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Ophthalmic features of PLA2G6-related paediatric neurodegeneration with brain iron accumulation
  1. Arif O Khan1,
  2. Abdulmajeed AlDrees2,
  3. Salah A Elmalik2,
  4. Hamdy H Hassan3,
  5. Michel Koenig4,
  6. Giovanni Stevanin5,6,
  7. Hamid Azzedine7,
  8. Mustafa A Salih8
  1. 1Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
  2. 2Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  3. 3Department of Radiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  4. 4Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS/INSERM/Université de Strasbourg, et Collège de France, Illkirch, France
  5. 5Neurogenetics team, école pratique des etudes-hesam université, Paris, France
  6. 6Sorbonne universités, u1127, umr7225, INSERM, CNRS, UPMC, Institut du Cerveau et de la Molle, Paris, France
  7. 7Department of Medical Genetics, Faculty of Biology and Medicine, CHUV-University of Lausanne, Lausanne, Switzerland
  8. 8Division of Pediatric Neurology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  1. Correspondence to Dr Arif O Khan, Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia; arif.khan{at}


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.

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