[Lecturer] All right.
We are
talking about congenital anomalies, basic dysmorphology
and genetic assessment.
This lecture uses slides that go along with the chapter
in the BRE genetics nursing book.
And I have added to them quite a bit
to
fill out the information
and the value of the basic overview.
So
we will proceed now.
So
I wanted to
frame the discussion about dysmorphology
in the context of clinical assessment process
and our overall aim in
clinical genetics diagnosis of
collecting a set of information
that we, basically, use pattern recognition,
or human skills in pattern recognition
to
identify a pattern that is quote, "recognizable, end quote.
So our clinical
exam
basically goes through a set of features.
We look for features,
and we list the ones that we find,
feature A, feature B, feature C,
and we
then take that
feature set
and see if we recognize a pattern
that is
typical of or almost typical of
what is seen in a particular disorder
and a pattern that is not broadly seen in other disorders
or in normal individuals.
So that's really our goal.
So we come up with, from the pattern analysis,
a differential diagnosis
of a set of disorders that this might represent.
Sometimes it's very clear there's only one,
sometimes
it's complicated,
and you might put a list of three or four disorders
or maybe more.
The feature set can also rule out disorders.
So you might start out
with a pretty long differential diagnosis list
and then cross things out because key,
or characteristic features of a disorder are not present
or there are other features
that make it pretty unlikely that disorder
should be considered any further.
So both adding and subtracting disorders
from the differential diagnosis is our intermediate goal.
And then once we have that list, we can say
is there additional testing, additional clinical information
that can help us differentiate between those
or should we just send it on to someone
who knows a little bit more about these kinds of things
and what the most efficient
next steps are?
So I listed feature A, feature B and feature C
as clinical things we find, for example, on exam,
but the pattern is really
a multi-axial
data set.
So you have the physical exam features
but there's also things about the history,
when did the obesity start,
what were the early speech development history,
those kinds of things,
as well as family history,
behavior.
This is something that is often overlooked, is specific,
I would say characteristic behaviors are
observed in a number of disorders,
and the presence or absence of those behaviors
or personality traits
or speech characteristics can sometimes really help you
narrow down that differential from the pattern.
We'll talk a little bit about measurements.
I'm trying to move from a subjective feature
declaration to something that is objective.
And
also
the
value of testing and lab results,
usual types of non-genetic testing
will also potentially fit into the pattern.
And finally, tests
or assessments such as
IQ or a developmental assessment
and the outcomes of that will also be very important
in trying to
create a full, rich pattern set
to
help us differentiate what disorders we're really looking in
or what are the next scanning types of genetic testing,
which we'll talk about in a later module,
that are going to be most productive
in trying to understand what's going on.
So
we have, essentially, defined a process here,
but it's worth recognizing that the process is, essentially,
going from effect backwards toward cause.
So we're trying to understand what the underlying cause is
in terms of the genetics, the proteins, the functions,
and how that
relates to effect 'cause we're not there
when the embryo is developing
or when the brain is developing and during the fetal growth.
What we can see is the downstream effects of that,
and so we are trying to capture those downstream effects
and then work, in our brain, backwards toward
a sense of what are the kinds of things that went wrong
or went different during embryonic or fetal development.
All right.
So dysmorphology is a
area of genetics in which there are,
of specialization, essentially.
And it comes from, I think it's probably Greek,
dys for painful and morph for shape,
so painful shape, not really so much.
I think it's really things that are different,
and noticeably different.
And it's really the study of congenital anomalies
or abnormal patterns of development.
Not all of them are genetic.
All right.
So first step is identification of anomalies
can lead to an accurate diagnosis.
So why do we study dysmorphology?
Accurate diagnosis can guide clinical management.
And we can consider
with that information within the context of the family,
as I showed on the first slide,
and we try to develop that pattern.
So here's an example of a feature pattern
for a syndrome called Noonan syndrome.
And I'm going to read through these.
Triangular-shaped face, widely spaced eyes,
downward-slanting palpebral fissures,
drooping eyelids,
or ptosis, P-T-O-S-I-S, ptosis,
low set ears, high or prominent nasal bridge,
short webbed neck.
Those are actually two different things.
A short neck is a short neck
and a webbed neck is a webbed neck,
sometimes they occur together.
