FALS but no other cases in family

[Optimist333]

Hi, my mother was recently diagnosed with FALS, the genetic testing came back saying it was in fact genetic. This confuses me as there have been no other cases of als or anything other than heart issues in my family. When researching I came across an article that stated if the als was genetic it most likely will show up in every generation unless you were the 50% chance you did not copy the defective gene (c9) then you break the link for your children to inherit. My main question is how can it be genetic if there haven't been any other cases in my family. I have children and I have siblings with children, so my anxieties have been heavy lately.

 

[Nikki J]

C9 is very complicated. Initially after it was discovered in 2011 it was believed to be always highly penetrant because the families studied had multiple cases generation after generation. My family is like this. Over time we have found there are also families like yours where it shows up suddenly in one person. At first they thought the mutation just happened in that person and their family would subsequently become like mine but they now know it has usually been there right along and just didn’t manifest before.

They now are telling c9 carriers that they need to look at their own family history to see how likely it is they will develop ALS. A family like mine with multiple members affected over multiple generations would have a high risk. A family like yours a much lower risk. There is a recent paper with a mathematical model of personalized risk

Each of your mother’s children have a 50% chance of being a carrier. If they are not their children can not inherit it. If they are they are still unlikely to get sick given your family history.

If you want to be technically correct she has genetic ALS ( GALS) rather than FALS as FALS is defined as having multiple cases in first and or second degree relatives with or without a confirmed mutation. I hope it never becomes true FALS.

Finally genetic treatments and even prevention and cure are coming. My neurologist estimates within 10-20 years maximum