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Pediatr Neurol. 2016 Jul;60:83-7. doi: 10.1016/j.pediatrneurol.2016.03.011. Epub 2016 Apr 9.

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

Author information

1
Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
2
Department of Clinical Genetics, Podlaskie Medical Center, Bialystok, Poland.
3
Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland; Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland.
4
Department of Pediatric Ophthalmology, Children's University Hospital, Bialystok, Poland.
5
Department of Neurology, Medical University Hospital, Bialystok, Poland.
6
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
7
Department of Diagnostic Imaging, Institute of Mother and Child, Warsaw, Poland.
8
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.
9
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.
10
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.

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.

KEYWORDS:

PEHO; encephalopathy; neurodevelopmental disorder; optic atrophy; whole-exome sequencing

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

J.R.L. has stock ownership in 23andMe and Lasergen and is a paid consultant for Regeneron. J.R.L. is a coinventor on multiple U.S. and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis and clinical exome sequencing offered in the Baylor Medical Genetics Laboratories (http://www.bcm.edu/geneticlabs/). Other authors have no disclosures relevant to the article.

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