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Visual pathway function and structure in Wolfram syndrome: patient age, variation and progression
  1. James Hoekel1,
  2. Anagha Narayanan2,
  3. Jerrel Rutlin2,
  4. Heather Lugar2,
  5. Amal Al-Lozi2,
  6. Tamara Hershey2,3,4,
  7. Lawrence Tychsen1,5
  1. 1 Department of Ophthalmology, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis, Missouri, USA
  2. 2 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
  3. 3 Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA
  4. 4 Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA
  5. 5 Department of Pediatrics, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis, Missouri, USA
  1. Correspondence to Dr Lawrence Tychsen; tychsen{at}


Background/aims To report alterations in visual acuity and visual pathway structure over an interval of 1–3 years in a cohort of children, adolescents and young adults who have Wolfram syndrome (WFS) and to describe the range of disease severity evident in patients with WFS whose ages differed by as much as 20 years at first examination.

Methods Annual, prospective ophthalmological examinations were performed in conjunction with retinal nerve fibre layer (RNFL) analysis. Diffusion tensor MRI-derived fractional anisotropy was used to assess the microstructural integrity of the optic radiations (OR FA).

Results Mean age of the 23 patients with WFS in the study was 13.8 years (range 5–25 years). Mean log minimum angle resolution visual acuity was 0.66 (20/91). RNFL thickness was subnormal in even the youngest patients with WFS. Average RNFL thickness in patients with WFS was 57±8 µ or ~40% thinner than that measured in normal (94±10 µ) children and adolescents (P<0.01). Lower OR FA correlated with worse visual acuity (P=0.006). Subsequent examinations showed declines (P<0.05) in visual acuity, RNFL thickness and OR FA at follow-up intervals of 12–36 months. However, a wide range of disease severity was evident across ages: some of the youngest patients at their first examination had deficits more severe than the oldest patients.

Conclusion The genetic mutation of WFS causes damage to both pregeniculate and postgeniculate regions of the visual pathway. The damage is progressive. The decline in visual pathway structure is accompanied by declines of visual function. Disease severity differs widely in individual patients and cannot be predicted from their age.

  • child health (paediatrics)
  • genetics
  • optic nerve
  • visual (cerebral) cortex
  • visual pathway
  • cosmesis

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  • Contributors JH designed and executed the ophthalmological work, including interpretation and analysis. LT designed, analysed, interpreted, wrote and revised the manuscript; he is responsible for overall content. TH designed the parent study on Wolfram syndrome (HD070855), directed the neuroimaging data collection, analysis and interpretation and assisted in manuscript writing. AN prepared and analysed data used in this manuscript. AA-L assisted in data analysis and manuscript planning. HL and JR designed, analysed and interpreted the neuroimaging data.

  • Funding This work was supported by the NICHD (HD070855; Hershey, PI) and supported by CTSA (UL1 RR024992) and Diabetes Research Center (DK 020579), the Jack and JT Snow Foundation, American Diabetes Association (Permutt/Urano), the George Decker and Julio V Santiago Pediatric Diabetes Research Fund.

  • Competing interests None declared.

  • Ethics approval The study was approved by the Institutional Review Board of Washington University in St. Louis.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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