

Mandy Ma, Heather R. Adams, Laurie E. Seltzer, William B. Dobyns, Alex R. Paciorkowski

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Objective 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.

Original languageEnglish (US)
Pages (from-to)233-240.e10
JournalJournal of Pediatrics
Volume178
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
Supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (R01NS058721 [to W.D.] and K08NS078054 [to A.P.]). The authors declare no conflicts of interest. Original Articles

Funding Information:
We acknowledge the FOXG1 Foundation, as well as Susan Hyman, MD (supported by the National Institute of Mental Health [R34 MH100254]), Alan Percy, MD (supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD; U54 HD0612222], Neuron Pharmaceuticals, and the Civitan International Research Center), Jeffrey Neul, MD (supported by NICHD [U54 HD083092] and National Institute of Neurological Disorders and Stroke [NINDS; R21 NS089366]), and Timothy Benke, MD (supported by NINDS [P30 NS048154]), for referring subjects to this study.

Publisher Copyright:
© 2016 Elsevier Inc.

Keywords

  • FOXG1
  • MECP2
  • autism
  • developmental encephalopathy
  • intellectual disability
  • natural history
  • quantitative phenotyping

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