1. GENETIC PRINCIPLES IN
PAEDIATRIC SURGERY

2. Presented By:
Dr. Fariha Hussain
Intern Doctor
Shaheed Suhrawardy Medical College
Hospital

3. Definition of Genetic Disorder
Congenital Anomaly & Birth
Defect
 A Genetic Disorder is an illness
caused by abnormalities in genes or
chromosomes, especially a condition
that is present from before birth.
 A Congenital Anomaly is a physical
abnormality present at birth.
 Birth defects can be defined as
structural or functional abnormalities,
including metabolic disorders, which
are present from birth

4. Note:
 A genetic disorder may or may
not result into a congenital
anomaly
 A congenital anomaly may or
may not be caused by a genetic
disorder
 A congenital anomaly is a
structural abnormality
 A birth defect can be structural

5. Studies have shown that:
 1 to 3% of newborns have a major congenital
anomaly that will affect their quality of life.
 In 1988 Centres for Disease Control (CDC,
USA) reported that birth defects were the
leading cause of infant mortality, primary
cause of infant deaths in 8160 children and
contributing cause in 1000 more.
 50% of all paediatric patients admitted in the
hospital had a disorder with some genetic
component.

6. Classification of Genetic Disorders
 Multifactorial + environment
 Single gene
(Mendelian) Male
 Chromosomal
 Mitochondrial
 Somatic mutations (cancer)

7. Genetic Disorders
 Multifactorial (common)
- “Environmental” influences act on a genetic predisposition to
produce a liability to a disease.
- One organ system affected.
- Person affected if liability above a threshold.
 Single gene (1% liveborn)
- Dominant/recessive pedigree patterns (Mendelian inheritance).
- Can affect structural proteins, enzymes, receptors, transcription
factors.
 Chromosomal (0.6% liveborn)
- Thousands of genes may be involved.
- Multiple organ systems affected at multiple stages in gestation.
- Usually de novo (trisomies, deletions, duplications) but can be
inherited (translocations).

8. Dominant
Heterozygotes with one copy of the altered gene
are affected
Recessive
Homozygotes with two copies of the altered gene are
affected
X-linked recessive
Males with one copy of the altered gene on the
X-chromosome are affected
Male

9. Congenital Malformations
 Causes
 Genetic/chromosomal
 Environmental
 Incidence
 2-3% of newborn (4-6% by age 5)
 In 40-60% of all birth defects cause is
unknown
 Genetic/chromosomal
 10%-15%
 Environmental
 10%
 Multifactorial (genetic & environmental)
 20%-25%

10. Categories of Birth Defects
Birth Defects can be placed
in one of the following
established categories:

11. Categories of Birth Defects:
 Deformation
 Disruption
 Dysplasia
 Malformation
 Association
 Field Defect
 Sequence

12. Deformation
 Have no inherent genetic
basis
 Mechanical forces have
altered the shape of the
structure affected
 Example: Talipes equinovarus
or Clubfoot

13. Club Foot
 Lower limbs were
genetically
programmed to form
normally
 External forces (e.g.
decreased amount
of amniotic fluid) or
Internal forces (e.g.
neurological
impairment)
prevented such
development

14. Disruption
 The genetic programme of the
structure was normal like in
Deformation
 Developmental process was
interrupted by some mechanism,
causing the anomaly
 Example: Anomalies in newborn
exposed to cocaine in utero

15. Cocaine
(Vasoconstrictive agent)
Temporarily restrictied blood suply to the developing
structures
Malformations
Craniofacial anomalies,
Intestinal Atresia
etc.

16. Dysplasia
 A generalized
abnormality at the level
of cellular
organization in a
specific tissue.
 Example: Connective
tissue disorder e.g.
Marfan’s syndrome in
which Fibrillin, a
component of
connective tissue is
absent because of
genetic mutation

17. Malformation
A malformation is an anomaly in which the
developmental process was abnormal
from the outset
 Caused by:
• Genetic Mutation
• Congenital infection
• Teratogen Exposure
 Example: Cleft lip & Palate

18. Cleft Lip and Palate
 Structures
that join the
lip and palate
fail to fuse
normally

19. Syndrome
 A child will have multiple
malformations
 The observed malformations are
pathologically related to a single
cause.
 Example: - Down Syndrome
- Turner’s Syndrome
- Klinefelter’s Syndrome

20. A Child with Down Syndrome( Trisomy

21. Features of Turner’s Syndrome

22. Features of Klinefelter’s Syndrome (47XXY)

23. Association
 An association is a nonrandom
occurrence of a set of malformations that
are not pathologically related
 The malformations in Association occur
more commonly together than separately
 But not caused by the same genetic or
teratogenic insult
 Example: VACTERL Association
CHARGE Association

24. VACTERL Association
 Features
 V - Vertebral anomalies
 A - Anal atresia/
Imperforate Anus
 C - Cardiovascular
anomalies
 T - Tracheoesophageal
fistula
 E - Esophageal atresia
Newborn with radial atresia of the
 R - Renal (Kidney) right arm, is displaying a limb
and/or radial anomalies anomaly included in VACTERL
Association
 L - Limb defects

25. CHARGE Association
 Colobomas Retarded growth
 Heart defects Genital anomolies
 Atresia of the Ear anomalies
choanae
(A) Twin aged 2 months. (B) Twin aged 2 years showing mildly
dysmorphic features with laterally extended eyebrows with medial flare. (C)
A typical CHARGE ear, low set, short, wide, protruding, simplified, and
featureless. The ears were also asymmetric.

