Congenital Abnormality - Complete

Safrina D.
Ratnaningrum
CONGENITAL
DISORDER
CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA
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CONTENTS:
Introduction
Classification
Incidence
Dysmorphology
Factors influence fetal quality
How genes are expressed
Environmental factors
Genetic factors
Minor vs major anomalies
Concepts of defect morphogenesis

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INTRODUCTION
Terminology: Congenital disorder ~
congenital disease ~ congenital anomaly
~ congenital defect
Congenital = at birth; anomaly = irregular

�A structural or metabolic abnormality
of the human body that develops before
birth and present at birth
*) congenital metabolic disease ~ inborn
error of metabolism (IEM) 🡪 genetic,
usually AR
Etiology: genetic and non-genetic
(environment)
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BRIEF HISTORY OF
CONGENITAL DISORDER
1941- 1st well-documented reports of maternal
rubella infection as a cause of cataracts, cardiac
defects and deafness in the offspring
40% of these babies died in early infancy due to
severe cardiac, renal or GI anomalies

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CLASSIFICATION
Based on anatomy system:
Released by WHO
https://icd.who.int/browse10/2016/en#/XVII
�ICD = International Classification of Diseases
Based on causative agent:

Released by NLM NIH, US (National Library of Medicine, National
Institute of Health) 🡪 NCBI, National Center of Biomedical
Information
MeSH (Medical Subject Headings)
https://meshb.nlm.nih.gov/record/ui?ui=D000014:
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CLASSIFICATION (CONT’D)
Based on the treatment required:
�Minor anomaly:
� No treatment is needed
� Common in the normal population 🡪 10%
�Major anomaly:
� Need a surgical or medical
treatment/management
� Birth prevalence 🡪 2-3%
Based on the association with

other diseases:
�Non-syndromic / isolated
�Syndromic: associated with other
diseases/abnormalities

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NOTE:
Many normal individuals may have a couple of minor anomalies
≥ 3 minor:
�Chance of having major abnormality
�Chance of having MR (mental retardation)
�Important clue for dysmorphology
The same birth defect may have different etiologies in different

individuals
�Cleft lip/palate may be caused by chromosome disorder, teratogen exposure, amniotic
band, single gene disorder, or combination/multifactorial

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CLASSIFICATION (CONT’D)
Based on the etiology:
�Genetic
�Non-genetic
Note: 50% congenital abnormality causes is unknown

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INCIDENCE
Spontaneous abortion/miscarriage
�Occur in about 50% conception
� 50% chromosome number abnormality
� 15% during 1st trimester (12 weeks pregnancy) 🡪 85% structural abnormality
� Incl. abnormal blastocyst (poor trophoblast 🡪next menstrual flow), mola hydatidosa, blighted ovum
(anembryonic pregnancy, 50% miscarriage)
Death in perinatal and stillbirth

�Incl. 28 week gestation – 1st week postnatal
�25-30% caused by severe structure abnormality
� Developed country (genetic); developing country (environment)

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INCIDENCE (CONT’D)
Newborn and children
�Minor anomaly: 10% of birth
� >2-3 🡪 risk to lead the major anomaly is about 10-20%
�Major anomaly: 2-3% of birth
� Prognosis dependent 🡪 50% good outcome; 25% disability; 25% death
Death in childhood (caused by major anomaly)

�1st year: 25%
�1-10 y: 20%
�10-15 y: 7,5%

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DYSMORPHOLOGY
GROWTH AND DEVELOPMENT
Growth: physically, starts after fertilization and continues
throughout pregnancy, childhood, and adolescence (18 yo).
Growth 🡪 different parts of the body follows a predictable schedule
during normal development and maturation which is influenced by
genetic and environmental factors.
Any disturbance 🡪 disproportion of physical features
(dysmorphology) and development imbalance.
�Physical measurements is needed 🡪 quantitative

