Abstract
Wolfram syndrome (WFS) is a rare autosomal recessive neurodegenerative disease whose diagnosis requires diabetes mellitus and optic atrophy (OA). WFS includes a wide spectrum of other possible complications such as diabetes insipidus, sensorineural deafness, urinary tract problems, neurological and psychiatric disorders. Most WFS patients show type 1 syndrome (WFS1) caused by mutations in the WFS1 gene, encoding Wolframin protein, while few patients are affected by WFS type 2 (WFS2) due to a pathogenetic variants in the CISD2 gene encoding an endoplasmic reticulum intermembrane small protein. WFS2 is considered a phenotypic and genotypic variant of WFS, from which differs only for the increased risk of bleeding and presence of peptic ulcers. OA and diabetes are considered cardinal features of WFS. We hereby report the ophthalmologic evaluation in a patient, previously described, with WFS2 after 8 years of follow-up. A 20-year-old white woman was referred to our retinal center for the first time in 2012 following a diagnosis of a novel intragenic exon 2 CISD2 homozygous deletion, for the suspicion of an associated bilateral OA. Fundus examination, spectral-domain optical coherence tomography, visual field, visual evoked potentials were performed and confirmed the presence of an optic neuropathy that remained stable over 8 years follow up. A slowly progressive optic neuropathy, rather than OA can characterize patients with WFS2 and CISD2 intragenic deletion.
Highlights
Wolfram syndrome (WFS) is a rare autosomal recessive neurodegenerative disease characterized by a wide phenotypic spectrum including non-autoimmune diabetes mellitus (DM) (1), and optic atrophy (OA), often associated with diabetes insipidus (DI) and deafness, the historical acronym: DIDMOAD (2)
To the best of our knowledge, this is the longest follow-up in the literature in a patient with WFS type 2 (WFS2) and CISD2 intragenic deletion
In this report we show that WFS2 can be characterized by an optic neuropathy rather than an OA, with a very slow progression over the time
Summary
CASE PRESENTATIONWolfram syndrome (WFS) is a rare autosomal recessive neurodegenerative disease characterized by a wide phenotypic spectrum including non-autoimmune diabetes mellitus (DM) (1), and optic atrophy (OA), often associated with diabetes insipidus (DI) and deafness, the historical acronym: DIDMOAD (2). Other common clinical signs include urinary tract problems and renal dysfunction, related to neurogenic bladder, endocrine disorders, severe gastrointestinal ulcers, psychiatric symptoms, and progressive neurological degeneration (2). Our group reported the first Italian Caucasian girl with WFS2 (7), carrying a novel intragenic exon 2 CISD2 homozygous deletion from C-4OKFJ (102,885,416 bp) to C-6MGSK (102,886,154 bp), mapping on chromosome 4q24, showing optic neuropathy rather than OA, and impaired platelet aggregation to adenosine diphosphate and not to collagen, as described in the Jordanian family (5).
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