PEHO syndrome: the endpoint of different genetic epilepsies.
Nahorski, Michael S
Wakeling, Emma L
Brady, Angela F
Zuberi, Sameer M
Parker, Alasdair PJ
J Med Genet
MetadataShow full item record
Chitre, M., Nahorski, M. S., Stouffer, K., Dunning-Davies, B., Houston, H., Wakeling, E. L., Brady, A. F., et al. (2018). PEHO syndrome: the endpoint of different genetic epilepsies.. J Med Genet, 55 (12), 803-813. https://doi.org/10.1136/jmedgenet-2018-105288
BACKGROUND: 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.
developmental, epilepsy and seizures, genetics, neurology, Age Factors, Alleles, Biomarkers, Brain Edema, Child, Preschool, Electroencephalography, Epilepsy, Facies, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Testing, Genotype, Humans, Infant, Infant, Newborn, Magnetic Resonance Imaging, Male, Mutation, Neurodegenerative Diseases, Optic Atrophy, Pedigree, Phenotype, Spasms, Infantile
External DOI: https://doi.org/10.1136/jmedgenet-2018-105288
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285865
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: email@example.com