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DYSMORPHOLOGY
Abnormal growth/proportions
Abnormal or unusual features and
birth defects
Abnormal genitalia/puberty
Psychomotor/speech delays, MR
Abnormal neuromuscular function
Blindness or deafness
Metabolic problems
*) ≥3 dysmorphic ~ possible
genetic syndrome
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FACTORS INFLUENCE
FETAL QUALITY
Internal factors:
�Genetics (single gene; chromosomal)
� Race; Family pattern; Age; Sex
External/Enviroment factors:
Prenatally
�Maternal nutrition
�Mechanically: club foot
�Chemical agent (ex.drugs)
�Endocrine disorder
�Radiation: congenital malformation
�Infection: TORCH (Toxoplasmosis, Other (syphilis, varicella-zoster,
parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes infections)
�Blood group incompatibility: erythroblastosis foetalis
�Anoxia embryonal: placental disturbances
�Maternal psychologic disturbances
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HOW GENES ARE
EXPRESSED?
Gene-gene interactions Gene-environment interactions
�Dominant vs recessive �Mutagen
�Codominant �Teratogen (single teratogen may cause
�Polygenic more than one defect)
�Etc. �Disease
�Infection
�Etc.
Nature
vs
Nurture
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ENVIRONMENTAL Congenital Rubella
Syndrome
FACTORS Cytomegalovirus (CMV)

Thalidomide

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CONGENITAL INFECTIONS
Agent Clinical signs
TOXOPLASMOSIS Hidrocephaly
Intracerebral calcifications
chorioretinitis
RUBELLA Cataracts/glaucoma
Hearing loss
CHD
CYTOMEGALOVIRUS Microcephaly
Petechiae
HERPES SIMPLEX Skin lessions
Keratoconjunctivitis
CNS involvement

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CONGENITAL RUBELLA
SYNDROME
Classical triad of Rubella

Deafness
CHD
Cataract

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CMV
Figure. Algorithm showing risk of disabilities associated with congenital

cytomegalovirus infection. (Ely et al. 2000. Evaluation of pregnant women
exposed to respiratory virus. Am Fam Physician.15;61(10):3065-3072.
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Thalidomide tragedy- thalidomide was widely used as a
THALIDOMIDE
sedative during 1958-1962. Severe limb anomalies were
seen in babies born to mothers who took it in 1st trimester
Sakata, Tomoya and James K Chen. “Chemical 'Jekyll and Hyde's: small-molecule inhibitors of developmental signaling
pathways.” Chemical Society reviews 40 8 (2011): 4318-31 .

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Source: Lou, K.-J. SciBX
3(13);
doi:10.1038/scibx.2010.396.
Published online April 1,2010
E3 ubiquitin ligase complex consist of:

CRBN: cereblon
DDB1: damage-specific DNA binding protein1
CUL4A: cullin4A
RBX1: ring-box1 CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA
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Down Syndrome
GENETIC FACTORS Phenylketonuria (PKU)
Ecterodactily

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GENETIC FACTORS
1. 50-60% of spontaneously aborted fetuses have
chromosomal abnormalities
2. 1/3rd of all congenital anomalies are caused by
genetic factors
3. Autosomes and/ or sex chromosomes can be
affected
4. Persons with chromosome abnormalities have
characteristic phenotype- they often look more like
other similarly affected persons than their siblings

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GENETIC FACTOR OF
MALFORMATION/ABNORMALI
TY

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DOWN
SYNDROME
(TRISOMY 21)
An abnormal cell division (meiotic
non disjunction, mitotic non
disjunction) results in an extra full
or partial copy (critical region) of Fig. Karyotyping result 47,XY, +21
chromosome 21.
Laboratory findings and etiology:
1. Classical DS (~95%)
� Ova or sperm aging; fertilization
delay.
2. Translocation (~4%)
� Parental balanced translocation.
3. Mosaicism (~1%)
� Mitotic non disjunction post
fertilization. Fig. Karyotiping result 46, XY, der(14:21),(q10;q10)
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DOWN SYNDROME
CHARACTERISTICS
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PHENYLKETONURIA (PKU)
Autosomal recessive
Can cause mental retardation
Screening for PKU
(Aspartame 🡪 aspartic acid and phenylalanine) CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA
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ECTERODACTILY

