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

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• 作者：Pawel Gawlinski ; PhD^a ; Renata Posmyk ; MD^b ; Tomasz Gambin ; PhD^a ; ^c ; Danuta Sielicka ; MD^d ; Monika Chorazy ; MD^e ; Beata Nowakowska ; PhD^a ; Shalini N. Jhangiani ; MSc^f ; Donna M. Muzny ; MSc^f ; Monika Bekiesinska-Figatowska ; MD ; PhD^g ; Jerzy Bal ; PhD^a ; Eric Boerwinkle ; PhD^f ; ^h ; Richard A. Gibbs ; PhD^f ; James R. Lupski ; MD ; PhD ; DSc (hon)^f ; ⁱ ; ^j ; ^k ; Wojciech Wiszniewski ; MD ; PhD^a ; ⁱ ; ^{wkw@bcm.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PEHO ; encephalopathy ; whole-exome sequencing ; optic atrophy ; neurodevelopmental disorder
• 刊名：Pediatric Neurology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：60
• 期：Complete
• 页码：83-87
• 全文大小：743 K

文摘

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.