Basic-concepts-dysmorphology-Temtamy-2013.pdf

Basic definitions used in approach to dysmorphic child

1. BasicConceptsin Basic

Concepts

in

Dysmorphology
Samia Temtamy* & Mona Aglan**
*Professor of Human Genetics
**Professor of Clinical Genetics
HumanGenetics&GenomeResearchDivision Human

Genetics

&

Genome

Research

Division
National Research Centre, Cairo, Egypt

2. Otli O
u
tli
ne
y
Definition of dysmorphology
y
Definition of terms routinely used in the description of
birth defects
y
Impactofmalformations
y
Impact

of

malformations
y
The difference between major & minor anomalies
y
Approachtoadysmorphicindividual: Approach

to

a

dysmorphic

individual:
y
Suspicion & analysis
y
Systematic physical examination Cfi ti fdi i
y
C
on
fi
rma
ti
on o
f

di
agnos
is
y
Intervention
y
Summary Summary
2

3. Dfiiti fd hl D
e
fi
n
iti
on o
f

d
ysmorp
h
o
l
ogy
y
The term “dysmorphology” was first coined by Dr. DidSithUSAi
1960
D
av
id

S
m
ith
,
USA

in
1960
s.
y
It implies study of human congenital defects and abnormalitiesofbodystructurethatoriginatebefore abnormalities

of

body

structure

that

originate

before

birth.
y
The term “dysmorphic” is used to describe individuals
ff
whose physical
f
eatures are not usually
f
ound in other
individuals with the same age or ethnic background.
y
“
Dys
”
(Greek)
=
disorderedorabnormaland
y
Dys

(Greek) disordered

or

abnormal

and

“Morph”=shape
3

4. Definition of terms routinely used in th d i ti fbithd f t th
e
d
escr
i
p
ti
on o
f

bi
r
th

d
e
f
ec
t
s
y
A malformation / anomaly:
is a primary defect where
th i b i lt ti f t t ll th
ere
is a
b
as
ic a
lt
era
ti
on o
f
s
t
ruc
t
ure, usua
ll
y
occurring before 10 weeks of gestation.
y
Examples:cleftpalate,anencephaly,agenesisoflimb Examples:

cleft

palate,

anencephaly,

agenesis

of

limb

or part of a limb.
Cleft lip & palate
Absence of digits (ectrodactyly)
4

5. y
Malformation Sequence:
A pattern of multiple
defects resulting from a single primary malformation.
y
Forexample:talipesandhydrocephaluscanresult
y
For

example:

talipes

and

hydrocephalus

can

result

from a lumbar neural tube defect.
Lumbar myelomeningeocele Lumbar

myelomeningeocele
5

6. y
MalformationSyndrome:
Apatternoffeatures
y
Malformation
Syndrome:

A

pattern

of

features
,
often with an underlying cause, that arises from
several different errors in morphogenesis.
y
“Syndrome” from the Greek “running together”.
y
Causes of syndromes: y
Single gene disorders (e.g. Apert syndrome)
y
Chromosomal disorders (e.g. Downsyndrome) Chromosomal

disorders

(e.g.

Down

syndrome)
y
Microdeletion syndromes (e.g. Prader-Willi syndrome)
y
Polygenic disorders (e.g. club foot)
()(
y
Environmental causes
(
Teratogenesis
)

(
e.g. Rubella,
congenital viral infection, infant of diabetic mother)
6

7. Hands & feet of a patient with Apert syndrome
Down syndrome Down

syndrome
Prader-Willi syndrome
Club foot
Infant of diabetic mother
with caudal regression
7

8. y
Association:
Anassociationisagroupofanomalies
y
Association:
An

association

is

a

group

of

anomalies

that occur more frequently than would be expected by
chance alone but that do not have a predictable
pattern or unified etiology (e.g. VATER association).
Vertebral anomalies, absence of radius & anal atresia as a part of VATER
association
VATER (VACTERL)= V: vertebral, A: anal anomalies, C: cardiac, TE: tracheo-
8
esophageal fistula, R: radial, renal anomalies, L: limb anomalies

9. Deformation:
Distortionby a physicalforce of an
y
Deformation:
Distortion

by

a

physical

force

of

an

otherwise normal structure. This could be due to uterine
malformation, twins or oligohydramnios (e.g. contractures
oflimbs and
talipes
deformity
of

limbs

and

talipes
deformity
.
Talipes deformity
Multiple joint contractures (arthrogryposis
)
9

10. y
Disruption:
Destructionofatissuethatwas
y
Disruption:
Destruction

of

a

tissue

that

was

previously normal. Examples of disruptive agents
include amniotic bands, local tissue ischemia or
hemorrhage.
CC
ongenital ring constrictions with amniotic bands
10