And congenital heart defects,
in particular Noonan syndrome,
you look for pulmonic stenosis,
the stenosis of the pulmonic valve.
And occasionally we'll pick up a kid with Noonan syndrome
because the cardiologist identifies
pulmonic stenosis, even a mild pulmonic stenosis.
And the clinical features are not so obvious,
but when we take a look, there's enough suspicion,
and we do genetic testing and identify
that this patient really does have Noonan syndrome.
Okay.
So
what are these features?
So we put them in words
when we put them in our notes in the chart,
and we put them in words
when we write a paper about a disorder,
and we put them in words
when we're searching through databases
to
try to find a match for a feature or pattern
that we're not
recognizing upfront.
I do a lot of that.
So one of the challenges is in converting
what you see on exam or what you feel on exam
to one of these terms,
one of these verbal, word-based terms.
So I'm gonna show you some pictures
that go along with these features.
First one is triangular face.
So you can see from these pictures,
these two boys
have a triangular face,
and it's much wider at the top
and much narrower at the bottom of the face.
Wide-spaced eyes,
or
the old-fashioned technical term is hypertelorism,
meaning that the center of the eyeballs, not the edges,
but the center of the eyeballs,
we measure that from the pupils,
measures wider than usual.
This patient also has two other dysmorphic features
that I'll let you try to figure out from these pictures.
The third one is downward-slanting palpebral fissures.
The palpebral fissures being
the opening between the upper and lower eyelids.
And this patient has,
basically, if you draw a line from the inner canthus,
try and get you an arrow here,
the inner canthus to the outer canthus, it's not horizontal,
it goes down
on both sides typically.
This patient also has proptosis, prominence of the eyes,
eyes that stick out almost to or beyond the eyebrow arch
and relatively-large looking eyes.
All right.
The next feature is drooping eyelids,
or ptosis, P-T-O-S-I-S.
Here's a girl with unilateral ptosis.
She has an eyelid that droops down over the other one.
It's more obvious when it's unilateral,
but in Noonan syndrome, it's usually bilateral.
And one of the things
that individuals with significant ptosis do
is that they tilt their heads back
because they need to look under their low-lying eyelids
in order to see well.
So sometimes they don't know that they're doing this,
and you can lift their eyelids up and say,
"Is that better?"
And if it is better,
then they may need to go see an ophthalmologist
to see if they need some surgical management
of their ptosis.
Low set ears,
basically the ears fall.
This is a line drawn between the inner canthi of the eyes.
And
if the outer helix,
or the root of the helix fall significantly below that line,
then that's low set ears.
Ears can also be rotated, in the case of Noonans
are often rotated posteriorly.
I'm gonna point you back over to this kiddo here.
If you draw a line between his inner canthi here,
then you will see that that line,
his whole ear is below that.
So he has low set ears as well.
A high,
or prominent nasal bridge
means this part of the nose between the eyes,
part of the nose between the eyes, that's the bridge.
And it is high when
it
sticks out further than average.
And in a couple of these, forms of a continuous line
without a dip between the forehead and the tip of the nose.
The webbed neck.
Here's a couple pictures of webbed neck.
These are usually the result of
backed up lymphatics around the neck,
posterior neck in particular
in
the early or mid embryonic life.
And these are the residua of those.
So these are both webbed necks.
And sometimes they're more apparent from behind.
Okay.
So the other one I missed there
was congenital heart defects, Noonan syndrome,
and we already talked about that.
All right.
Major anomalies.
So we divide the anomalies
between those that are major and minor.
Major anomalies are serious,
things like cognitive impairment,
which really is a malformation of the brain.
It's often due, not necessarily to things
that are visually structurally different
on an MRI or a CT scan,
but a difference in the organization
of the neural layers in the brain as it develops,
and that affects the efficiency
of information management in the brain.
Heart defects, renal agenesis.
So those are examples of major anomalies
that often require medical or surgical attention
and can have life-threatening implications
or serious cosmetic effects.
Okay.
Minor anomalies typically have no serious functional
or cosmetic consequences,
and so they're treated mostly as clues
toward an underlying disease process.
Minor anomalies also
can be seen in
a unaffected population,
but they're usually not very common.
Somebody made up a number and said
it's found in fewer than 4% of the population.
