Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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May 9, 2016
Wolfram Syndrome (DIDMOAD)
- Background:
- Originally described by Wolfram in 1938, this rare genetic disorder (1 in 770,000) is inherited as an autosomal recessive trait with incomplete penetrance. Wolfram syndrome (WFS) is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER) stress-mediated cell death. The gene is expressed in pancreatic beta cells and neurons.
- Clinical Presentation:
- Early childhood in onset
- IDDM and vision loss are the first and essential features of WFS, followed by development of deafness, diabetes insipidus, and urinary tract abnormalities.
- Generally, cases having IDDM and optic atrophy together need to be evaluated with respect to WFS.
- Key Diagnostic Features:
- Typical MRI brain findings:
- Absence of T1 hyperintensisity normally recognized in posterior pituitary.
- Bilateral intraorbital and intracranial optic nerve atrophy.
- T2-hyperintense signal in the pons.
- Progressive brain stem atrophy, cerebellar atrophy, and later, generalized brain atrophy
- Genetic testing can be used to confirm WFS.
- Typical MRI brain findings:
- Differential Diagnosis:
- Autosomal dominant optic atrophy (ADOA): Cerebellar atrophy with superior vermian predominance, less prominent optic atrophy, and normal T1 pituitary bright spot
- Leber hereditary optic neuropathy: T2 signal abnormality of the intraorbital optic tracts, normal T1 pituitary bright spot
- Multiple system atrophy (MSA) and familial spinocerebellar degeneration: Pontocerebellar atrophy; pontine signal intensity changes, widely known as "cross signs"; normal optic nerves; and T1 pituitary bright spot
- Treatment:
- Although there are no current treatments for this disease, agents to treat ER stress-mediated apoptosis are currently in development. The life expectancy of patients diagnosed with this syndrome is about 30 years.
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