Phenotypic and imaging spectrum associated with WDR45

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http://hdl.handle.net/10138/327777

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Adang , L A , Pizzino , A , Malhotra , A , Dubbs , H , Williams , C , Sherbini , O , Anttonen , A-K , Lesca , G , Linnankivi , T , Laurencin , C , Milh , M , Perrine , C , Schaaf , C P , Poulat , A-L , Ville , D , Hagelstrom , T , Perry , D L , Taft , R J , Goldstein , A , Vossough , A , Helbig , I & Vanderver , A 2020 , ' Phenotypic and imaging spectrum associated with WDR45 ' , Pediatric Neurology , vol. 109 , pp. 56-62 . https://doi.org/10.1016/j.pediatrneurol.2020.03.005

Title: Phenotypic and imaging spectrum associated with WDR45
Author: Adang, Laura A.; Pizzino, Amy; Malhotra, Alka; Dubbs, Holly; Williams, Catherine; Sherbini, Omar; Anttonen, Anna-Kaisa; Lesca, Gaetan; Linnankivi, Tarja; Laurencin, Chloé; Milh, Matthieu; Perrine, Charles; Schaaf, Christian P.; Poulat, Anne-Lise; Ville, Dorothee; Hagelstrom, Tanner; Perry, Denise L.; Taft, Ryan J.; Goldstein, Amy; Vossough, Arastoo; Helbig, Ingo; Vanderver, Adeline
Contributor organization: Medicum
HUSLAB
Department of Medical and Clinical Genetics
Neuroscience Center
University of Helsinki
Helsinki University Hospital Area
HUS Children and Adolescents
Date: 2020-08
Language: eng
Number of pages: 7
Belongs to series: Pediatric Neurology
ISSN: 0887-8994
DOI: https://doi.org/10.1016/j.pediatrneurol.2020.03.005
URI: http://hdl.handle.net/10138/327777
Abstract: Background Mutations in the X-linked gene WDR45 cause neurodegeneration with brain iron accumulation type 5 (NBIA5). Global developmental delay is seen at an early age with a slow progression to dystonia, parkinsonism, and dementia due to progressive iron accumulation in the brain. Methodology We present 17 new cases and reviewed 106 reported cases of NBIA5. Detailed information related to developmental history and key time to event measures was collected. Results Within this cohort, there were 19 males. Most individuals were molecularly diagnosed by whole exome testing. Overall 10 novel variants were identified across 11 subjects. All individuals were affected by developmental delay, most prominently in verbal skills. Most individuals experienced a decline in motor and cognitive skills. While most individuals were affected by seizures, the spectrum ranged from provoked seizures to intractable epilepsy. The imaging findings varied as well, often evolving over time. The classic iron accumulation in the globus pallidus and substantia nigra was noted half of our cohort and was associated with an older age of image acquisition, while myelination abnormalities were associated with a younger age. Conclusions WDR45 is a progressive and evolving disorder, which is often delayed in diagnosis. Developmental delay and seizures predominate early childhood, followed by a progressive decline of neurologic function. There is variable expressivity in the clinical phenotypes of individuals with WDR45 mutations, suggesting that this gene should be considered in the diagnostic evaluation of children with myelination abnormalities, iron deposition, developmental delay, and epilepsy depending on the age at evaluation.
Subject: 3124 Neurology and psychiatry
Hypomyelination
Epileptic encephalopathy
WDR45
Developmental delay
PROTEIN-ASSOCIATED NEURODEGENERATION
EXOME SEQUENCING REVEALS
MUTATIONS
CHILDHOOD
FEMALE
3123 Gynaecology and paediatrics
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion


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