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

Wolfram-like syndrome (WFLS) is a recently described autosomal dominant disorder with phenotypic similarities to autosomal recessive Wolfram syndrome (WS), including optic at-rophy, 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, EM-BACE, and Cochrane Library. We included studies reporting patients with a clinical picture consisting at least 2 typical clinical manifestations of WSF1 disorders and heterozygous mu-tations in WFS1. In total, 86 patients from 35 studies were included. The most common phe-notype 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 impair-ment 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 in-herited 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.& COPY; 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/)

Automated summary

Wolfram-like syndrome (WFLS) is an autosomal dominant disorder that shares similar phenotypic features with autosomal recessive Wolfram syndrome (WS), including optic atrophy, hearing impairment, and diabetes mellitus. This review summarizes current literature, identifies the clinical characteristics, and explores the potential genotype-phenotype correlations. The findings suggest that WFLS has a relatively milder phenotype compared to WS, with optic atrophy and hearing impairment being the most common manifestations. Diabetes mellitus and cataract can also occur in a significant proportion of patients. The specific mutations in the WFS1 gene are associated with the age at onset and severity of the clinical manifestations. Rating: 8 out of 10.