title: Ophthalmic features of PLA2G6-related paediatric  neurodegeneration with brain iron accumulation.
abstract: BACKGROUND
  Neurodegeneration with brain iron accumulation (NBIA) refers to genetically heterogenous paediatric neurodegenerative disorders characterised by basal ganglia iron deposition. One major cause is recessive mutations in the PLA2G6 gene. While strabismus and optic nerve pallor have been reported for PLA2G6-related disease, the ophthalmic phenotype is not carefully defined. In this study we characterise the ophthalmic phenotype of PLA2G6-related NBIA.
  
  
  METHODS
  Prospective cohort study.
  
  
  RESULTS
  The eight patients were 4-26 years old when examined. All had progressive cognitive and motor regression first noted between 9 months and 6 years of age that typically first manifested as difficulty walking (ataxia). Ophthalmic examination was sometimes limited by cognitive ability. Four of eight had exotropia, 7/7 bilateral supraduction defect, 5/7 poor convergence, 6/8 saccadic pursuit, 4/8 saccadic intrusions that resembled square-wave jerks, and 8/8 bilateral optic nerve head pallor. All patients lacked Bell phenomenon.
  
  
  CONCLUSIONS
  Upgaze palsy, although not a previously reported finding, was confirmed in all patients (except in one for whom assessment could not be performed) and thus can be considered part of the phenotype in children and young adults. Other frequent findings not previously highlighted were abnormal convergence, saccadic pursuit, and saccadic intrusions. Optic nerve head pallor and strabismus, previously reported findings in the disease, were found in 100% and 50% of our cohort, respectively, and the strabismus in our series was always exotropia. Taken together, these clinical findings may be helpful in distinguishing PLA2G6-related neurodegeneration from the other major cause of NBIA, recessive PANK2 mutations.
authors: Arif O
authors: AO
authors: Khan
authors: Abdulmajeed
authors: A
authors: AlDrees
authors: Salah A
authors: SA
authors: Elmalik
authors: Hamdy H
authors: HH
authors: Hassan
authors: Michel
authors: M
authors: Michel
authors: Giovanni
authors: G
authors: Stevanin
authors: Hamid
authors: H
authors: Azzedine
authors: Mustafa A
authors: MA
authors: Salih
mesh_terms: D000293:Adolescent; D000328:Adult; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics; D015331:Cohort Studies; D003241:Consanguinity; D005099:Exotropia / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D006801:Humans; D019189:Iron Metabolism Disorders / Q000175:diagnosis* / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D019150:Neuroaxonal Dystrophies / Q000175:diagnosis* / Q000235:genetics; D009887:Ophthalmoscopy; D011446:Prospective Studies; D012029:Refraction, Ocular / Q000502:physiology; D012438:Saccades; D055815:Young Adult
chemical_list: D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human