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Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review

Wolfram syndrome is a neurodegenerative disorder caused by pathogenic variants in the genes WFS1 or CISD2. Clinically, the classic phenotype is composed of optic atrophy, diabetes mellitus type 1, diabetes insipidus, and deafness. Wolfram syndrome, however, is phenotypically heterogenous with variab...

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Autores principales: Jauregui, Ruben, Abreu, Nicolas J., Golan, Shani, Panarelli, Joseph F., Sigireddi, Meenakshi, Nayak, Gopi K., Gold, Doria M., Rucker, Janet C., Galetta, Steven L., Grossman, Scott N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376978/
https://www.ncbi.nlm.nih.gov/pubmed/37508961
http://dx.doi.org/10.3390/brainsci13071030
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author Jauregui, Ruben
Abreu, Nicolas J.
Golan, Shani
Panarelli, Joseph F.
Sigireddi, Meenakshi
Nayak, Gopi K.
Gold, Doria M.
Rucker, Janet C.
Galetta, Steven L.
Grossman, Scott N.
author_facet Jauregui, Ruben
Abreu, Nicolas J.
Golan, Shani
Panarelli, Joseph F.
Sigireddi, Meenakshi
Nayak, Gopi K.
Gold, Doria M.
Rucker, Janet C.
Galetta, Steven L.
Grossman, Scott N.
author_sort Jauregui, Ruben
collection PubMed
description Wolfram syndrome is a neurodegenerative disorder caused by pathogenic variants in the genes WFS1 or CISD2. Clinically, the classic phenotype is composed of optic atrophy, diabetes mellitus type 1, diabetes insipidus, and deafness. Wolfram syndrome, however, is phenotypically heterogenous with variable clinical manifestations and age of onset. We describe four cases of genetically confirmed Wolfram syndrome with variable presentations, including acute-on-chronic vision loss, dyschromatopsia, and tonic pupils. All patients had optic atrophy, only three had diabetes, and none exhibited the classic Wolfram phenotype. MRI revealed a varying degree of the classical features associated with the syndrome, including optic nerve, cerebellar, and brainstem atrophy. The cohort’s genotype and presentation supported the reported phenotype–genotype correlations for Wolfram, where missense variants lead to milder, later-onset presentation of the Wolfram syndrome spectrum. When early onset optic atrophy and/or diabetes mellitus are present in a patient, a diagnosis of Wolfram syndrome should be considered, as early diagnosis is crucial for the appropriate referrals and management of the associated conditions. Nevertheless, the condition should also be considered in otherwise unexplained, later-onset optic atrophy, given the phenotypic spectrum.
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spelling pubmed-103769782023-07-29 Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review Jauregui, Ruben Abreu, Nicolas J. Golan, Shani Panarelli, Joseph F. Sigireddi, Meenakshi Nayak, Gopi K. Gold, Doria M. Rucker, Janet C. Galetta, Steven L. Grossman, Scott N. Brain Sci Case Report Wolfram syndrome is a neurodegenerative disorder caused by pathogenic variants in the genes WFS1 or CISD2. Clinically, the classic phenotype is composed of optic atrophy, diabetes mellitus type 1, diabetes insipidus, and deafness. Wolfram syndrome, however, is phenotypically heterogenous with variable clinical manifestations and age of onset. We describe four cases of genetically confirmed Wolfram syndrome with variable presentations, including acute-on-chronic vision loss, dyschromatopsia, and tonic pupils. All patients had optic atrophy, only three had diabetes, and none exhibited the classic Wolfram phenotype. MRI revealed a varying degree of the classical features associated with the syndrome, including optic nerve, cerebellar, and brainstem atrophy. The cohort’s genotype and presentation supported the reported phenotype–genotype correlations for Wolfram, where missense variants lead to milder, later-onset presentation of the Wolfram syndrome spectrum. When early onset optic atrophy and/or diabetes mellitus are present in a patient, a diagnosis of Wolfram syndrome should be considered, as early diagnosis is crucial for the appropriate referrals and management of the associated conditions. Nevertheless, the condition should also be considered in otherwise unexplained, later-onset optic atrophy, given the phenotypic spectrum. MDPI 2023-07-05 /pmc/articles/PMC10376978/ /pubmed/37508961 http://dx.doi.org/10.3390/brainsci13071030 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Jauregui, Ruben
Abreu, Nicolas J.
Golan, Shani
Panarelli, Joseph F.
Sigireddi, Meenakshi
Nayak, Gopi K.
Gold, Doria M.
Rucker, Janet C.
Galetta, Steven L.
Grossman, Scott N.
Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review
title Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review
title_full Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review
title_fullStr Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review
title_full_unstemmed Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review
title_short Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review
title_sort neuro-ophthalmologic variability in presentation of genetically confirmed wolfram syndrome: a case series and review
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376978/
https://www.ncbi.nlm.nih.gov/pubmed/37508961
http://dx.doi.org/10.3390/brainsci13071030
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