Professional Documents
Culture Documents
Dysmorphology
Samia Temtamy* & Mona Aglan**
*Professor of Human Genetics
**Professor of Clinical Genetics
Human Genetics & Genome Research Division
National Research Centre, Cairo, Egypt
O tli
Outline
y Definition of dysmorphology
y Definition of terms routinely used in the description of
birth defects
y Impact of malformations
y The difference between major & minor anomalies
y Approach to a dysmorphic individual:
y Suspicion & analysis
y Systematic physical examination
y Confirmation
C fi ti off di
diagnosis
i
y Intervention
y Summary
2
D fi iti off dysmorphology
Definition d h l
y The term “dysmorphology” was first coined by Dr.
David
D id S
Smith,
ith USA iin 1960s.
1960
y It implies study of human congenital defects and
abnormalities of body structure that originate before
birth.
y The term “dysmorphic” is used to describe individuals
whose physical features
f are not usually found
f in other
individuals with the same age or ethnic background.
y “Dys”
Dys (Greek)
(Greek)=disordered
disordered or abnormal and
“Morph”=shape
3
Definition of terms routinely used in
th description
the d i ti off birth
bi th defects
d f t
y A malformation / anomaly: is a primary defect where
there is
th i a basic
b i alteration
lt ti off structure,
t t usually
ll
occurring before 10 weeks of gestation.
y Examples: cleft palate, anencephaly, agenesis of limb
or part of a limb.
Lumbar myelomeningeocele
5
y Malformation Syndrome: A pattern of features
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. 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
Hands & feet of a patient with Apert syndrome
Down syndrome
Club foot
Prader-Willi syndrome Infant of diabetic mother
7 with caudal regression
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).
8
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
of limbs and talipes deformity.
deformity
Talipes deformity
Multiple joint contractures (arthrogryposis)
9
y Disruption: Destruction of a tissue that was
previously normal. Examples of disruptive agents
include amniotic bands, local tissue ischemia or
hemorrhage.
10
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
T id t h
Trident hand
d
(2)
Characteristic features
off achondroplasia
h d l i
Radiological findings in achondroplasia: Loss of caudal
widening (1), short long bones of lower limbs (2)
11
Impact of malformations
y About 3% of all children born will have a significant
congenital malformation.
malformation
y These congenital malformations are responsible for a
large
g p proportion
p of neonatal and infant deaths.
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 genetic disorder.
12
The difference between major and
minor anomalies
y Major anomalies are severe, impair normal body
function and require surgery for management (e.g.
cleft palate
palate, congenital heart disease
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
clinodactyly…..).
) They occur with variable frequencies
in the normal population.
13
Significance of minor anomalies
Occurrence of single minor anomaly 15% of all newborns
3% have an associated major
anomaly
Occurrence of two minor anomalies Less common
11% have an associated major
j
anomaly
Presence of 3 or more minor Unusual 1%
anomalies 90% have an associated major
anomaly
42% of idiopathic MR have 3 or more 80% of which are minor
anomalies anomalies
14
Approach
pp to a dysmorphic
y p individual
15
1. History:
y Pedigree:
Consanguinity increases the risk for an autosomal
recessive (AR) disorder
16
Male patient with similarly affected male siblings or
maternal male relatives suggests X-linked disorder.
17
Vertical transmission suggests an autosomal dominant
(AD) disorder, specially male to male transmission.
18
History of miscarriages, stillbirths or early neonatal deaths
suggests the possibility of a parental balanced
chromosome rearrangement
rearrangement.
19
y Pregnancy & family history:
y History of uterine malformations or oligohydramnios
may suggestt a possible
ibl aberrant
b t fforce causing
i
malformation.
y Abnormal fetal position or weak fetal movements
suggest abnormal fetal tone.
y Placental morphology may give clue to the diagnosis
(e.g.
(e g large
a ge placenta
p ace a in Beckwith-Wiedemann
ec ede a
syndrome).
y Birth measurements, as symmetrical intrauterine
growth retardation (IUGR) suggests early onset
whereas, asymmetrical IUGR suggests late onset.
20
y Environmental hazards for the fetus:
y IInfectious
f ti agents
t (e.g.
( viruses,
i bacteria,
b t i parasites…)
it )
y Physical agents (e.g. radiation, heat….)
y Drugs & chemicals
y M t
Maternal l factors
f t (e.g.
( diabetes
di b t mellitus,
llit h
hypertension,
t i
phenylketonuria…….)
y P
Previous
i investigations
i ti ti
21
2. Physical examination:
General principles:
y Determine if the feature is a major anomaly, minor anomaly
or a normal variant.
y Compare
p with other familyy members.