Not sure that that's
necessarily a number to hang your hat on,
but the idea is minor anomalies are called anomalies
because they're not present in most everybody.
But they can be present in people
without a genetic dysmorphic condition.
Most dysmorphic features are classified as minor,
and several minor anomalies appearing together
can be enough if that pattern
is rare enough and unique enough
to lead you toward a correct diagnosis.
All right.
Here's an example of a minor anomaly called clinodactyly.
Dactyly of course referring to fingers
and clino referring to a curve,
so it's a
curved digit.
It's usually curved inward,
as in this fifth digit here.
It's often the fifth finger that's curved inward
toward the other fingers.
This fifth finger clinodactyly feature
is found in 10% of the normal population,
but it's a
almost invariant feature of Down syndrome.
I have seen a couple of Down syndrome kids
in whom this feature was not really very prominent,
so it doesn't necessarily rule it out,
but you gotta question your diagnosis
when you're not finding that.
Okay.
So we're talking about
terminology again.
So a malformation is a primary problem
with growth or development.
In other words, the growth or development program
said, "Make it this way instead of the usual way."
All right?
An example is cleft lip,
which is failure of the lip and or the palate tissues
to fuse together during development.
So there's something about the program that said,
"You know, you've gone far enough,
you don't have to really close this upper lip."
And there wasn't anything that got in the way
or anything that was toxic.
That's a malformation.
A deformation, in contrast,
is
a physical change
that's due to a physical or mechanical force
that is preventing the proper growth and development
of a structure that would have otherwise developed.
Examples are not enough space in the womb,
so oligohydramnios,
so not enough amniotic fluid.
The baby's ear may be
folded over
and pressed against the inside of the womb
for weeks at a time,
and that may change its growth or position
or how it looks when the baby comes out.
Multiples means twins, triplets, quadruplets, whatever
they tend to have,
and can have
deformation,
areas of the body that were deformed
by their local environment in the womb.
A disruption is different again.
It is a normal developmental process
that is disrupted by an event
that leads to the destruction of normal tissue.
A drug exposure, a teratogenic drug exposure,
prenatal trauma, vascular insufficiency.
This may be something that's very unpredictable
and there are examples of a number of features
that are believed to result from
a clotting of a particular
anatomical field,
a clotting of the arterial supply
such that that arterial field
stops growing or actually can involute
because it has lost its blood supply.
Some infections that target certain areas
may also cause physical disruption.
All right.
This is an example of a disruption anomaly.
So here's a child with
a third digit, where the end of the digit is shriveled up,
and it's got
a belt line here,
where somebody's cinched up a belt, it looks like,
so this is probably a vascular
event, where the tip of this finger
lost its vascular supply.
Those are not usually genetic,
and so don't necessarily indicate a genetic syndrome.
Okay.
Another form of malformation is dysplasia,
which means the alteration
in the size, shape and organization of cells.
And the most common cause of that is single disorders.
And an excellent example is ectodermal dysplasia.
So let's parse that down to
dermal,
so it has to do with the skin.
The ectoderm is the outer layer of the embryo
that leads to skin and a number of other
elements including the GI tract,
the inner linings of the GI tract.
And ectodermal dysplasias also
can affect ectodermal appendages such as nails,
hair, lashes,
mammary glands.
Teeth are part of the ectoderm,
so ectodermal dysplasias may affect
the maturation of a number of features
in
the ectoderm,
and that's a dysplastic pattern.
So what's a syndrome?
So a syndrome is a collection of features
that occur together and have a consistent pattern.
They're thought to have the same cause.
And an example is Down syndrome,
which we've touched on
a number of times in this course already.
So think of a syndrome
as this collection of features that occur together,
have a consistent pattern that is not commonly seen
outside of individuals with the syndrome.
All right.
What's the difference between a syndrome and a sequence?
So a syndrome, I'm gonna go back.
A syndrome is thought to have,
all of the features are thought to arise
from the same underlying cause.
Okay?
A sequence is where some of the features
are actually secondary
to a primary single anatomical cause.
So one anomaly starts a chain reaction
that causes another problem, which then causes another
and then sometimes another.
And the typical example of that is Pierre-Robin sequence,
not syndrome but sequence.
