Phenotypic and Imaging Spectrum Associated With WDR45.
Background: Mutations in the X-linked gene WDR45 cause neurodegeneration with brain iron accumulation type 5. Global developmental delay occurs at an early age with slow progression to dystonia, parkinsonism, and dementia due to progressive iron accumulation in the brain.Methods: We present 17 new c...
| Publicado en: | Pediatric Neurology Vol. 109; pp. 56 - 63 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Elsevier B.V.
Aug2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=144713349&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 144713349 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 08878994 JNS jtl: Pediatric Neurology issn: 08878994 maglogo: N pubinfo: dt: Aug2020 vid: 109 pid: 467 pub: Elsevier B.V. place: New York, New York artinfo: ui: 144713349 144713349 NLM32387008 144713349 10.1016/j.pediatrneurol.2020.03.005 NLM32387008 144713349 ppf: 56 ppct: 7 formats: tig: atl: Phenotypic and Imaging Spectrum Associated With WDR45. aug: au: 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 affil: Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania sug: subj: Developmental Disabilities Diagnosis Developmental Disabilities Developmental Disabilities Etiology Epilepsy Physiopathology Epilepsy Diagnosis Brain Diseases Physiopathology Iron Metabolism Disorders Complications Demyelinating Diseases Iron Metabolism Disorders Brain Diseases Diagnosis Brain Diseases Complications Iron Metabolism Disorders Diagnosis Epilepsy Brain Diseases Demyelinating Diseases Physiopathology Demyelinating Diseases Etiology Iron Metabolism Disorders Physiopathology Demyelinating Diseases Diagnosis Epilepsy Etiology Carrier Proteins Developmental Disabilities Physiopathology Adolescence Adult Human Phenotype Child, Preschool Young Adult Infant Prospective Studies Child Middle Age Female Male Comparative Studies Multicenter Studies Evaluation Research Validation Studies Scales Funding Source Adolescent: 13-18 years Adult: 19-44 years Child, Preschool: 2-5 years Infant: 1-23 months Child: 6-12 years Middle Aged: 45-64 years Female Male ab: Background: Mutations in the X-linked gene WDR45 cause neurodegeneration with brain iron accumulation type 5. Global developmental delay occurs at an early age with slow progression to dystonia, parkinsonism, and dementia due to progressive iron accumulation in the brain.Methods: We present 17 new cases and reviewed 106 reported cases of neurodegeneration with brain iron accumulation type 5. 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. Although 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 in half of our cohort and was associated with older age of image acquisition, whereas myelination abnormalities were associated with younger age.Conclusions: WDR45 mutations lead to a progressive and evolving disorder whose diagnosis is often delayed. Developmental delay and seizures predominate in early childhood, followed by a progressive decline of neurological 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. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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