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GENETIC SPECIFIC Genetic Heterogeneity
INTERACTION Pleiotrophy

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GENETIC HETEROGENEITY /
ALLELIC HETEROGENEITY
-the presence of a variety of genetic defects which cause the same
disease, often due to mutations at different loci on the same gene
-single phenotype or genetic disorder may be caused by any one of a
multiple number of alleles or non-allele mutations.

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http://www.mjdrdypu.org/text.a
Fig. Bardet Biedl syndrome (a) allelic, (b) non-allelic.
CONGENITAL DISORDER,sp?2014/7/2/198/126341
FACULTY OF MEDICINE BRAWIJAYA
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PLEIOTROPHY
->< genetic heterogeneity
- http://www.nature.com/scitable/to
picpage/Pleiotropy-One-Gene-Ca
n-Affect-Multiple-Traits-569
- Example: Phenylketonuria, the
lack of phenylalanine
hydroxylase, which is convert the
phenylalanine to tyrosine.
- Incl. mental retardation, eczema,
and pigment defects that make
affected individuals lighter
skinned

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MINOR VS MAJOR
ANOMALIES
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MINOR ANOMALY
Mongolian spot ~ Blue spot ~ Congenital
dermal melanocytosis
Melanin containing cells which entrap in the
dermis during their migration from the neural
crest to the epidermis during embryonic
development
Fade with age
Prevalence:
�East Asian 90-95%; East African 80-85%;
Polynesians/Micronesians ~90%; Caucasian 1-10%

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Café au lait spot (=coffee with milk)
Hyperpigmented lesions that vary in color from
light brown – dark brown (giant melanosomes)
≠ congenital melanocytic nevus (brown-black; or
hairy)
Do not fade with age; in some cases present after
birth
Prevalence (newborn):
�0,5% Arabic; 0,4% Chinese; 0,3% Caucasian; 3% Hispanic;
18% African

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Association with NF1
(Neurofibromatosis1)
are met if 2 or more the following
criteria are present:
1. If presence 6 or more ~ NF1 (95%)
2. > 5 mm (prepuberty) and >15 mm (postpuberty)
3. Located in the axillary or inguinal region
4. Family history (+)
Note: High penetrance and
variable expressivity

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CONT... Bifid uvula
Incomplete fusion of the medial nasal and processus
maxillaris
Association with cleft palate
Prevalence: Causasian 1%; Native americans 10%
Polydactyly (pre-axial/post-axial/center)
Usually bones without joint
May be non-syndromic (AD) or syndromic
(multifactorial)
1 in 500 births
Prevalence:
10x more frequent in African

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CONT...
Supernumerary nipple/breast ~ polymastia ~
polythelia
Persistent of fragment of the mammary line (7th
week embryo)
Association with cleft palate
Prevalence:
�Causasian 1%; Native americans 10%
�Male is dominant

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CONT...
Albinism (oculocutaneus albinism, OCA),
AR
1 in 40.000
Mutations of tyrosinase gene (TYR) at
11q14-21

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EAR MALFORMATION
External ear/auricula defect include minor and major abnormalities
Minor, examples:
�auricular pit/appendages; prominent ear
Often associated with other malformation 🡪 clues examination
~ chromosomal syndrome (severe form):
�Low set ear (usually ~ micrognathia);
�microtia

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Auricula/Pinna development
• Auricula development
from the 1st (1-3) and
2nd (4-6) pharyngeal
arches
• Six auricular hillocks
(swelling) on the
dorsal end of
pharyngeal cleft
(A) 🡪 fusion &
progressive dev. (B-
C) 🡪 adult auricle (D)

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CONT…
E. H, heart; NP, nasal placode.
F. The position of the ears
related to the mouth and eyes
(e).
G. External ear nearly complete
by growth of the mandible and
neck region to reach the
permanent position.