It begins with
a micrognathia, a small jaw, a very small jaw,
which is a growth defect in the mandible
in the developing fetus.
And what it results in is less room for the tongue.
The tongue is hanging out there
and
is not allowing
the two shelves of the pallet to flow together
because tongue is occupying space
that is higher than normal
because its normal lower position is not there.
I mean, the room is too small.
You booked too small of a birth on the train.
And the tongue may also be forced backwards,
which can lead to respiratory obstruction as well.
So kids with it, that are born with severely
small jaws often have two things going on.
They have a cleft palate
because the palate wasn't allowed to close,
and
they have a high risk of respiratory obstruction
at the base of the tongue.
All right.
What's an association?
So these are all terms that we
use to
explain
the difference between things that are
genetically programmed,
and things that we observe together
for different reasons.
So an association is a collection of features
that occurs together
but the causal relationship is not clear.
And sometimes when we learn more,
the name may change to a syndrome or sequence,
but sometimes it doesn't.
So for example, the VACTERL,
or V-A-T-E-R is a shorter version of that,
association is one
which has overlap with genetic syndromes
that are caused by single genetic changes,
but we
often see
patients who rule out for those other syndromes
who still have this pattern of features.
It's not a syndrome but an association
because we see them together
but they don't clearly have a common cause.
VACTERL is an acronym that stands for vertebral anomalies,
anal stenosis or
atresia,
cardiac anomalies,
tracheaesophageal fistula,
renal anomalies, renal or collecting-system anomalies
and limb anomalies, particularly
radial rays.
So the thumb, the base of the thumb and the radius
of hands and arms.
So a gestalt is a German word that basically means
it really looks like
it has this undefinable,
undissectable feeling that's recognizable.
So it's an overall impression,
it's a whole pattern or picture,
and it often requires much clinical experience
with patients who have anomalies and their families.
So for an example that I would give personally is that
if a patient comes for developmental delay
to see me in clinic, I can open up the door,
see the 2-year-old and say,
"That patient has Williams syndrome,"
because the gestalt, to me, is very characteristic
without me going through and listing
each of the dysmorphic features that that patient may have.
All right.
If you work in a newborn nursery a lot,
you will eventually get a really good gestalt feeling
for Down syndrome.
The gestalt isn't always accurate,
which is why it's helpful to have a systematic way
to assess the individual features
and convince yourself that you're feeling from the gestalt
is actually confirmed by looking at the feature set
that's expected for that syndrome.
Fetal Alcohol Spectrum Disorder
is a
spectrum, as indicated,
that is
a teratogenic syndrome.
So that means a teratogen is a substance which is toxic
in the fetal period.
So substances such as alcohol
can alter the development and cause a birth defect
or a set of birth defects.
The birth defects that you see
may depend on
what gestational age that teratogen
was present
and what pattern of
teratogen exposure there was.
So was it a low level of alcohol exposure every day
or was it a high level?
Periodically those may change
the impact of those teratogens on the development.
Maternal and fetal genes related to alcohol metabolism
and clearance are probably implicated
in whether or not
Fetal Alcohol Spectrum Disorder comes together
but
the primary inciting factor is the alcohol teratogen.
All right.
Here's a picture of a person with features
of Fetal Alcohol Syndrome,
and on the left there's a
listing of the individual dysmorphic features.
So a small head, microcephaly,
epicanthal folds,
which we're gonna go through in more detail,
a low-nasal bridge, small eye openings,
which means the measurement
from the inner to the outer canthus,
from here to here,
is shorter than usual.
We call that short palpebral fissures.
A shorter, upturned nose,
a flatter midface,
so the zygomatic arches here tend to be less prominent.
The philtrum,
which is that
patch of
skin between the base of the septum, the nasal septum,
and the top of the upper lip is smooth.
So in most people,
if you drive from one corner of the mouth,
and you drive up a little bit,
and you drive over, you go over a little hill,
and then you're in a little valley,
and you go over another hill,
and then you're back sliding down the outer slope
to the outer edge.
So people with a smooth philtrum,
it's more like a gentle rise or a flat desert
as you take that road trip.
So the last feature is a thin upper lip,
or a thin upper vermilion border,
narrow upper vermilion border.
Vermilion is a color
which people think refers to the color of the lips.
