Some X-linked dominant disorders, for the sake of calling them X-linked dominant disorders, classically
you will need to know for sure Fragile-X syndrome. Now, I’m not going to go into detail on Fragile-X
syndrome in this lecture because it’s a triplet expanding repeat. I’m going to cover that in the next lecture.
X-linked dominant though, Fragile-X, definitely you need to know that one. Hypophosphatemic rickets is another
one that you should know along with Rett syndrome. Again, Rett syndrome is only showing up in females.
Another key that you really should be aware of with Rett syndrome is it looks like some other disorders.
It looks quite a lot like Angelman syndrome so it can often be misdiagnosed as Angelman syndrome.
It used to be considered one of the autism spectrum disorders. Since the allele was located for these specific
characteristics that show up in Rett syndrome including the scoliosis and such neurodegeneration,
it has been removed from autism spectrum. But there’s certainly a degree of mental retardation
that goes on in there and some classic movements like hands going to the mouth and wringing of the hands
that let it stand out from those other disorders. These are three that you should certainly keep in mind
when we’re considering X-linked dominant disorders. We’ve covered a lot of different inheritance patterns.
Sometimes figuring them all out can be a little bit difficult especially with the complexities of penetrance
and expressivity and lethality and manifesting heterozygotes and all of those things. Speaking of which,
why don’t you just take a moment and write down all the exceptions to normal inheritance patterns
that you can recall. Now, coming back to the normal inheritance patterns, here we’ll take a look at a flow chart.
I put this together because I think it’s quite helpful. Let’s say you have affected individuals
having an affected parent versus not having an affected parent. That’s really the point that you want to start.
If they do have an affected parent, that means it’s transmitted generation to generation. Thus, it's most likely
to be a dominant trait. Now, does it have male to male transmission? Now, we covered some exceptions.
But in general, does it have male to male transmission? If your answer is yes, then it is probably
autosomal dominant because in X-linked, the male is going to give his son a Y and it wouldn’t pass any X-linked.
But we have exceptions to all rules. If it is not male to male transmitted, it is probably an X-linked dominant
trait unless there’s an exception. All daughters of the affected male are also affected? If the answer is no,
then we have to go back up to it being an autosomal dominant. This last bracket helps you sort out
whether it’s autosomal or X-linked in the dominant case. Now, if the answer is yes, then we know
it’s an X-linked dominant. If all daughters of an affected male are also affected, then it’s definitely X-linked dominant.
Now, what about though if we do not have an affected parent with the individuals? The answer is no.
Then we go over into a whole class of recessive options. Now, we need to know is it X-linked or is it autosomal.
Take a moment and think, what is the split. That might tell us if it’s X-linked or autosomal? The question here is
are all the males affected or almost all because there are always exceptions, right? If they are,
then it’s an X-linked recessive disorder. If they are not, then we’re looking at an autosomal recessive disorder.
Hopefully, this flow chart is useful in helping you separate disorders. As you take your exams,
they will often tell you the inheritance patterns. Who has it? Who doesn't? So, perhaps you can sort it out
rather than just memorizing by the symptoms that they give you if you keep this chart in mind.
If you can write before you wrap up your thoughts about this lecture, spend a moment and summarize this chart.
See if you can jot down the yes’s and no’s and make that a mind map for yourself to keep in line for your exams.
Thanks so much for listening. I look forward to seeing you in the next lecture.