If anyone would be able to shed some light to what most likely occurred, that would be amazing. My Czech grandfather remembers being sick in bed with the measles at 8yo in about 1941, possibly in Brno. His mother was dragged out of the house and disappeared for 2 years. He has absolutely no idea why. He says she was a loving affectionate mother but she was cold and generally a completely different person when she returned. His father had already 'disappeared' only to return years later, not sure why either. His mother was German and his father Czech and I believe his father may have been the mayor of the town at the time. He rambles and mind all over the place so it's hard to pin point exact details. Any ideas?
A lot of this depends on the definition of "about 1941". If you can independently verify both your grandfathers birth date (probably not too hard with primary documentary evidence, but it's possible that it's unclear) and the date of his infection with measles (probably fairly difficult), then you can make some informed guesses as to where to look next:
If this happened before 1945, then as others have mentioned, the Holocaust Survivors and Victims database may give you a sense of why and where she went. If her ethnically Czech husband was the mayor of the town they lived in, it's possible that he was arrested by the Nazis as a hostage or political prisoner and spent time in a concentration camp or prison, explaining his disappearance for a period of time and later return (probably in 1945 at the liberation).
If your grandfather is a little out about the date, and this happened after 1945, the Czech government began in 1945 to expel the majority of ethnic Germans from Czechoslovakia. While nearly 2.5 million ethnic Germans were expelled to the territory of what is now the Federal Republic, 250,000 to 300,000 did stay behind, and there were internment camps for ethnic Germans as well. So it's entirely possible that your great-grandmother was one of the Germans that stayed behind - there were specific exemptions for "anti-fascists", so it's quite possible that if your great-grandfather was jailed by the Nazis, that may have led to your great-grandmother being arrested and interned, but subsequently released as an anti-fascist German.
Documentary evidence will be relatively hard to come by, but try to find out if your family has any more details around dates or any papers from the time tucked away somewhere. Your username implies your Australian, so it may help to understand when your family came to Australia. If it was immediately after the war (1945-1948, say), they may have been expelled. If it was after 1948, it may have been because your great-grandparents left after the communist coup.
I'm aware this answer is fairly conjectural, but hopefully still within the rules, given the nature of the question.
You can search the Holocaust Survivors and Victims Database for your grandmother to see if she was held at a concentration camp. I have ethnically German Czech relatives who were held at Dachau for a year or more in the protective custody of the SS, which generally meant they were seen as subversive to the regime in some way.
Do you have any relatives still living there that could know what happened? Or maybe they have inherited documents or letters written at the time.
If not, I think your best bet would be to look for local history books focused on the Second World War. If your great grandfather was the mayor it’s definitely something that is documented and there are probably city hall’s documents about what happened to him.
Brno is a big city and there are historical archives to check as well if they moved the documents from city hall for conservation’s purposes.
If they were from Brno you try to find your great-grandfather/mothers name here. here. It is a list of important people from Brno. Unfortunately it¨'s only in Czech.
Write the name to the field "ve jménech" and press the button "Vyhledat".
Brno is the second biggest town in the Czech Republic, so if your great-grandfather was a mayor, he would be a fairly important political figure.
The 13th Mayor of Brno was called Karel Tomeš, he was a fighter during WW1 as a czechoslovak legionare and died in a concentration camp. His tenure was from 31. 12. 1925 – 2. 12. 1935. His wife was called Bohumila and she was of czech descent.
The 14th mayor was called Ing. Dr. Rudolf Spazier, who contributed to the city's canalization system and was an university teacher. He was jailed by Germans during occupation of Czechoslovakia till the end of the war. I did some digging and his wife was of czech nationality, named Maria Šafaříková (maiden name), so I don't think that was your greatgrandfather? His tenure was 2. 12. 1935 – 23. 3. 1939
The next mayor was Oskar Judex, who was apointed by NSDAP and jailed after the war.
Sources: Internet Encyclopedy of City Brno - https://encyklopedie.brna.cz/home-mmb/
You can also check the Vital Records of City of Brno, which are scanned and acessible online, to see if you can spot the names of your great-grandparents. Generally, births, deaths and marriages are noted there.
If your grandfather was 8 year old at 1941, he would be born at around 1933, so for this year: https://www.mza.cz/actapublica/matrika/detail/10274?image=216000010-000253-003381-000000-017879-000000-VR-B08472-00010.jp2
You can also try to contact Brno's Department of History at Masaryk University. https://historie.phil.muni.cz/en