So that vermilion border is
what's in between the skin on the outside
and the mucus membrane on the inside.
And if that is thin then you have a thin upper lip.
And then some degree of micrognathia,
or undeveloped jaw.
Here's another picture down here
of an individual with a thin vermilion border.
This person doesn't have so much of a smooth philtrum,
and you can see that going over the two humps
of the mountains or the camel there.
All right.
Our genetic assessment.
We looking, again, for head-to-toe pattern.
We have a standard physical assessment procedure.
I have a fairly standard exam
procedure.
We screen for the presence of major and minor anomalies.
These inform our decisions
for referral to genetics professionals
or preliminary testing.
We consider the context of the family,
consider the behavioral profile
and consider the timeline of feature and development.
Cognitive impairment.
And I touched on this in the first slide.
So a major reason for evaluation by genetics professional.
This says more than 500,
but it's probably a lot more than that,
can cause cognitive impairment.
In early childhood, we see that as developmental delay.
So
a lot of our evaluations are on
infants, toddlers and children with developmental delay.
This is considered a major anomaly.
It can be syndromic or non-syndromic,
meaning that
a non-syndromic cognitive impairment disorder
may not have facial features that are different,
may not have digital features that are different,
may not have anything on the outside
that strikes you as different
or strikes you with a gestalt,
and so that may also be
a genetic disorder.
I'll mention here also
the
conflating factor of
different
characteristic features
of different ethnic backgrounds and races.
So those are things that one needs to be
aware of and intuned to.
This is really about learning about diversity.
What does somebody from Nigeria really look like
and how is that different in a normal context than others?
And to try to subtract that from your assessment
of dysmorphic features and patterns
as you're going through your assessment.
Getting back to cognitive impairment.
Here's a list from the book, table 9-1,
of a number of syndromes
which can cause cognitive impairment,
and I won't go through them in detail.
Measurement.
So qualitative descriptions make comparisons over time
and between clinicians difficult.
So sometimes we say
let's look at the physical measurements
and compare them to
standard measurements,
that is measurements of
what is the mean, what's the standard deviation,
so these bell curves
or things that you will recognized from your training
as, like, growth charts, okay?
Similar kinds of charts for physical measurements
that help us identify body parts that are out of range,
out of expected range for their positions or sizes.
So, classically, we look at the eye.
I talked about hypertelorism early in this lecture,
wide-spaced eyes.
That's C here.
You measure the distance between the center of the pupils.
I like to use
a clear, plastic ruler, one that's flexible,
without sharp points and stuff so that children,
they can see through it a little bit,
and they're moving around or unlikely to result in a injury.
So you measure the distance between the pupils,
or interpupillary distance,
the distance between the inner canthi
or an inner, I-N-N-E-R, canthal distance.
You measure the distance between the outer canthi,
you try to estimate 'cause sometimes
the eyelashes get in the way,
so you try to estimate where
those two skin pieces come together
to form the outer canthus.
And then measuring the philtrum,
which is from the base of the nose to the
edge of the upper vermilion border.
Okay?
And then I put over here the ear length as well.
The ears are measured
on their longest axis, which goes from the tip of the lobe
to the upper edge of the helix.
And there are tables with
standard curves against the same, like, growth curves,
you know, against age
that are in some of the classic genetic books.
And you can find them online as well.
Variations in height and weight,
the patient's height and weight
in the range normal for thier age
inconsistent with those of family members.
So we look at mid-parental age,
excuse me, mid-parental height
and look at the percentile for that,
and say, "Is he running above or below expected height?"
And we look at that on normal growth curves.
Some disorders will have their own growth curves.
You can look at the height and weight
on those growth curves.
Prader-Willi Syndrome
is an example of a syndrome with variant growth.
It includes increased body weight due to hyperphasia.
They, basically, don't
have a sensation of satiety,
or being satisfied after eating.
And that characteristic starts around
two to four years of age.
If you see increased body weight occurring well before that,
probably not Prader-Willi Syndrome
because, in fact, in infancy
Prader-Willi Syndrome has a low body weight,
they have a lot of feeding difficulties.
They're scrawny, little kids,
and they have generalized hypotonia,
or low muscle tone.
So another pattern that you can recognize in early infancy.
