PEHO Syndrome May Represent Phenotypic Expansion at the Severe End of the Early-Onset Encephalopathies.

TitlePEHO Syndrome May Represent Phenotypic Expansion at the Severe End of the Early-Onset Encephalopathies.
Publication TypeJournal Article
Year of Publication2016
AuthorsGawlinski, P, Posmyk, R, Gambin, T, Sielicka, D, Chorazy, M, Nowakowska, B, Jhangiani, SN, Muzny, DM, Bekiesinska-Figatowska, M, Bal, J, Boerwinkle, E, Gibbs, RA, Lupski, JR, Wiszniewski, W
JournalPediatr Neurol
Volume60
Pagination83-7
Date Published2016 07
ISSN1873-5150
KeywordsBrain Edema, Child, Child, Preschool, Female, GTP-Binding Protein alpha Subunits, Gi-Go, Humans, Infant, Male, Mutation, Neurodegenerative Diseases, Optic Atrophy, Phenotype, Protein-Serine-Threonine Kinases, Spasms, Infantile
Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

DOI10.1016/j.pediatrneurol.2016.03.011
Alternate JournalPediatr. Neurol.
PubMed ID27343026
PubMed Central IDPMC5125779
Grant ListK23 NS078056 / NS / NINDS NIH HHS / United States
R01 NS058529 / NS / NINDS NIH HHS / United States
U54 HG006542 / HG / NHGRI NIH HHS / United States
UM1 HG006542 / HG / NHGRI NIH HHS / United States