TY - JOUR
T1 - Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome
T2 - A Case Series and Review
AU - Jauregui, Ruben
AU - Abreu, Nicolas J.
AU - Golan, Shani
AU - Panarelli, Joseph F.
AU - Sigireddi, Meenakshi
AU - Nayak, Gopi K.
AU - Gold, Doria M.
AU - Rucker, Janet C.
AU - Galetta, Steven L.
AU - Grossman, Scott N.
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/7
Y1 - 2023/7
N2 - 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.
AB - 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.
KW - Wolfram syndrome
KW - autosomal recessive
KW - diabetes mellitus
KW - genotype–phenotype correlation
KW - neuro-ophthalmology
KW - neurogenetics
KW - optic atrophy
UR - http://www.scopus.com/inward/record.url?scp=85166659522&partnerID=8YFLogxK
U2 - 10.3390/brainsci13071030
DO - 10.3390/brainsci13071030
M3 - Article
AN - SCOPUS:85166659522
SN - 2076-3425
VL - 13
JO - Brain Sciences
JF - Brain Sciences
IS - 7
M1 - 1030
ER -