So chronic feeding difficulties and significant hypotonia,
you might ask the question,
"Does this child have Prader-Willi Syndrome?"
All right.
Genetic diseases with stature variations.
Two
extremes.
One is achondroplasia, which has very short stature.
You've noticed people on television, actors
and families with achondroplasia, mid-face hypoplasia,
frontal bossing, short limbs.
Marfan syndrome
actually causes the long bones to grow longer.
So they have tall stature, long limbs,
and it's considered a connective tissue disorder
with additional
clinical risks.
So both of these are things
you can Google images on the internet and
find examples of that.
Dysmorphic features of the skull
fits into the general category of craniofacial anomalies.
Plagiocephaly is a significant asymmetry of the skull.
These first four pictures here on the right,
if you're looking from the top,
it often helps to look from the top to see what's going on.
And there is not a nice symmetric oval.
So there's an asymmetry here.
It can be due to positional effects
or it can be due to premature
closure of some of the sutures
in
the skull.
Craniosynostosis is premature closure of those sutures,
and it happens early enough
you may get a rather dramatic shift
in the direction of growth of the skull
because the brain is still growing underneath it,
and the skull needs to grow,
but if it's unable to grow in one direction
because that suture has already fused,
then you
get this.
If you fuse a bunch of sutures,
then you can restrict brain growth,
get increased intracranial pressure,
and that's a bad thing.
You need to pick that up early.
Scalp defects, aplasia cutis congenital,
which basically means you were born with a spot on your skin
that either didn't form or formed very poorly.
It's often on the scalp,
but you can have more complex forms of this.
And it's usually a single scalp lesion
that looks like a punched out region
with a very, very thin, almost translucent
or scar-like
tissue in it because it, basically, didn't form
normal skin there.
It can be very small to very large.
Sometimes you have to dig through the scalp to find it.
I don't mean dig, I mean just, you know,
part the hair to look for it.
It may heal before birth
but it's still going to have this parchment-like skin
or scar or absent skin.
And there's typically no hair
in this little circumscribed, punched out area.
And you can Google that online as well.
So I can't put pictures up for everything
because I can't guarantee that they're royalty-free
if I just find them on the internet.
But you can go look on the internet and find them.
Okay.
Macrocephaly is an enlarged head,
and it
is
a head circumference,
or occipital frontal circumference
greater than 97th percentile for the same age and gender.
So there are charts for boys and girls,
same as height and weight.
And we measure from the frontal region,
just above the eyebrow ridge
to an area near the top of the occipital bone.
And really, you know, when I measure
because different patients have different head shapes,
I, basically, am measuring
the largest front-to-back circumference of the head.
So I put the measuring tape around the head
and I scoot it up and down
until it pulls out to the level that is the maximum.
And that's what I use for my measurement.
Microcephaly is the opposite, small head,
head circumference that's more than two standard deviations
below what's expected for age and gender.
This is a picture from the book-generated slides.
It doesn't have text with it,
so I'm not sure why it's here,
but there are dysmorphic features here.
I will point out while you're looking at it,
that
there's a wider gap between the first and second toes.
We call that a sandal gap.
And then there's something different
about the second and third toes on both sides,
which is that they're lacking the space between them
at the proximal ends,
and we call this partial cutaneous syndactyly
'cause it doesn't look like the bones are actually joined,
it's just the skin.
And there's another term
that this goes by, which is zygodactyly,
or brothers,
think digits that are brothers.
And when they're in this two-three position,
a little bit of zygodactyly can be a familial trait.
More of it in the context of, say,
a long philtrum, short upturned nose,
cleft palate would really point you
toward a disorder of cholesterol metabolism
called Smith-Lemli-Opitz syndrome.
Coarse features is something else
that's a subjective thing that we often talk about.
The book uses this picture on the left for coarse features.
There's somewhat fuller lips,
a sense that the mouth isn't closing all the way,
maybe a larger tongue.
This person also has up-slanting palpebral fissures,
and
a little bit of a prominent
eyebrows.
These kids have other disorders
which are really characterized
by the coarseness of their features.
So
thick lips,
exaggerated creases, thick, bushy eyebrows
and prominent brows.
Here there's some little differences in the ears as well.
So coarse is one of those gestalt feelings
that
you need to work with for a while
before completely understanding.