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
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
Findings
g that suggest
gg a possible
p underlying
y g etiology:
gy
General
y Short stature (height below -3SD) or tall stature (height above
+3SD) (SD=standard deviation)
23
y Failure to thrive (height & weight below -3SD) or obesity
(weight above +3SD)
24
Specific organ anomalies
Unusual head shape
Dolichcephaly Brachycephaly
Trigonocephaly Plagiocephaly
Microcephaly
Macrocephaly
(Hydrocephalus)
26
Body proportions
e.g. short spine, short limbs or long limbs…
(1) (2)
y Innercanthal distance
e g Hypotelorism (decreased inner canthal distance or
e.g.
hypertelorism (increased inner canthal distance)
28
y P l b l fissures
Palpebral fi (slanting)
( l ti )
Upslanting of palpebral fissures (e.g. Down syndrome)
29
y Palpebral fissures (length)
Short palpebral fissures (the length of the palpebral fissure is
usuallyy equal
q to the distance between the two eyes
y i.e.
innercanthal distance)
Bl h hi
Blephrophimosis
i U il t l microphthalmia
Unilateral i hth l i ((smallll eye))
Heterochromia
Corneal opacity
p y
Albinism
32
y 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)
Short nose
Sh
Heminasal aplasia
Long nose
33
y E
Ears
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)
34
Abnormal shape or size of the ears
Lip pits
Macrostomia Microstomia
36
y Philtrum
e.g. short, long or flat
Short philtrum
L
Long flflatt philtrum
hilt
37
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
39
Cli d t l (incurved
Clinodactyly (i d fingers,
fi usually
ll fifth finger)
fi )
40
R d ti (absence)
Reduction ( b )ddefect
f t
Postaxial polydactyly
(pedunculated post minimus) Complete postaxial polydactyly
42
Polysyndactyly
o ysy dacty y (p
(preaxial
ea a popolydactyly
ydacty y with
t syndactyly)
sy dacty y)
43
Nails & dermatoglyphics
Simian crease
44 Abnormal flexion creases
Oth limb
Other li b anomalies
li
Hypopigmented area
Facial hemangioma on tthe
o e forehead
o e ead
Cutis marmorata
Hemihypertrophy
with multiple skin
nevi
47 Knee pterygium Skin appendages
H i
Hair
Abnormal amount of hair (alopecia, hirsutism, hypertrichosis)
Alopecia
Webbed neck
Short neck
Chest
Abnormal chest shape (e.g. pectus carinatum, pectus
excavatum, short sternum)
Supernumerary nipple
51
Spine
e.g. anencephaly, encephalocele, myelomeningeocele or stigmata
of spina bifida
Anencephaly
Encephalocele
Myelomeningeocele
52
Abnormal joint shape or mobility
53
Joint & bone deformities
U bili l h
Umbilical hernia
i
G t
Gastroschisis
hi i
Hepatosplenomegaly
55
Genitalia
e.g. ambiguous genitalia
Micropenis
Clitromegaly
46,XX DSD
56
II- Confirmation of diagnosis:
Lab. tests:
y I di ti
Indications ffor chromosome
h analysis:
l i
y Multiple congenital anomalies
y Ambiguous genitalia
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
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
III- Intervention:
Treatment:
y Symptoms
S t
y Underlying cause
Counselling:
y Diagnosis, natural history, prognosis, management
y Recurrence risk
y Reproductive
Follow-up:
y Identification and counselling of at risk family members
y S
Surveillance
ill ffor complications
li ti
y Correction of diagnosis
58
Summary
y A congenital anomaly or birth defect is an abnormality of
structure or function that is present at birth
birth.
y Birth defects may be mild or serious.
y The pprinciples
p in dysmorphology
y p gy include the
determination of the underlying pathogenic mechanism
and if it is a single system or multi-system defect.
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
counseling for the parents
parents.
59
Summary (Cont
(Cont.))
y The first step towards an accurate diagnosis of a
syndrome is by extensive phenotypic analysis
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 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
to interpret the results and provide genetic counselling.
counselling
60
U f l Resources
Useful R
y Aase JM. Diagnostic Dysmorphology. Springer, 1990
y Jones KL
KL. Smith’s
Smith s Recognizable Patterns of Human Malformations:
Expert Consult Online and Print. 6th ed. Saunders, 2005
y Gorlin RJ, Cohen MMJr, Hennekam RCM. Syndromes of the Head
and Neck (Oxford Monographs on Medical Genetics) 4th ed.
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. 5th 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
U f l Resources
Useful R
y Literature search e.g. PubMed
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
Medicine (Bethesda, M.D.). http://www//ncbi-nlm.nih.gov./OMIM/.
y LMD: London Medical Databases by Winter R & Baraitser M.
info@lmdatabases.com
y POSSUM: Murdoch Childrens Research Institute.
http://www.possum.net.au/
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