If I-485 gets denied, your wife likely get 3 or even 10 year bar on coming back to the US.
With overstay, the safest thing is to not travel internationally at all until Green Card is in hand. Nowadays, USCIS is aware whether somebody left the country, and the AOS decision (denial for example) may be "conveniently" issued while she's overseas.
You both seem to take immigration lightly. I'd be doing everything to submit response to RFE ASAP. As others mentioned above, she should try going to a clinic and complete the medical exam before leaving the US. There's no extension for RFE as far as I know.
She'll probably have the bar too.