Delineating Wolfram-like syndrome: A systematic review and discussion of the WFS1-associated disease spectrum

Cansu de Muijnck, Jacoline B.ten Brink, Arthur A. Bergen, Camiel J.F. Boon, Maria M. van Genderen*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Wolfram-like syndrome (WFLS) is a recently described autosomal dominant disorder with phenotypic similarities to autosomal recessive Wolfram syndrome (WS), including optic atrophy, hearing impairment, and diabetes mellitus. We summarize current literature, define the clinical characteristics, and investigate potential genotype phenotype correlations. A systematic literature search was conducted in electronic databases Pubmed/MEDLINE, EMBACE, and Cochrane Library. We included studies reporting patients with a clinical picture consisting at least 2 typical clinical manifestations of WSF1 disorders and heterozygous mutations in WFS1. In total, 86 patients from 35 studies were included. The most common phenotype consisted of the combination of optic atrophy (87%) and hearing impairment (94%). Diabetes mellitus was seen in 44% of the patients. Nineteen percent developed cataract. Patients with missense mutations in WFS1 had a lower number of clinical manifestations, less chance of developing diabetes insipidus, but a younger age at onset of hearing impairment compared to patients with nonsense mutations or deletions causing frameshift. There were no studies reporting decreased life expectancy. This review shows that, within the spectrum of WFS1-associated disorders or “wolframinopathies,” autosomal dominantly inherited WFLS has a relatively mild phenotype compared to autosomal recessive WS. The clinical manifestations and their age at onset are associated with the specific underlying mutations in the WFS1 gene.

Original languageEnglish
Pages (from-to)641-654
Number of pages14
JournalSurvey of ophthalmology
Issue number4
Publication statusPublished - 1 Jul 2023


  • Autosomal dominant
  • Hereditary optic neuropathy
  • Optic atrophy
  • WFS1
  • Wolfram-like syndrome


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