00:01
Hi. Let’s now review
Turner Syndrome.
00:04
It’s really important that you
pay attention to this lecture
as you will find there are
a lot of exam questions
regarding this
very rare syndrome.
00:12
How rare is it?
Well, the incidence of Turner Syndrome
occurs in 1 in 2,000 females worldwide.
00:20
Let’s now review the
genetics of Turner Syndrome.
00:24
The X chromosome as you know,
contains nearly 1,000 genes
which relates to 5% of the
total DNA in the cells.
00:32
That’s a lot.
00:34
So let’s review what
we find normally.
00:37
In 46,XX individuals, one of the X
chromosomes would be randomly inactivated.
00:44
With classic Turner Syndrome,
the karyotype is 45,XO.
00:49
When I was a student,
I remembered it as kisses and hugs.
00:52
45,XO from Tina Turner.
00:55
Maybe that will help you.
00:57
It’s one of the most common
chromosomal abnormalities.
01:00
It occurs in 0.8% of all zygotes
and is commonly found in
spontaneous abortions.
01:10
Fewer than 3% of these
zygotes will survive to term.
01:14
That means 37
weeks, making 45,XO,
a common karyotype again found
in spontaneous abortions.
01:24
Let’s review again
a little bit more.
01:27
If this is too detailed for you, you can
download the information and keep going.
01:32
The absence of the structure abnormality
of one copy of the X chromosome
is often due to nondisjunction.
01:40
This is a sporadic condition that’s
possibly related to advanced paternal age.
01:45
But there are also reports that about
70% of the missing maternal X chromosome
is why we have Turner Syndrome.
01:51
It’s actually not
related to maternal age,
but it’s possibly
related to paternal age.
01:56
Let’s again review the
cytogenetics of Turner Syndrome.
01:59
About half of patients with Turner
Syndrome have a genotype of pure monosomy,
which means they have
a 45,XO karyotype.
02:07
Another half are mosaic, which means
that some of their cells may be 45,XO
and some of their
cells maybe 46,XX.
02:14
The phenotype may be less
pronounced in girls with 46,XX,
45,XO mosaicism.
02:20
But it varies depending on the timing
and tissues affected by mosaicism.
02:25
And sometimes we find that
patients have 46 X, Del (Xp)
with the deletion of the short
arm of the 2nd X chromosome.
02:33
The short arm is
abbreviated p for petit.
02:39
With the Turner Mosaics,
you can have 46,XY, 45,XO.
02:45
This is found in a minority of
patients who have Turner Syndrome.
02:49
About 6-11%.
02:51
I doubt this would
be on your exam
but it’s important to know
that these Turner Mosaics
that have a Y chromosome,
can actually be a ambiguous
genetalia presentation.
03:04
If you’d like to know more about
congenital adrenal hyperplasia
and ambiguous genetalia,
please download
that lecture series.
03:11
Now, let’s go back to the cytogenetics of
Turner Mosaics who have a Y chromosome.
03:16
They again can have a
variable presentation
with increased clitoromegally,
which is a longer than normal clitoris
or they can have
ambiguous genetalia
or they can have undescended
testes or descended testes.
03:32
There is a critical
need to assess
for gonadoblastoma if a
Y chromosome is present
because 12% of these
patients can have this
tumor even at a very young age.
03:45
Lets now review the
ABC’s of Turner Syndrome
that is classically
45,XO or monosomy.
03:53
The ABC’s was actually
created by a mentor of mine.
03:57
A stands for audiology.
03:59
These patients have hearing problems
and can become deaf long term.
04:04
A stands also for autoimmunity.
04:07
So they have increased rates
of rheumatoid arthritis,
lupus,
and other autoimmune diseases
that can affect
their overall health.
04:15
C stands for cardiac defects.
04:18
So these patients definitely need to
be followed lifelong by a cardiologist.
04:23
D stands for dermatologic
manifestations.
04:27
They can have pigmented nevi as you can
see here, displayed in this cartoon.
04:32
They can also have
failure to grow.
04:34
So they tend to
have short stature.
04:37
The X chromosome has a series
of genes called the SHOX genes
and they are related to stature
and bone and tendon formation
which results in the
deletion of the SHOX gene
actually causes the short
stature and failure to grow.
04:53
And lastly, they can have
gastrointestinal diseases
that need to also be managed.
04:59
Okay!
With the Turner syndrome patients
clearly they can have abnormal genetics,
they can have metabolic disorders,
they can orthopedic complications,
they can have psychosocial
manifestations of their disease
as well as renal anomalies.
05:15
So pay attention, because this
could be tested on your exam.
05:19
30 to 50% of those with Turner
Syndrome will have a horseshoe kidney
as the most common
renal abnormality.
05:26
They can also have a reproductive
and pubertal disorders
and we do talk about this in another
lecture called primary amenorrhea.