When we think about coarse,
it's one of those trigger words to think about
lysosomal storage diseases.
So
philtrum is, again, that space
between the bottom of the lip,
I mean, I'm sorry,
the top of the lip and the bottom of the nose.
Its length can vary.
Smooth philtrum is seen in Fetal Alcohol Spectrum Disorder.
It's important that the smoothness is assessed
when the person is not smiling
because smiling flattens out your philtrum.
So in the top picture here on the left,
this child really has a smooth philtrum,
has a long philtrum.
This person in the middle is not smiling,
and you can see they have their little camel's-hump
trajectory there.
But that same person, when they smile,
it looks quite smooth.
So you need to look at them in the un-smiling position.
Doesn't necessarily mean there's a genetic disorder,
again, it's one feature
that is not important in and of itself,
and we're looking for a pattern.
And that's actually helpful,
when you're looking at these features
and commenting on them,
to talk to the patient and the parent
so that they don't feel like
that every little thing that you're identifying is bad.
Okay.
We went over the Fetal Alcohol Syndrome features before.
There's
a diagnostic criteria set for Fetal Alcohol Syndrome,
for fetal alcohol effects
and for Fetal Alcohol Spectrum Disorder,
which are all
from the most physically affected
to the least physically affected with residual brain effects
that may not be evident on the exterior.
Okay, what about the spacing of the eyes?
So on the left here we see somebody
with extreme hypotelorism.
So small distance between the center of the eyeballs.
And in the middle, there's normal spacing.
And on the right side, there's a wide spacing.
Now I've added a little white patch to this person's hair
because,
again, there's a gestalt here.
If you see wide-spaced eyes and a white patch
or maybe a partially blue iris
or one iris blue and the other one brown,
that's a gestalt for a disorder
called Waardenburg syndrome.
Okay?
Palpebral fissures, we've talked about this a little bit.
So here's an up-slanting.
If you draw a line between the inner and out or canthus,
it slants up.
Here's a normal-slanting,
so more or less horizontal.
And then there's down-slanting,
going from upper to lower from inward to outward.
Prominent epicanthal folds.
And the epicanthus is a fold of skin
that overlies the inner canthus.
That's what epicanthus means.
It's a vertical fold of tissue
that lies between the eye and the nose.
And it may be a normal variation in people of Asian descent.
So, again, on your normal patients, keep an eye on this,
and try to learn what's normal
in different ethnic backgrounds
because that will help you recognize what is not normal
in both those ethnic backgrounds and others.
It's seen in a number of genetic disorders,
but it's really not quite the same.
That's why you need to look at them a lot,
and it may obscure the inner canthus.
So I've put a little thing on here to say,
you know, here's a fold that you might see
in Down syndrome, for example,
an epicanthal fold
that obscures that inner corner of the eye.
Okay?
Measuring to see if the ears are low set.
I mentioned that earlier,
and so I won't spend a lot of time on that.
Cleft lip with or without cleft palate
is a complex process and growth inhibited,
a gap may result
either through programmatic or obstruction
deformation-kinds of terms.
And it can be caused by genetics
or environmental factors during pregnancy.
Lip pits are symmetrical depressions
usually in the part of the lower lip called the vermilion,
again, that red part of the lip
between the skin and the mucus membrane.
And here, down here, are one, two, they're quite symmetric.
And those are
a feature that's almost diagnostic of a disorder
called Van der Woude syndrome.
That's autosomal dominant, has very high penetrance
but has variable expressivity.
All right.
Dysmorphia features of the hands and feet.
Polydactyly is an extra digit.
Sometimes a small extra digit might have been cut off or
put in a tight ligature at birth and fallen off.
So sometimes, if you look closely,
there will be a little scar on the outer edge of
the hand that will indicate that a digit was present there
that the patient may not actually know was removed
in the newborn period.
So we divide
the polydactyly into
pre-axial
and post-axial polydactyly.
So what's pre and post?
So we look at this sailor over here,
he's standing at attention,
and his hands are at his sides,
and his thumb is pointing forward,
and his little finger is pointing backward.
So there's an axis.
So, you know, the middle plane of his body
between front and back, that's the axial,
that's the axis that we're talking about in axial.
So post-axial is behind that axis
and pre-axial is in front of that axis.
