In this lecture, we will discuss Trisomy 21 or Down syndrome.
Trisomy 21 is when a patient has 3 copies of their 21st chromosome
in every cell in their body.
These patients have characteristic facial features like you can see here.
They have hypotonia, they have intellectual disability
and they may have congenital malformations
and we?ll go through of this more carefully in this lecture.
So how is this happened?
The most common times about 94% at a time, this is from non-disjunction.
Basically, one parent creates two normal gametes
and the other parent creates one gamete with two copies
and the other one simply isn?t viable.
Then through freak occurrence, the gametes with two copies
fertilizes a normal egg or the egg has two copies
and is fertilize by a normal sperm
and this results in a patient with 3 copies of the 21st chromosome.
So, this is non-disjunction, this is about 94% at a time.
About 6% of a time this will happen through Robertsonian translocation.
Robertsonian translocation is a little bit complicated
so I wanna walk you through at this one time
so we are all in the same page.
We?ll repeat Robertsonian translocation when we talk about other trisomies.
But here we have a patient who is normal
and a spouse who has a Robertsonian translocation,
this spouse is completely normal from the standpoint
of how they appear to you or how they interact with you.
This patient has two blue chromosomes 14, I just chose 14 as an example.
Then for chromosome 21, a piece of it has been translocated
onto the end of one of those 14 chromosomes.
So, they have the appropriate amount of chromosomal material in each cell,
it?s just mislocated with half of one chromosome being adhered to another.
That?s the Robertsonian translocation,
but now let?s watch what happened when a patient
who has translocation then goes and has a child with a normal individual
and what happens to the various opportunities for their offspring.
So, let?s consider a case where a parent who has a normal genome
is going to have a baby with a parent who has a Robertsonian translocation.
The normal parent will make two gametes, these will both be normal.
One copy of 21 which are the red ones
and one copy of 14 which are the blue ones.
However, the parent who has translocation carrier
will make 6 possible gametes
and you can see them all drawn here with the lowest one being a normal gamete,
but the others all being variations.
Now, when this two parents make an offspring,
it?s possible that they may make a normal offspring
as you can see in this picture with the lowest gamete
and a translocated carrier matching up
with one of the normal gametes from the normal patient.
However, they may also make Trisomy 14 that?s not viable.
That child will not come to be
or they could create yet another translocation carrier
like the translocation carrier in the first example.
This child will grow to be a carrier of Down syndrome,
but will not have any manifestation of Down syndrome
or they could make a monosomy 21, which is not viable.
This child will not become a being
or alternatively, they could create a translocation
such that this patient has Down syndrome.
They have essentially 3 copies of the 21st chromosome,
one of them is adhered to there 14th chromosome
or alternatively, they could create monosomy 14 that?s not viable either.
So essentially, the odds are for this couple
that they can either have a normal child.
A child who is put at risks for creating children in the next generation
in a similar way or a child with Down syndrome.
So, let?s look now at risks for Down syndrome.
The biggest risk that we have to consider
is the maternal age with women who get older.
As they get older, it?s more and more likely for them to create eggs
that have an extra copy of a 21st chromosomes
and you can see the risks here.
So generally, we consider 35, a point at which the risk starts to really come up
and after 40 it comes up dramatically and those are the risks as you can see.
So, let?s say we have a baby
and we're wondering whether they might have Down syndrome.
This is a diagnosis that frequently made on physical exam
and there are some classic physical exam findings that we can see.
One is they can have epicanthal folds or upslanting fissures of their eyes.
They may have midface hypoplasia, you can see that a little bit in this child.
They may have brachycephaly,
they may have a little bit of excessive skin behind the neck,
sometimes we can see that in utero on ultrasound.
You may see something called a palmar crease,
this is where that crease goes straight across the hand
instead of branching like it normally does.
You may see a slight gap between the first and second toes
much like a flip flop sandal, it's where that flip flop post would go
and you may see that gap there
and you can see small white spots in the iris
which are called Brushfield spots that can be associated with Down syndrome.
Patients with Down syndrome have other issues
that can be more consequential,
one examples congenital heart disease
and this can show up at as many as 50% of patients,
and the most common is what we called an endocardial cushion defect
which is also called the common AV canal.
This is when they have both of VSD and ASD
essentially creating one large chamber in the heart.
Patients with Down syndrome
are increased risk for duodenal atresia about 12% at a time.
As you can see here we?ll have that classic finding of the double bubble sign
on abdominal x-ray very early in life that represents quite quickly
with inability to eat and inability to defecate
and you can see that double bubble area
where one bubble is in the stomach
and the other bubble is the query of air before that area of duodenal atresia.
Patients may develop congenital hypothyroidism,
this hopefully will be picked up on the new born screen.
If not, we want to address it as quickly as possible.
These infants happen to have it by 1% at a time
among patients with Down syndrome
and hearing loss and especially, frequent otitis media
is common in patients with Down syndrome as well.
They may develop eye disease such as cataracts or refractive errors.
They may develop poor growth.
In fact, patients with Down syndrome should be plotted
along their own special growth curve which is available online.
They may have increased risk for celiac disease,
they may have atlantoaxial instability.
So, atlantoaxial instability is instability of C1 on C2 of their vertebrae,
we used to recommend x-ray screening.
Though, now we?ve decided that is no longer particularly beneficial.
Although it may be required for participation in the special olympics
which is important for these kids.
Additionally, they may have an increased risk of Leukemia
and that is very important.