title: PEHO Syndrome May Represent Phenotypic Expansion at the Severe End of the Early-Onset Encephalopathies.
abstract: Progressive encephalopathy with edema, hypsarrhythmia and optic atrophy (PEHO) syndrome is a distinct neurodevelopmental disorder. Patients without optic nerve atrophy and brain imaging abnormalities but fulfilling other PEHO criteria are often described as a PEHO-like syndrome. The molecular bases of both clinically defined conditions remain unknown in spite of the widespread application of genome analyses in both clinic and research.
  
  
  
  We enrolled two patients with a prior diagnosis of PEHO and two individuals with PEHO-like syndrome. All four individuals subsequently underwent whole-exome sequencing and comprehensive genomic analysis.
  
  
  
  We identified disease-causing mutations in known genes associated with neurodevelopmental disorders including GNAO1 and CDKL5 in two of four individuals. One patient with PEHO syndrome and a de novoGNAO1 mutation was found to have an additional de novo mutation in HESX1 that is associated with optic atrophy.
  
  
  
  We hypothesize that PEHO and PEHO-like syndrome may represent a severe end of the spectrum of the early-onset encephalopathies and, in some instances, its complex phenotype may result from an aggregated effect of mutations at two loci.
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Gawlinski
authors.affiliation: Department of Clinical Genetics, Podlaskie Medical Center, Bialystok, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Posmyk
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland; Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gambin
authors.affiliation: Department of Pediatric Ophthalmology, Children's University Hospital, Bialystok, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Sielicka
authors.affiliation: Department of Neurology, Medical University Hospital, Bialystok, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Chorazy
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Nowakowska
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Shalini N
authors.initials: SN
authors.lastname: Jhangiani
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.affiliation: Department of Diagnostic Imaging, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Bekiesinska-Figatowska
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bal
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas; Human Genetics Center and Institute of Molecular Medicine, University of Texas-Houston Health Science Center, Houston, Texas.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas; Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Texas Children's Hospital, Houston, Texas.
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas. Electronic address: wkw@bcm.edu.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Wiszniewski
mesh_terms: D001929:Brain Edema / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D009896:Optic Atrophy / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D013036:Spasms, Infantile / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology
chemical_list: C584143:GNAO1 protein, human; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: PEHO; encephalopathy; neurodevelopmental disorder; optic atrophy; whole-exome sequencing