11. y
Dysplasia:
Abnormal cellular organization within tissue
resulting in structural changes. For example within
cartilage or bone in skeletal dysplasias(e.g.
achondroplasia).
(1)
Trident hands
Tidthd T
r
id
en
t

h
an
d
(2)
Characteristic features
fhdli
Radiological findings in achondroplasia: Loss of caudal
widening (1), short long bones of lower limbs (2)
11
o
f
ac
h
on
d
rop
las
ia

12. Impactofmalformations Impact

of

malformations
y
About 3% of all children born will have a significant congenitalmalformation congenital

malformation
.
y
These congenital malformations are responsible for a
lar
g
e
p
ro
p
ortion of neonatal and infant deaths.
gpp
y
They also account for about 30% of all admissions to pediatric hospitals.
y
It is important to recognize both major and minor malformations as they may lead to the early detection and intervention of a
g
enetic disorder.
g
12

13. The difference between major and
minor anomalies
y
Major anomalies
are severe, impair normal body
function and require surgery for management (e.g.
cleftpalate congenitalheartdisease ) cleft

palate
,
congenital

heart

disease
……
)
.
y
They may be isolated or multiple affecting different body systems.
y
Minor anomalies
are primarily of cosmetic
significance (e.g. small ear, fifth finger
clinodactyly ) Theyoccurwithvariablefrequencies clinodactyly
…..
)
.
They

occur

with

variable

frequencies

in the normal population.
13

14. Significance of minor anomalies
15%
of all newborns
3%
have an associated
major
Occurrence of
single
minor anomaly
anomaly Less
common
11
%
have an associated
ma
jo
r
Occurrence of
two
minor anomalies
j
anomaly
Unusual
1%
90
%
have an associated
major
Presence of
3 or more
minor
anomalies
90
%
have

an

associated
major
anomaly
anomalies
80%
of which are
minor
anomalies
42% of idiopathic MR
have
3 or more
anomalies
anomalies
anomalies
Constitutes
71%
of
minor
anomalies
External minor anomalies in the
head
and neck region and the
hand
14

15. A
pp
roach to a d
y
smor
p
hicindividual
I-Suspicion & Analysis
pp
yp
A genetic etiology should be suspected if the child has: y
Congenital anomalies (e.g major anomaly or > 2 minor anomalies) anomalies)
y
Growth deficit (e.g. short stature or failure to thrive)
y
Developmental delay, mental deficit or developmental regression
y
Failure to develop secondary sexual characteristics
y
Ambiguousgenitalia
y
Ambiguous

genitalia
y
Funny looking kid (FLK)
15

16. 1.
History:
y
Pedigree: Consanguinity increases the risk for an autosomal
recessive (AR) disorder
Family pedigree suggestive of an AR disorder
16
Family

pedigree

suggestive

of

an
AR

disorder

17. Male patient with similarly affected male siblings or
maternal male relatives suggests X-linked disorder.
Family pedigree suggestive of an X-linked disorder
17

18. Vertical transmission suggests an autosomal dominant
(AD) disorder, specially male to male transmission.
Family pedigree suggestive of an AD disorder
18

19. History of miscarriages, stillbirths or early neonatal deaths
suggests the possibility of a parental balanced
chromosome rearrangement chromosome

rearrangement
.
Family pedigree with multiple stillbirths and abortions
19

20. y
Pregnancy & family history:
y
History of uterine malformations or oligohydramnios
tiblbtf i
may sugges
t
a poss
ibl
e a
b
erran
t

f
orce caus
ing
malformation.
y
Abnormal fetal position or weak fetal movements
suggest abnormal fetal tone.
y
Placental morphology may give clue to the diagnosis (e
.
g
. l
a
r
ge

p
lace
nt
a
in B
ec
kwith-Wi
ede
m
a
nn
(e g a ge pace a ec
ede a
syndrome).
y
Birth measurements, as symmetrical intrauterine growth retardation (IUGR) suggests early onset growth

retardation

(IUGR)

suggests

early

onset

whereas, asymmetrical IUGR suggests late onset.
20

21. y
Environmental hazards for the fetus:
If ti t( i b t i it )
y
I
n
f
ec
ti
ous agen
t
s
(
e.g. v
iruses,
b
ac
t
er
ia, paras
it
es…
)
y
Physical agents (e.g. radiation, heat….)
y
Drugs & chemicals M t l f t ( di b t llit h t i
y
M
a
t
erna
l
f
ac
t
ors
(
e.g.
di
a
b
e
t
es me
llit
us,
h
yper
t
ens
ion,
phenylketonuria…….)
y
History of growth & Development Pi i titi
y
P
rev
i
ous
i
nves
ti
ga
ti
ons
21