So if the extra digit is on the thumb side, it's pre-axial.
If the extra digit is on the pinky side, it's post-axial.
So in these pictures
the first panel on the left is pre-axial.
You've got two big toes on a single foot.
You've got a little bit of cutaneous syndactyly
or zygodactyly here.
And the same thing here.
You've got
more toes seemed to be added
on that inner surface of the foot.
Here's post-axial polydactyly in the hand,
where you have a normal looking thumb,
normal first, second, third, fourth fingers,
and there's an extra one here on the outside,
okay?
So that's post-axial polydactyly.
Why do we care?
Because different syndromes have different patterns,
predominantly pre-axial, predominantly post-axial,
sometimes both,
or pre-axial on the upper extremity
and post-axial on the lower extremity, for example.
So
it's a differentiating feature
that really does help us.
Other dysmorphic features of hands and feet.
Arachnodactyly, long, slender fingers.
Arachno means spider,
so this literally means spider fingers.
And there are some tricks or direct measurements you can do
to see whether you're gestalt
sense of that is true or not.
Brachydactyly, very short fingers,
sometimes extremely short as in this case,
or toes.
And then syndactyly is fused digits.
In this case
digits 2, 3, 4, 5,
so two through five are completely syndactylic,
fused together.
And
it looks like there's a bit of polydactyly here as well
on this one,
and a broad thumb.
So put that into your syndrome search,
and see what you come up with.
Fused digits.
Also you can have partial fusion.
So here's a patient who has webbing between the fingers,
and that can be considered partial cutaneous syndactyly.
This looks like the hand
of an individual with Aarskog Syndrome.
So that's something you can look up.
Dysmorphology of the joints,
greater or lower range of motion.
Hyper-mobility or hyper-extensibility
are the terms that we typically use.
We think of Ehlers-Danlos syndrome,
which is really
a large group of connective tissue disorders.
Some of them have fragile blood vessels.
We need to differentiate those from the ones that don't,
that just have hyper-mobility or hyper-extensibility
and soft, velvety and elastic skin,
hyper-mobility.
And then
it's important to recognize
that there are diagnostic criteria
for Ehlers-Danlos syndromes,
the different forms of Ehlers-Danlos syndromes,
and that not everybody with
the ability to pop a shoulder in and out
has Ehlers-Danlos syndrome.
We see a lot of individuals that we need to say,
"Yes, you may have some loose joints,
but you don't have Ehlers-Danlos syndrome."
And there's no genetic testing
for the hyper-mobility type anyway,
so we can't do any testing to, you know,
change what's going on here.
In 2017,
there was a international meeting
that culminated several years of experts working together
to tweak the international classification
of Ehlers-Danlos syndrome
and to create the diagnostic criteria for those.
So that's really what we work from these days.
And that's a really good resource to go by.
There's a whole issue of a journal that was addressed,
two articles that address Ehlers-Danlos syndrome
and its various types.
So we're nearing the end of the lecture,
and I just wanted to throw out another recommendation,
which is a book called "The Bedside Dysmorphologist".
It's a small book, you can have it on, you know, online
for about somewhere around $60.
It's in the second edition.
I bought the first edition actually,
and had it signed by Willie Reardon,
who is an old friend of mine.
And I haven't even actually looked at the second edition,
but I suspect it's even better than the first.
So what's nice about this book
is that it takes you through the process
of recognizing one dysmorphic feature
and then saying what other dysmorphic features
might go along with it,
and look for those,
and that helps you decide
what are the next steps to do.
It's very concise. Has great pictures.
Not a big book.
So if you're interested in this or
have a sense
that this is gonna come up frequently in your practice,
this is probably one of the go-to books.
The other book that you're maybe familiar with
is Smith's "Recognizable Patterns of Human Malformation",
which is in its seventh edition.
This is our geneticist bible
for
the more common
dysmorphic syndrome feature descriptions and pictures
somebody in your office has,
that's probably sufficient.
You don't necessarily need to buy it.
I think it's about 80 or 90 bucks now,
and it's a bigger, thicker, more detailed book.
So if you're an aficionado, this might be fun,
but if you can get access to it in your library
or somebody in your practice has it, then I wouldn't buy it.
All right, so that's the end.