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NOTE: DEAFNESS (SEVERE
FORM OF EAR ABNORMALITY)
Defect involve middle and or inner ear

Congenital deafness (1 in 1000-2000 births)
�Genetic factors (50%) 🡪 non-syndromic (80%); syndromic
(20%)
�Acquired/environmental factors (25%), in 7th – 8th month by
Rubella virus, toxoplasmosis, CMV, diabetes,
hypothyroidism
�Unknown cause (25%)

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MAJOR ANOMALY
Cleft lip and/or palate
1 in 1000 of births; male 80%
�Bilateral; unilateral
�midline, usually have brain abnormality and mentally retarded
Fail to close:
�Prominentia nasi media 🡪 cleft lip
�Prominentia maxillaris 🡪 cleft palate

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NEURAL TUBE DEFECT
(NTD)
Types of NTD:
Anencephaly
Encephaloceles
Hydranencephaly
Spina bifida

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1. Anencephaly
�The cephalic end of neural tube fails to
close in 25th day of pregnancy; 1:200.000
�No brain formation
2. Encephalocele ~ cranium
bifidum Herniation of dura
�Protrusion of brain that covering with mater through both
membrane; 1:5000; teratogenic effect the foramen cecum
and the fonticulus
frontalis into the
glabellar region

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TYPE OF
ENCEPHALOCELE
1. Meningocele
2. Encephalomeningocele
Location:
�Frontal 🡪 100% survival rate; common in Southeast
Asia
� Nasofrontal/frontonasal
� Nasoethmoidal
� Naso-orbital
�Occipital 🡪 55% survival rate; common in US
�13-14% involved a chromosomal abnormality

�75% survival have some degree of mental deficit

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3. Hydranencephaly ≠ hydrocephalus
�Hydranencephaly: absence of cerebral hemisphere
and replaced by CSF
�Hydrocephalus: accumulation of CSF in the
ventricles

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4. Spina bifida
Abnormal closure of the neural folds in
the 3rd – 4th weeks of development
1 in 1000 birth
Bifid on procc. spinosus
1. Spina bifida occulta , L4-S1 (affects
~10% of normal people) 🡪 hair
2. Spina bifida cystica:
�Meningocele
�Myelomeningocele

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OMPHALOCELE
Congenital herniation of viscera into the
umbilical cord, covered by peritoneum
1:4000 births
Failure the viscera to retraction from the
physiologically herniated during 6-10th
weeks

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Physiological herniation/primary
intestinal loop (6th week)
270 degree counterclockwise
�90: during herniation
�180: during retraction (return to the abdominal
cavity); 10th week

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GASTROSCHISIS
Herniation of abdominal contents which
are not covered by peritoneum, through
the body wall directly into the amniotic
cavity
Occurs lateral to the umbilicus
1:10.000 births; increase in cocaine use
(young women)
Environmental cause >>

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TABLE. MINOR ANOMALY
Examples Related diseases
Mongolian spot Niemann Pick diseases (lysosomal storage disease 🡪
hepatosplenomegaly 🡪 (AR)
Café au lait Neurofibromatosis 1 (NF1)
Polythelia X
Auricular pit Branchio-oto-renal syndrome 🡪 bilateral renal dysplasia
or bilateral polycystic kidney; hearing loss (50%)
Auricular cyst/fistula
Upslanting eye Down syndrome
Simian creases
Clinodactily
Epicanthal folds
Low set ear DS, Turner syndrome, Patau syndrome
Bifid uvula Cleft palate
Polydactyly Trisomy 18; VACTERL association (Langman)
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TABLE. MAJOR ANOMALY
Examples Related diseases
Atresia ani VACTERL association
Congenital cardiac
defects
Cleft lip/palate Patau syndrome
Omphalocele Patau syndrome, Edward syndrome
Hydrocephalus Chiari malformation
Spina bifida