22. 2. Physical examination: General principles:
y
Determine if the feature is a major anomaly, minor anomaly
or a normal variant.
y
Com
p
are with other famil
y
members.
py
y
Anthropometric measurements should be used whenever possible to quantitatively identify abnormalities.
y
The growth of different parts of the body and face can be The

growth

of

different

parts

of

the

body

and

face

can

be

measured and the degree of abnormality is established by
calculating the difference between the finding and the
appropriate terminal value of the normal range using age,
sex and ethnic appropriate standards.
22

23. Findin
g
s that su
gg
est a
p
ossible underl
y
in
g
etiolo
gy
:
gggp yggy
General
y
Short stature (height below -3SD) or tall stature (height above +
3
SD) (SD=standard deviation)
+
3
SD)

(SD=standard

deviation)
A short father & son with
s
p
ond
y
lo-e
p
i-meta
p
h
y
seal
Short female with Turner syndrome
py
p
py
dysplasia
23

24. y
Failure to thrive (height & weight below
-
3
SD) or obesity
y
Failure

to

thrive

(height

&

weight

below

-
3
SD)

or

obesity

(weight above +3SD)
Obesity
Failure to thrive
24

25. Specific organ anomalies Unusual head shape
Dolichcephaly
Brachycephaly
Dolichcephaly
Brachycephaly
TrigonocephalyPlagiocephaly
Cloverleaf skull
Oxycephaly
Cloverleaf

skull
Oxycephaly
25
Brachycephaly (flat occiput)

26. Headcircumference Head

circumference

e.g. small head “microcephaly” (head circumference below -3SD)
or large head “macrocephaly”) (HC above +3SD) Microcephaly
Macrocephaly
(Hydrocephalus)
26

27. Bodyproportions Body

proportions
e.g. short spine, short limbs or long limbs…
(
1
)
(
2
)
(
1
)
(
2
)
Disproportionate shortening in patients with mucopolysaccharidosis (1) & an
autosomal recessive type of spondylo-epi-metaphyseal dysplasia (2)
27

28. Facialfeatures Facial

features
y
Eyebrows
e.g. Synophrys (fused eyebrows) y
Innercanthal distance
eg
Hypotelorism
(decreased inner
canthal
distance or
e
.
g
.
Hypotelorism
(decreased

inner

canthal
distance

or

hypertelorism (increased inner canthal distance)
28

29. Pl b l
fi ( l ti )
y
P
a
lpe
b
ra
l
fi
ssures
(
s
lan
ti
ng
)
Upslanting of palpebral fissures (e.g. Down syndrome) or downslanting of palpebral fissures (e.g. Noonan syndrome &
Rubinstein-Taybi sndrome)
29

30. y
Palpebralfissures (length)
Short palpebral fissures (the length of the palpebral fissure is
usuall
y
e
q
ual to the distance between the two e
y
es i.e.
yq y
innercanthal distance)
Bl h hi i
Uilt l i hthl i ( ll )
Bl
ep
h
rop
hi
mos
is
U
n
il
a
t
era
l m
icrop
hth
a
lm
ia
(
sma
ll
eye
)
Unilateral anophthalmia
(absent eye globe)
Bilateral anophthalmia
30

31. E
y
E
yes
e.g. corneal opacities, heteroc hromia or other eye abnormalities
Corneal o
p
acit
y
Heterochromia
Albinism
py
Squint
Congenital glaucoma
31

32. Cataract
Epibulbar dermoid
Cataract
Epibulbar

dermoid
32
Bilateral ptosis of eyelids

33. y
Nose Nose
Short or long nose (the nose is usually 2/3 – 3/4 the length of the
distance between the nasal bridge and the upper lip)
ShSh
ort nose
Long nose
Heminasal aplasia
33

34. E
y
E
ars
Abnormal ear position (low-set, posteriorly rotated…). When
drawing an imaginary line between the outer canthus and the
occiput, usually 1
/
3 of the ear is above this line)
Low-set, posteriorly rotated ear
Low-set ears
34

35. Abnormal shape or size of the ears
Cupped simple ears
Cauliflower ears
Preauricular pit
Microtia (small or dysplastic ears)
35
Preauricular skin tags

36. y
Mouth & lips
y
Mouth

&

lips
Abnormal lips (thin/full, tented, down turned, cleft), big or small mouth
(macrostomia or microstomia)
Thin tented lips Cleft lip
Thick patulous lips
Lip pits
MacrostomiaMicrostomia
36

