title: Phenotype Differentiation of FOXG1 and MECP2 Disorders: A New Method for Characterization of Developmental Encephalopathies.
abstract: OBJECTIVE
  To differentiate developmental encephalopathies by creating a novel quantitative phenotyping tool.
  
  
  METHODS
  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.
authors.affiliation: University of Buffalo School of Medicine, Buffalo, NY.
authors.forename: Mandy
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Neurology, University of Rochester Medical Center, Rochester, NY.
authors.forename: Heather R
authors.initials: HR
authors.lastname: Adams
authors.affiliation: Department of Neurology, University of Rochester Medical Center, Rochester, NY; Strong Epilepsy Center, University of Rochester Medical Center, Rochester, NY.
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Seltzer
authors.affiliation: Department of Neurology, University of Washington, Seattle, WA; Division of Medical Genetics, Department of Pediatrics, University of Washington, Seattle, WA; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA.
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.affiliation: Department of Neurology, University of Rochester Medical Center, Rochester, NY; Departments of Pediatrics and Biomedical Genetics, University of Rochester Medical Center, Rochester, NY; Center for Neural Development and Disease, University of Rochester Medical Center, Rochester, NY. Electronic address: Alex_Paciorkowski@urmc.rochester.edu.
authors.forename: Alex R
authors.initials: AR
authors.lastname: Paciorkowski
mesh_terms: D001927:Brain Diseases / Q000175:diagnosis*; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype
chemical_list: C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins
keywords: FOXG1; MECP2; autism; developmental encephalopathy; intellectual disability; natural history; quantitative phenotyping