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CONCEPTS OF DEFECT 1. Individual alterations
of structure/form
MORPHOGENESIS 2. Pattern of
morphologic defects

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INDIVIDUAL ALTERATIONS
OF STRUCTURE/FORM
1. Malformation
2. Disruption
3. Deformation
4. Dysplasia

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1. MALFORMATION
Intrinsically abnormal development process occurring early in
pregnancy
Caused by: genetic, epigenetic, environmental factor (mutagen)
�Polydactyly, cleft lip/palate, heart defects, atresia ani, spina bifida
Normal development
Malformation
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TASK 1:
Describe what mutagen is!
Give the classification of mutagen based on its mechanisms!
Give 5 examples (minimal) of common mutagen and explain how do
they work!

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2. DISRUPTIONS
Extrinsically abnormal developmental process
Caused by: amniotic band, drugs, maternal diseases (DM,
Rubella, etc), teratogen
Relatively isolated/non-syndromic
�Congenital deafness, missing digit or extremities
Normal development
Disruptions

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AMNIOTIC BAND
SYNDROME

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TASK 2:
Describe what teratogen is!
Give the classification of teratogen based on its mechanisms!
Give 5 examples (minimal) of common teratogen and explain how
do they work!

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3. DEFORMATIONS
Normal reaction on an abnormal mechanical force,
usually cause abnormal shape/posture
Caused by: uterine constraint in case oligohydramnion
�Club foot, some form of micrognathia, bowing of legs
Normal development
Deformations

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4. DYSPLASIA
Intrinsic cellular abnormality restricted the growth and development
of tissue
�Local (dysplastic lesions): nevus flammeus, haemangioma
�Systemic: ectodermal dysplasia (abnormal dev. of skin hair, nails,
teeths, or sweat gland; AD/AR/XL)
Normal development
Dysplasia
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Fig. Mother & one child (top) have
Ecterodactily (absence of all or part of one or
Fig. Nevus flammeus more digits), Ectodermal dysplasia (EEC) 🡪
variable expressivity
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Fig. Dilatation of vascular with vary of size, location, and color (pink, red, purple)
and do not undergo

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Fig. Treated haemangiomas
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PATTERN OF MORPHOLOGIC
DEFECTS IN MULTIPLE
ANOMALIES
Development of field defect can through the different pattern:
1. Sequence
2. Syndrome
3. Association A
Intrinsic/extrinsic B
cause
C
D

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1. SEQUENCE
Ex: Pierre Robin sequence, primer: micrognathia
followed by ptosis & cleft palate
Cause X
Cause Y Initiating
event A B
Cause Z
C
A A2
1 D
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2. SYNDROME
Multiple anomalies with unknown mechanism
Ex: Down syndrome, fetal alcoholics syndrome
A
B
Cause
C
D
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3. ASSOCIATION
Group of anomalies that occur more freq. together by
chance
• VATER (VACTERL)
association
Cause a A • Vertebral, Anal, Cardiac,
Trachea, Esophageal, Renal,
Cause b B Limbs anomalies
• CHARGE
Cause c C • Colobomas, Heart, Atresia of
choane, Retarded growth,
Genital, Ear anomalies
Cause d D
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SPECIFIC QUESTIONS
When a child is born with a congenital malformation, the
parents have four specific questions:
Why did this happen to our child?
How will it be treated on a short- and long-term basis?
What is the short- and long-term prognosis?
And finally, can it happen again (ie, will siblings or grandchildren be
affected)?
Genetic or molecular studies of congenital malformations in children
can help answer these questions.