37. y
Philtrum
y
Philtrum
e.g. short, long or flat
Short philtrum
L fl t hilt L
ong
fl
a
t
p
hilt
rum
37

38. y
Oral cavity, tongue, palate & mandible
Tongue (e.g. macroglossia, bifid tip…)
Palate (high arched or cleft)
Uvula
(
bifid or absent
)
()
Prognathism, micrognathia (small mandible), pointed chin
Macroglossia (large tongue) with bifid tip
Micrognathia Pointed chin
38
Bifid uvula

39. &f
Hands
&

f
eet
Brachydactyly (short fingers or toes) Arachnodactyly
(long fingers or toes)
Arachnodactyly
(long

fingers

or

toes)
39

40. Cli d t l (i d fi ll fifth fi ) Cli
no
d
ac
t
y
ly
(i
ncurve
d

fi
ngers, usua
ll
y
fifth

fi
nger
)
Syndactyly (fusion of digits)
40

41. Rd ti (b )df t R
e
d
uc
ti
on
(
a
b
sence
)

d
e
f
ec
t

Hemimelia (absent forearm & hand))
Ectrodactyly (absent toes)
41
Apodia (absent foot)
Axial hand reduction (split hands)

42. Pld tl( il t il t diit) P
o
ly
d
ac
t
y
ly
(
preax
ia
l, pos
t
ax
ia
l ex
t
ra
di
g
it
s
)
Postaxial polydactyly
(pedunculated post minimus)
Complete postaxial polydactyly
Camptodactyly (contracture of fingers)
42

43. P
o
lysy
n
dacty
ly

(p
r
ea
xi
a
l
po
lydacty
ly
wi
t
h
sy
n
dacty
ly)
oysy dactyy (p ea a poydactyy t sy dactyy)
43

44. Nails& dermatoglyphics Nails

&

dermatoglyphics
Dysplastic nails with polydactyly
44
Simian crease
Abnormal flexion creases

45. Oth li b li Oth
er
li
m
b
anoma
li
es
Rocker bottom feet with sandal gap
between 1
st
& 2
nd
toes
45
Clasped thumb (adducted & flexed)
Macrodactyly (large digits)

46. SkinSkin e.g. pigmentation, scales, pterygium, appendages….
Facial hemangioma
Hypopigmented area
o
n
t
h
e
f
o
r
e
h
ead
Facial

hemangioma
o t e o e ead
Areas of hyper &
hypopigmentation of skin
46
Generalized hypopigmentation
Café-au-lait spots

47. Skin nevus
Dry scaly skin
Hyper elasticity of skin
Cutis marmorata
Hemihypertrophy with multiple skin
47
Knee pterygium
Skin appendages
with

multiple

skin

nevi

48. HiH
a
ir
Abnormal amount of hair (alopecia, hirsutism, hypertrichosis)
Alopecia
48
Generalized hirsutism
Hypertrichosis (long eye lashes)
& synophros

49. Abnormal hair line (low hair line or receding hair line) Abnormal

hair

line

(low

hair

line

or

receding

hair

line)
Abnormal hair color (e.g. white forelock, albinism)
Receding anterior hair line
with hair hypopigmentation
Silver colored hair
49
Anterior hair whorl
Hypopigmentation of
hair as a part of vitiligo

50. Neck Neck e.g. short, webbed…
Webbed neck
Chest
Short neck
Abnormal chest shape (e.g. pectus carinatum, pectus
excavatum, short sternum)
50
Pectus carinatum
Pectus excavatum

51. Nipples e.g. widely spaced, supernumerary, inverted….
Widely spaced nipples
51
Supernumerary nipple

52. Spine Spine e.g. anencephaly, encephalocele, myelomeningeocele or stigmata
of spina bifida
Anencephaly Anencephaly
Encephalocele Encephalocele
Myelomeningeocele
52

53. Abnormal jointshape or mobility Abnormal

joint

shape

or

mobility
Hyper extensibility of wrist joint
Hyper extensibility of knee joint
(genu recurvatum)
53

54. Joint& bone deformities Joint

&

bone

deformities

Bow knees
Knock knees
54
Knee joint dislocation
Multiple bony fractures & deformities

55. Abdomen Abdomen
Abdominal wall defects (omphalocele, gastroschisis)
Hepatosplenomegaly
Nephromegaly
U bili l h i
Gt hii
U
m
bili
ca
l
h
ern
ia
G
as
t
rosc
hi
s
is
Hepatosplenomegaly
55

