The presence of two pathogenic variants in the WFS1 gene leads to the occurrence of a rare genetic disease in children – Wolfram syndrome (WFS), which includes insulin-dependent diabetes mellitus (DM), optic atrophy (OA), diabetes insipidus (DI), and deafness (D). However, the presence of a single mutation in the WFS1 gene results in a number of other autosomal dominant inherited diseases, including Wolfram-like syndrome (WFS-like).
A 10-year-old boy was referred to the Genetic Outpatient Clinic with suspected WFS based on the coexistence of D, type 1 DM, short stature, and abnormalities in ophthalmologic examination (astigmatism and OA due to the optical coherence tomography result). The genetic analysis did not confirm WFS syndrome in the boy but identified a single likely pathogenic de novo variant in the WFS1 gene, which confirmed WFS-like syndrome.
Currently, the patient is under the care of an endocrinologist, diabetologist, ophthalmologist, audiologist, and also psychologist because of mood disorders.
Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from the parents of a patient included in this study.
Ethical approval: Not applicable.
1. Fonseca, SG, Ishigaki, S, Oslowski, CM, Lu, S, Lipson, KL, Ghosh, R, et al.. Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells. J Clin Invest 2010;120:744–55. https://doi.org/10.1172/jci39678. Search in Google Scholar
2. Tranebjærg, L, Barrett, T, Rendtorff, ND. WFS1 Wolfram syndrome spectrum disorder. In: Adam, MP, Ardinger, HH, Pagon, RA, Wallace, SE, Bean, LJH, Mirzaa, G, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2009:1993–2021 pp. Search in Google Scholar
3. Kumar, S. Wolfram syndrome: important implications for pediatricians and pediatric endocrinologists. Pediatr Diabetes 2010;11:28–37. https://doi.org/10.1111/j.1399-5448.2009.00518.x. Search in Google Scholar
4. De Franco, E, Flanagan, SE, Yagi, T, Abreu, D, Mahadevan, J, Johnson, MB, et al.. Dominant ER stress-inducing WFS1 mutations underlie a genetic syndrome of neonatal/infancy-onset diabetes, congenital sensorineural deafness, and congenital cataracts. Diabetes 2017;66:2044–53. https://doi.org/10.2337/db16-1296. Search in Google Scholar
5. Lusk, L, Black, E, Vengoechea, J. Segregation of two variants suggests the presence of autosomal dominant and recessive forms of WFS1-related disease within the same family: expanding the phenotypic spectrum of Wolfram Syndrome. J Med Genet 2020;57:121–3. https://doi.org/10.1136/jmedgenet-2018-105782. Search in Google Scholar
6. Eiberg, H, Hansen, L, Kjer, B, Hansen, T, Pedersen, O, Bille, M, et al.. Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene. J Med Genet 2006;43:435–40. https://doi.org/10.1136/jmg.2005.034892. Search in Google Scholar
7. Valéro, R, Bannwarth, S, Roman, S, Paquis-Flucklinger, V, Vialettes, B. Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene. Diabet Med 2008;25:657–61. https://doi.org/10.1111/j.1464-5491.2008.02448.x. Search in Google Scholar
8. Soliman, AT, Bappal, B, Darwish, A, Rajab, A, Asfour, M. Growth hormone deficiency and empty sella in DIDMOAD syndrome: an endocrine study. Arch Dis Child 1995;73:251–3. https://doi.org/10.1136/adc.73.3.251. Search in Google Scholar
9. Papadimitriou, A, Fountzoula, I, Grigoriadou, D, Christianakis, S, Tzortzatou, G. Testicular descent related to growth hormone treatment. J Pediatr Endocrinol Metab 2003;16:561–3. https://doi.org/10.1515/jpem.2003.16.4.561. Search in Google Scholar
10. Rendtorff, ND, Lodahl, M, Boulahbel, H, Johansen, IR, Pandya, A, Welch, KO, et al.. Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment. Am J Med Genet 2011;155A:1298–313. https://doi.org/10.1002/ajmg.a.33970. Search in Google Scholar
11. Tessa, A, Carbone, I, Matteoli, MC, Bruno, C, Patrono, C, Patera, IP, et al.. Identification of novel WFS1 mutations in Italian children with Wolfram syndrome. Hum Mutat 2001;17:348–9. https://doi.org/10.1002/humu.32. Search in Google Scholar
12. Reschke, F, Rohayem, J, Maffei, P, Dassie, F, Schwandt, A, de Beaufort, C, et al.. Collaboration for rare diabetes: understanding new treatment options for Wolfram syndrome. Endocrine 2021;71:626–33. https://doi.org/10.1007/s12020-021-02622-3. Search in Google Scholar
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