"...For example: the Beretta 21 is a bastardization of the original (and much smaller) 950 series guns. The 950 was .22short/.25. They were extremely reliable guns. The model 21 is an upsized version adapted for .22LR. Much of the reliability factor was lost in the LR version, and the .25 version is an afterthought..."-Bill DeShivs
I would hardly call the 21 a "bastardization". I owned three 950's back before the 21 was introduced, a 25, and two 22shorts (one of which had the longer barrel).
The 22short versions were reliable enough to be fun shooters, but not 100%. The 22short was noticeably less powerful than the LR (I once fired a HV 22 short into a ball shaped wax candle a little bigger than a softball...the impact started the ball rolling slowly, and the bullet moved slow enough to leave a curved track...it barely made it all the way through, bouncing off a paperback book behind it).
A well designed 22pistol is extremely reliable, feeding the LR cartridge with no issues. My four 22 pistols include the Bobcat, the Ruger SR22 and 1978 standard model, and a 1960's French Unique. All four are 100% reliable. Even the Unique, which was missing its extractor when I bought it for a song, works perfectly.
No, the reliability factor in 22 pistols is buying good ammo.
Still waiting for my Flashback...I would like it now, please.