05:35
They can also have
X-linked disorders.
05:38
Clearly this occurs because
they only have one X chromosome.
05:42
When the normal phenotypic and
genetic female has a 46,XX,
so she has 2 X chromosomes making her
less susceptible to X-linked disorders.
05:54
The presentation of Turner
Syndrome upon delivery
is sometimes vary depending on whether
they are pure monosomy or mosaic.
06:04
But sometime you can see that
20% to 30% of the diagnoses
are made in the neonatal period.
06:10
The mosaics tend to be
diagnosed later in life.
06:13
Usually they fall off
their growth chart
and they’re discovered
by their pediatrician.
06:18
35% again will present
a short stature,
likely because they've fallen
off their growth charts.
06:25
That’s why the growth charts
are important to follow.
06:29
30% will present as adolescents
or young adult women
who again have
primary amenorrhea
which means they’ve never had a
period or they have a delayed puberty.
06:39
You can see here
in this graphic,
this young woman is short.
06:43
She has the stigmata.
06:44
She has the webbed neck,
she has the broader chest,
she has no breast development and you
can see also the she has no pubic hair
which you typically do see some pubic
hair with the Turner Syndrome patient.
06:58
Now, again,
let’s talk about some of the details
that you see in a
Turner Syndrome patient.
07:03
Prenatally, neonatally,
and in adolescence.
07:07
This maybe a little too
detailed for your test.
07:10
If you’d like to skip on
ahead, you’re free to do so.
07:13
But let’s review now
some of the details
of a prenatal diagnosis
of Turner Syndrome.
07:18
There are some ultrasound
finding that we see
and fetuses who present
with Turner Syndrome.
07:24
Typically, during pregnancy you
have a growth skin or anatomy skin.
07:30
These patients will be small
and that is called intrauterine
growth restriction or IUGR.
07:36
They will have a large
septate cystic hygroma,
which usually sits on
the back of the neck.
07:41
During ultrasound
you can see this.
07:43
And this is pathognomonic
usually for Turner Syndrome.
07:47
They can just have
some nuchal thickening
which is seen upon ultrasound.
07:51
They can have a short femur,
which actually correlates
to short stature
and they tend to
have total body,
lymphangiectasia
and cardiac defects.
08:02
In the neonatal period,
we can have some other physical findings.
08:06
So remember, in the prenatal period
they have IUGR or growth restriction.
08:11
This leads to low birth weight.
08:13
They can also have some lymphedema
of the lower and upper extremities.
08:17
This occurs in 30%.
08:20
They can have a webbed neck but
sometimes that’s hard to see.
08:23
They can have a high arched palate
so you need to open the mouth
and examine the
palate upon delivery.
08:30
They can have low set
but prominent ears
and they may have a low posterior
hairline and micrognathia.
08:38
In adolescence, the most common
presentation is short stature,
followed by amenorrhea.
08:46
They can also lack secondary
sexual characteristics
and in this case that would
be breast development.
08:52
30% of Turner patient undergo some type
of spontaneous puberty, but may rest.
08:58
They may have not achieved
a Tanner 5 stage breast
and not achieve Tanner
stage 5 escutcheon.
09:06
Let’s discuss in another lecture where
we review thelarche and pubarche.
09:11
Let’s now review diagnosis of
the Turner Syndrome patient.
09:15
So if all the blood
test come back normal
and it's 46,XX, but she still
have a strong clinical suspicion,
you should do a tissue
biopsy or tissue sample
to actually look
for the karyotype.
09:28
We should also always
look for the Y chromosome
with the use of FISH or PCR
for the patient who has
genitalia ambiguity.
09:38
There is no clinical warranty
for routine testing for SRY
or Y chromosomes and those
who have 45,XO pure monosomy,
without masculinization.
09:52
Let’s review short stature
in Turner Syndrome.
09:54
So again, this is our
patient who is short-statured
and has all of the appropriate
stigmata for Turner Syndrome.
10:01
She is short, she has the webbed
neck, she has the broader chest,
no sexual secondary
characteristics that we can see.
10:08
They are shorter on average,
20 cm shorter, than their peers.
10:13
This cause a lot of
distress in the patients
and remember to be sensitive to
that as you see these patients.
10:19
Remember, that they usually are born
after having a diagnosis of IUGR
or growth restriction
that’s intrauterine.
10:26
They usually have a
slowed childhood growth.
10:29
So as their peers are having
their acceleration of growth
which is the first sign of puberty,
these girls are not growing.
10:36
They may have mild skeletal
dysplasia, upper to lower ratios,
and so,
they again appear shorter.
10:45
Again, remember, and this is a high
yield fact which could be on your exam,
they lack the
pubertal growth spurt
that you typically would
see during the puberty.