26. Field Defect
 A field defect is a set of
malformations that are grouped in a
localized area of body or a so called
developmental field
 An abnormal developmental stimuli
e.g. a teratogen or mutated gene
result in a developmental field defect
 Example: Cloacal Extrophy

27. Cloacal Extrophy
 Includes:
 Lower abdominal wall
defect
 Bladder extrophy
 Sacral vertebral
defects
 Urogenital anomaly
 Caused by abnormal
migration of neural
crest cells in the
caudal area in 4th
week of gestation

28. Sequence
A series of findings that
are derived from a single
anomaly or mechanical
force
Example : Pierre – Robin
Sequence which results in
Pierre- Robin’s Syndrome

29. Pierre – Robin Syndrome
Includes :
 Small Jaw
 A midline, U shaped
cleft palate
 A relatively large
and protruding
tongue

30. Pierre – Robin Sequence
Small
• Primary anomaly
Jaw
Displaceme • Protruding tongue due to
nt of
tongue in
inadequate room
superior
direction
• Development of Pierre –
Cleft
Robin Syndrome from
Palate constellation of the three

31. Genetic Conditions Commonly
Encountered in Paediatriac Surgical
Wards
 Spina Bifida Umbilical hernias
 Congenital Clubfoot
Diaphragmatic Defect Omphalocoele
 Duodenal Atresia Pyloric Stenosis
Tracheoesophagial
 Imperforate Anus
Fistula
 Inguinal Hernia
 Hirschprung’s
Disease

32. Frequently occurring surgical
anomalies with associated genetic
conditions:
1. Congenital Diaphragmatic Defect:
occurs in –
 DiGeorge Syndrome
 Ehlers-Danlos Syndrome
 Marfan’s Syndrome
 Goldenhar Syndrome
 Turner’s syndrome
 Trisomy 13, 18, 21

33. 2. Duodenal Atresia :
 Down’s Syndrome
 Fetal Hydantoin Exposure
 Thalidomide Exposure
 Opitz Syndrome

34. 3. Hirschprung’s Disease:
 Cartilage- hair hypoplasia
 Down’s Syndrome
 Multiple Endocrine Adenomatosis
type3
 Pallister – Hall Syndrome
 Spondylometaphysial Dysplasia

35. 4. Imperforate Anus:
 Baller- Gerold Syndrome
 Cat’s Eye Syndrome
 FG Syndrome
 Opitz Syndrome
 Johanson-Blizzard Syndrome
 VACTERL Association

36. 5. Inguinal Hernia:
 Cutis- Laxa Syndrome
 Ehlers Danlos Syndrome
 Marfan’s Syndrome

37. 6. Omphalocele:
 Cloacal Extrophy Syndrome
 Marshall-Smith Syndrome
 Meckel-Gruber Syndrome
 Sirenomelia
 Skeletal Dysplasias

38. 7. Pyloric Stenosis:
Apert Syndrome
Cornelia de Lange
Syndrome
Fetal Hydantoin Effects
Fetal Trimethadione effects
Trisomy 18, 21

39. 8. Tracheoesophagial
Fistula:
CHARGE association
DiGeorge Syndrome
Opitz Syndrome
VACTERL association
Trisomy 18, 21

40. Assessment of the child with a
congenital anomaly
 A collaborative effort among many
physicians including a clinical
geneticist is required
 Seemingly unrelated problems has to
be unified under one diagnostic
heading
 In planning appropriate therapy, a
surgeon needs to know the prognosis
of certain genetic disorders

41. The initial assessment needs to address certain key
points:
1. Are other organ systems involved? And if
so, what are the associated anomalies?
2. What are the child’s growth parameters,
including height, weight and head
circumference?
3. Is the child neurologically intact or is there
evidence of developmental delay or mental
retardation?
4. Are there abnormal features present e.g.

42. Availavble Tools for the Diagnosis
of a Child with Birth Defects
 Clinical Evaluation:
 Associated anomalies
 Neurologic examinations
 Dysmorphology (Study of abnormal forms)
evaluation
 Dermatoglyphics (Fingerprint pattern)
 Pedigree Analysis
 Literature Search
 Specialized Laboratory Tests:
 Radiography, USG, MRI
 Chromosome analysis
 Molecular tests

43. Prevention and Treatment
Options
Birth Defects can be prevented by:
 Pre-conceptional care & Increasing Folic Acid Intake
 Limiting Exposure to Teratogens and Mutagens:
 Alcohol & Certain drugs
 Radiation
 Tobacco
 Cigarette
 Infection screening during pregnancy
 Genetic Testing During Pregnancy
 Amniocentesis
 Chorionic villus sampling
 Genetic Counselling of the parents

44. Treatment options for a child with Genetic
Birth Defect:
 Mostly surgical correction of the defect:
 Early surgery on the fetus in utero
 Surgical correction after birth
 Other treatments:
 Medical treatment of the associated
problems
 Palliative care (e.g. in case of
Anencephaly)
 Termination of pregnancy in case of
severe birth defects

45. Conclusion
Of course, many birth defects cannot
be prevented; this is especially true of
defects that have a genetic
component. Thankfully, screening
and treatment methods can be
implemented to avoid the
complications of birth defects and
increase an affected child's
possibilities of a better quality of life.