For context, you can find Part 1 here: https://wolframsyndrome.wustl.edu/uncovering-a-milder-wolfram-syndrome-variant-in-jewish-populations-part-1/
As I described in Part 1, our research has identified a milder variant of Wolfram syndrome predominantly observed in Jewish populations, particularly among individuals of Ashkenazi Jewish descent. But what exactly do I mean by “mild”? This term refers to a delayed onset of diabetes and optic nerve atrophy compared to the classic form of Wolfram syndrome. Furthermore, individuals with this milder variant often do not exhibit the full spectrum of cardinal features typically associated with Wolfram syndrome.
The hallmark features of classic Wolfram syndrome include early-onset diabetes mellitus, optic nerve atrophy, hearing loss, arginine vasopressin deficiency (central diabetes insipidus), neurogenic bladder, anxiety or depression, and neurodegeneration characterized by cerebellar and brainstem atrophy. For a detailed comparison, see the table published by our team in the Journal of Clinical Investigation Insight: https://insight.jci.org/articles/view/156549/table/1
While it is possible that individuals with this milder variant could develop more of these symptoms as they age, additional data is needed for me to understand their progression. This underscores the importance of engaging Jewish families and the medical community in identifying and studying these cases.
The challenge, however, is significant. Wolfram syndrome itself is an extremely rare genetic disorder that many doctors—and understandably, most patients—are unfamiliar with. This makes detecting and diagnosing patients with a milder variant even more difficult.
There are certain clues that may help doctors and patients recognize this variant. One such indicator is atypical diabetes, which I will explore further in my next blog post.
Your support in spreading awareness and helping us gather more data is crucial as we continue this research. Stay tuned for the next blog.
Fumihiko (Fumi) URANO, MD, PhD
Samuel E. Schechter Professor of Medicine
Director, Wolfram syndrome and related disorders clinic and study
Washington University Medical Center