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dc.contributor.authorChitre, Manali
dc.contributor.authorNahorski, Michael Stefan
dc.contributor.authorStouffer, Kaitlin
dc.contributor.authorDunning-Davies, Bryony
dc.contributor.authorHouston, Hamish
dc.contributor.authorWakeling, Emma L
dc.contributor.authorBrady, Angela F
dc.contributor.authorZuberi, Sameer M
dc.contributor.authorSuri, Mohnish
dc.contributor.authorParker, Alasdair PJ
dc.contributor.authorWoods, Geoff
dc.date.accessioned2018-11-23T00:33:34Z
dc.date.available2018-11-23T00:33:34Z
dc.date.issued2018-12
dc.identifier.issn0022-2593
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285865
dc.description.abstractBACKGROUND: Progressive encephalopathy, hypsarrhythmia and optic atrophy (PEHO) has been described as a clinically distinct syndrome. It has been postulated that it is an autosomal recessive condition. However, the aetiology is poorly understood, and the genetic basis of the condition has not been fully elucidated. Our objective was to discover if PEHO syndrome is a single gene disorder. METHOD: Children with PEHO and PEHO-like syndrome were recruited. Clinical, neurological and dysmorphic features were recorded; EEG reports and MRI scans were reviewed. Where possible, exome sequencing was carried out first to seek mutations in known early infantile developmental and epileptic encephalopathy (DEE) genes and then to use an agnostic approach to seek novel candidate genes. We sought intra-interfamilial phenotypic correlations and genotype-phenotype correlations when pathological mutations were identified. RESULTS: Twenty-three children were recruited from a diverse ethnic background, 19 of which were suitable for inclusion. They were similar in many of the core and the supporting features of PEHO, but there was significant variation in MRI and ophthalmological findings, even between siblings with the same mutation. A pathogenic genetic variant was identified in 15 of the 19 children. One further girl's DNA failed analysis, but her two affected sisters shared confirmed variants. Pathogenic variants were identified in seven different genes. CONCLUSIONS: We found significant clinical and genetic heterogeneity. Given the intrafamily variation demonstrated, we question whether the diagnostic criteria for MRI and ophthalmic findings should be altered. We also question whether PEHO and PEHO-like syndrome represent differing points on a clinical spectrum of the DEE. We conclude that PEHO and PEHO-like syndrome are clinically and genetically diverse entities-and are phenotypic endpoints of many severe genetic encephalopathies.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherBMJ
dc.subjectHumans
dc.subjectBrain Edema
dc.subjectEpilepsy
dc.subjectSpasms, Infantile
dc.subjectOptic Atrophy
dc.subjectNeurodegenerative Diseases
dc.subjectGenetic Predisposition to Disease
dc.subjectFacies
dc.subjectMagnetic Resonance Imaging
dc.subjectElectroencephalography
dc.subjectPedigree
dc.subjectAge Factors
dc.subjectGenotype
dc.subjectPhenotype
dc.subjectMutation
dc.subjectAlleles
dc.subjectChild, Preschool
dc.subjectInfant
dc.subjectInfant, Newborn
dc.subjectFemale
dc.subjectMale
dc.subjectGenetic Testing
dc.subjectGenetic Association Studies
dc.subjectBiomarkers
dc.titlePEHO syndrome: the endpoint of different genetic epilepsies.
dc.typeArticle
prism.endingPage813
prism.issueIdentifier12
prism.publicationDate2018
prism.publicationNameJ Med Genet
prism.startingPage803
prism.volume55
dc.identifier.doi10.17863/CAM.33209
dcterms.dateAccepted2018-08-17
rioxxterms.versionofrecord10.1136/jmedgenet-2018-105288
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-12
dc.contributor.orcidWoods, Geoff [0000-0002-8077-2101]
dc.identifier.eissn1468-6244
rioxxterms.typeJournal Article/Review
cam.issuedOnline2018-10-04
rioxxterms.freetoread.startdate2019-10-04


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