Some approaches to diagnosis such as Large Language Models consider findings to be present or absent in diseases, with inadequate information about the timing of their disappearance or age of onset.
Example to work through (showing disappearance)
Consider a 10-year-old girl with developmental delay and some morphological abnormalities. A disease to consider is Smith-Magenis syndrome: (Registered users can click the images below to jump into the software; some videos may be helpful in navigating from there)
Hypotonia is a feature in all patients with this syndrome, as shown on the Explain Disease screen, accessed from the top black navigation bar by clicking on the blue X when a disease is active (highlighted). This is seen in the image below, where the frequency bar for hypotonia extends close to 100%. But infantile hypotonia goes away within a few years after birth, as shown by the orange coloration of the bulk of the frequency bar. The absence of hypotonia in a 10-year-old doesn’t weigh against the diagnosis of Smith-Magenis syndrome because hypotonia would likely be gone.
Another situation in which the details about time matter is when onset of a finding is later than the age of the patient.
Example to work through (showing onset later)
Consider an 8-month-old boy with recent onset of kyphosis. Two diseases to consider are Achondroplasia and MPS1-H (Hurler syndrome). In these diseases, all the patients are short, but this patient isn’t short. One might imagine that both diseases will move far lower in the differential diagnosis. (Registered users can click the images below to jump into the software; some videos may be helpful in navigating from there)
Adding the absence of short stature pushes Achondroplasia off the differential diagnosis, but MPS1 moves to the top.
The reason is that although short stature is universal in MPS1-H, it is rarely present at 8 months of age. This is shown on the Explain Disease screen, accessed from the top black navigation bar by clicking on the blue X when a disease is active (highlighted). The later onset is represented as the purple part of the frequency bar next to short stature in the figure below.
The age of onset and disappearance of a finding is of particular importance in pediatrics.
Neglecting such time information would lead to diagnostic errors when interpreting absence of findings that develop later or have already gone away.
This page is part of a series on the Elements of Diagnosis.
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