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SUMMARY
Congenital disorder is a structural or functional abnormality of the human
body that develops before birth and present at birth distinction between
minor and major abnormality
Etiology: genetic and non-genetic (environment); different cause can give

same manifestation
Non-syndromic (isolated) abnormality usually non-genetic. In contrast with

syndromic which involve gene or chromosomal abnormality
The structure alterations may through several mechanism: malformation,

disruption, deformition, dysplasia, and through different pattern: sequence,
syndrome, association
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REFERENCES:
Gilbert-Barness E & Debich-Spicer D (2004). Embryo and fetal pathology: color
atlas with ultrasound correlation, Cambridge University Press, Cambridge.
Hennekam RC, Biesecker LG, Allanson JE, Hall JG, Opitz HM, Temple IK, Carey
JC. 2013. Elements of morphology: General terms for congenital anomalies. Am J
Med Genet Part A 161A:2726-2733.
Holmes LB (2012). Common malformations. Oxford University Press, New York.
Kingston HM (2002). ABC of clinical genetics, 3rd ed., BMJ Books, London.
Mueller RF & ID Young (2001). Emery’s elements of medical genetics, 11th
ed.Churchil Livingstone, Milan.
Sadler TW & Langman J (2010). Langman’s medical embryology, 11th ed.
Lippincot Williams & Wilkins, Philadelphia.
Etc.
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‫الر ِحي ِم‬
َّ ‫الر ْح َم ِن‬َّ ‫ِب ْس ِم الل ّ َ ِه‬
)٨( ‫اد َوك ُُّل َش ْي ٍء ِعن ْ َد ُه ِب ِم ْق َد ٍار‬
ُ ‫األر َحا ُم َو َما تَ ْز َد‬
ْ ‫يض‬ ُ ‫ح ِم ُل ك ُُّلأُنْثَى َو َما تَ ِغ‬
ْ َ‫الل ّ َ ُه يَ ْعل َُم َما ت‬
(QS.Ar Ra’d:8) Allah mengetahui apa yang dikandung oleh setiap perempuan, apa yang kurang sempurna dan apa yang
bertambah dalam rahim. Dan segala sesuatu ada ukuran di sisi-Nya.

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JOURNAL PRESENTATION
1. The topic: congenital anomaly/malformation/disorder/disease, and related

topics
2. Journal was published at least 10 years ago
3. Case report is preference; journal review is not recommended
4. Ppt slide will be presented about 15 minutes and to be discussed about 10
minutes
5. The score will be included as formative exams and supports the final
exams
6. Please free to discuss your journal with me before the day of presentation
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TERMINOLOGY IN
CONGENITAL ANOMALIES
1. Malformation: alteration
Anomaly (~notofnormal),
the primary
an
dev.program.
anatomic micros/macros
2. phenotype thatthe
Disruption: represents
breakdown a
substantial departure
of a body (<2.5%)
structure that
from the appropriate
had a normal
reference population.
dev.potential.
�Major or minor
3. Deformation:
�Isolated or syndrome altered
shape or position of a
bodya part
Variant, milddue to aberant
anatomic
phenotypemechanical forces
that represent a
small departuere from the
4. Dysplasia: dynamic
appropriate reference
alteration of cellular/tissue
population (2.5-10%).
constitution.
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Safrina D.

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

Congenital = at birth; anomaly = irregular

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

Based on causative agent:

Based on the association with

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

The same birth defect may have different etiologies in different

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

Note: 50% congenital abnormality causes is unknown

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

Death in perinatal and stillbirth

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

Death in childhood (caused by major anomaly)

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

FACTORS Cytomegalovirus (CMV)

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

Classical triad of Rubella

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

Figure. Algorithm showing risk of disabilities associated with congenital

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

E3 ubiquitin ligase complex consist of:

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

Defect involve middle and or inner ear

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

�13-14% involved a chromosomal abnormality

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA

CONGENITAL DISORDER, FACULTY OF MEDICINE BRAWIJAYA