56. Genitalia e.g. ambiguous genitalia
Micropenis
Clitromegaly
46,XX DSD
56

57. II-Confirmation of diagnosis: Lab. tests:
Idi ti f h l i
y
I
n
di
ca
ti
ons
f
or c
h
romosome ana
lys
is:
y
Multiple congenital anomalies
y
Ambiguous genitalia
y
Developmental delay with major and/or minor anomalies
y
Developmental

delay

with

major

and/or

minor

anomalies
y
History of more than 2 miscarriages
y
Indications for metabolic screening:
y
Metabolic disorders known to cause
dysmorphism
are
lysosomal
Metabolic

disorders

known

to

cause

dysmorphism
are

lysosomal
disorders, peroxisomal disorders and disorders of cholesterol synthesis
y
Radiological examination for bony changes and
neuroimaging of brain structures.
Clinical course
Similarly affected family members
57

58. III- Intervention: Treatment:
St
y
S
ymp
t
oms
y
Underlying cause
Counselling:
y
Diagnosis, natural history, prognosis, management
y
Recurrence risk
y
Reproductive Reproductive

Follow-up:
y
Identification and counselling of at risk family members S ill f li ti
y
S
urve
ill
ance
f
or comp
li
ca
ti
ons
y
Correction of diagnosis
58

59. Summary y
A congenital anomaly or birth defect is an abnormality of structure or function that ispresent at birth
Summary
structure

or

function

that

is

present

at

birth
.
y
Birth defects may be mild or serious.
y
The
p
rinci
p
les in d
y
smor
p
holo
gy
include the
pp
ypgy
determination of the underlying pathogenic mechanism
and if it is a single system or multi-system defect.
y
Accurateidentificationof a syndrome is a necessary
y
Accurate

identification

of

a

syndrome

is

a

necessary

prerequisite to providing a prognosis and plan of
management for the affected infant as well as genetic
counselingfor the parents counseling

for

the

parents
.
59

60. Summary(Cont) y
The first step towards an accurate diagnosis of a syndrome isby extensivephenotypic analysis
Summary

(Cont
.
)
syndrome

is

by

extensive

phenotypic

analysis
.
y
The severity and number of anomalies in a given
syndrome vary from patient to patient.
y
The number of malformation syndromes described is increasing everyday.
y
Itis better to refer to a clinicalgeneticistwho is more
y
It

is

better

to

refer

to

a

clinical

geneticist

who

is

more

familiar with these conditions, has access to specific
laboratory studies, dysmorphology databases and is able
tointerpret the results and provide genetic
counselling
to

interpret

the

results

and

provide

genetic

counselling
.
60

61. UflR y
Aase JM. Diagnostic Dysmorphology. Springer, 1990 Jones KL Smith
’s Recognizable Patterns of Human Malformations:
U
se
f
u
l

R
esources
y
Jones

KL
.
Smiths

Recognizable

Patterns

of

Human

Malformations:

Expert Consult Online and Print. 6
th
ed. Saunders, 2005
y
Gorlin RJ, Cohen MMJr, Hennekam RCM. Syndromes of the Head
and Neck (Oxford Monographs on Medical Genetics)
4
th
ed Oxford
and

Neck

(Oxford

Monographs

on

Medical

Genetics)

4
ed
.
Oxford

University Press Inc. 2001
y
Hall JG, Froster-Iskenius UG, Allanson JE. Handbook of Normal
Measurements. Oxford: Oxford University Press, 1989
y
Taybi H, Lachman RS. Radiology of syndomes. Metabolic Disorders and Skeletal Dysplasias. 5
th
ed. Mosby, 2006
y
Temtamy SA, McKusick VA. (1978) The Genetics of Hand Malformations. NewYork, Alan R Liss, Inc. 1978
y
Goh DLM. Approach to a dysmorphic Individual. Bulletin 17, MITA (P) No: 251/06/2000
61

62. UflR y
Literature search e.g. PubMed Database search:
U
se
f
u
l

R
esources
y
Database

search:
y
OMIM: Online Mendelian Inheritance in Man, Centre for Medical
Genetics, Johns-Hopkins University (Baltimore, M.D.) and the
National Center for Biotechnology Information, National Library of National

Center

for

Biotechnology

Information,

National

Library

of

Medicine (Bethesda, M.D.). http://www//ncbi-nlm.nih.gov./OMIM/
.
y
LMD: London Medical Databases by Winter R & Baraitser M.
[email protected]
y
POSSUM: Murdoch Childrens Research Institute. http://www.possum.net.au/
NB: Most of the figures included in this presentation are from
personal experience, few figures are retrieved from the
internet.
62