title: PLA2G6-associated neurodegeneration (PLAN): further expansion of the clinical, radiological and mutation spectrum associated with infantile and atypical childhood-onset disease.
abstract: Phospholipase A2 associated neurodegeneration (PLAN) is a major phenotype of autosomal recessive Neurodegeneration with Brain Iron Accumulation (NBIA). We describe the clinical phenotypes, neuroimaging features and PLA2G6 mutations in 5 children, of whom 4 presented with infantile neuroaxonal dystrophy (INAD). One other patient was diagnosed with the onset of PLAN in childhood, and our report highlights the diagnostic challenges associated with this atypical PLAN subtype. In this series, the neuroradiological relevance of classical PLAN features as well as apparent claval hypertrophy' is explored. Novel PLA2G6 mutations were identified in all patients. PLAN should be considered not only in patients presenting with a classic INAD phenotype but also in older patients presenting later in childhood with non-specific progressive neurological features including social communication difficulties, gait disturbance, dyspraxia, neuropsychiatric symptoms and extrapyramidal motor features.
authors.affiliation: Department of Neurology, Great Ormond Street Hospital, London, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Illingworth
authors.affiliation: Neurosciences Unit, UCL-Institute of Child Health, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Meyer
authors.affiliation: Department of Radiology, Great Ormond Street Hospital, London, UK.
authors.forename: W K
authors.initials: WK
authors.lastname: Chong
authors.affiliation: Dubowitz Neuromuscular Centre for Congenital Muscular Dystrophies and Myopathies, Great Ormond Street Hospital, London, UK.
authors.forename: A Y
authors.initials: AY
authors.lastname: Manzur
authors.affiliation: Department of Neurology, Great Ormond Street Hospital, London, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Carr
authors.affiliation: West Midlands Regional Genetics, Birmingham Women's Hospital, Birmingham, UK.
authors.forename: R
authors.initials: R
authors.lastname: Younis
authors.affiliation: West Midlands Regional Genetics, Birmingham Women's Hospital, Birmingham, UK.
authors.forename: C
authors.initials: C
authors.lastname: Hardy
authors.affiliation: West Midlands Regional Genetics, Birmingham Women's Hospital, Birmingham, UK.
authors.forename: F
authors.initials: F
authors.lastname: McDonald
authors.affiliation: Department of Paediatric Neurology, Leeds General Infirmary, Leeds, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Childs
authors.affiliation: Department of Paediatrics, York Teaching Hospitals NHS Foundation Trust, York, UK.
authors.forename: B
authors.initials: B
authors.lastname: Stewart
authors.affiliation: Department of Neuroradiology, Leeds teaching Hospitals, Leeds. UK.
authors.forename: D
authors.initials: D
authors.lastname: Warren
authors.affiliation: Department of Neurology, Alder Hey Children's Hospital, Liverpool, UK.
authors.forename: R
authors.initials: R
authors.lastname: Kneen
authors.affiliation: Department of Paediatric Neurology, Children's University Hospital, Temple Street, Dublin, Ireland.
authors.forename: M D
authors.initials: MD
authors.lastname: King
authors.affiliation: Department of Molecular & Medical Genetics, OR Health & Science University, Portland 97239, USA; Department of Paediatrics, OR Health & Science University, Portland 97239, USA; Department of Neurology, OR Health & Science University, Portland 97239, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hayflick
authors.affiliation: Department of Neurology, Great Ormond Street Hospital, London, UK; Neurosciences Unit, UCL-Institute of Child Health, London, UK. Electronic address: manju.kurian@ucl.ac.uk.
authors.forename: M A
authors.initials: MA
authors.lastname: Kurian
mesh_terms: D017668:Age of Onset; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D006801:Humans; D007223:Infant; D007494:Ireland; D008297:Male; D009154:Mutation; D019150:Neuroaxonal Dystrophies / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D011859:Radiography; D006113:United Kingdom
chemical_list: D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human
keywords: INAD; NBIA; Neurodegeneration with brain iron accumulation; PLA2G6; PLAN
references.citation: Am J Hum Genet. 2011 Oct 7;89(4):543-50
references.pmid: 21981780
references.citation: J Med Genet. 2009 Feb;46(2):73-80
references.pmid: 18981035
references.citation: Dev Med Child Neurol. 2011 May;53(5):394-404
references.pmid: 21480873
references.citation: Ann Neurol. 2009 Jan;65(1):19-23
references.pmid: 18570303
references.citation: J Biol Chem. 1998 Jan 2;273(1):207-14
references.pmid: 9417066
references.citation: J Neurosci. 2011 Aug 3;31(31):11411-20
references.pmid: 21813701
references.citation: Neurology. 2008 Apr 29;70(18):1623-9
references.pmid: 18443314
references.citation: Mol Genet Metab. 2010 Jun;100(2):207-12
references.pmid: 20226704
references.citation: PLoS One. 2013 Oct 09;8(10):e76831
references.pmid: 24130795
references.citation: J Neurol Sci. 2012 Nov 15;322(1-2):254-62
references.pmid: 22669122
references.citation: Cell Signal. 2005 Sep;17(9):1052-62
references.pmid: 15993747
references.citation: Am J Pathol. 2008 Feb;172(2):406-16
references.pmid: 18202189
references.citation: Neurology. 2010 Oct 12;75(15):1356-61
references.pmid: 20938027
references.citation: Am J Pathol. 2009 Dec;175(6):2257-63
references.pmid: 19893029
references.citation: Neurology. 2008 Oct 28;71(18):1402-9
references.pmid: 18799783
references.citation: J Neurosci. 2008 Feb 27;28(9):2212-20
references.pmid: 18305254
references.citation: Nat Genet. 2006 Jul;38(7):752-4
references.pmid: 16783378
references.citation: Hum Mol Genet. 2012 Jun 15;21(12):2807-14
references.pmid: 22442204
references.citation: Am J Hum Genet. 2012 Dec 7;91(6):1144-9
references.pmid: 23176820
references.citation: Acta Neuropathol Commun. 2013 May 09;1:12
references.pmid: 24252552