Chromosomal abnormalities occur when there is an abnormal number or structure of chromosomes and can result in congenital disorders. Some common abnormalities include trisomies like Down syndrome which is caused by an extra copy of chromosome 21, and monosomies like Turner syndrome caused by missing one sex chromosome. Other abnormalities involve chromosomal translocations or deletions. Early diagnosis and treatment that addresses medical, developmental, and educational needs can help those with chromosomal disorders reach their highest potential.

1. CHROMOSOMAL ABNORMALITIES
PREPARED BY
JANNET REENA PURANI

2. INTRODUCTION
The process of reproduction (when the ova and sperms are
made, fertilised and divide after conception) is not always
perfect. Abnormalities can occur in the chromosomes and
they may result in a child with a congenital disorder. These
chromosome abnormalities are mostly sporadic, i.e. due to
chance.

3. MECHANISM
If a whole chromosome or part of a chromosome is gained or lost
in the process of reproduction, then the zygote that results will be
abnormal as its genetic plan will have more or less genetic
information than it should have. Later the abnormal embryo may
abort spontaneously or result in an infant with a congenital
disorder. Chromosomal disorders usually present with multiple
abnormalities, including an abnormal appearance (dysmorphic
features), developmental and growth delay and malformations. As
most chromosomal abnormalities are not inherited, the risk of more
than one child being affected (recurrence) is low.

4. CLASSIFICATION
An abnormal number of
chromosomes in the cells
Trisomy
Monosomy
Mosaicism
An abnormal structure of
chromosomes in the cells
Translocation
Deletion

5. NON- DISJUNCTION
This occurs during the formation of the gametes (ova or
sperms) when a pair of the parent’s chromosome does not
split normally. Instead of one chromosome of a pair going
to each gamete, one gamete gets both the paired
chromosomes, and therefore has 24 chromosomes, while
the other gamete does not get a copy of that chromosome
and, therefore, only has 22 chromosomes. This abnormal
process of cell division, which results in two abnormal
gametes, is known as non-disjunction.

7. THE COMMON TRISOMIES ARE:
• Trisomy 21 or Down syndrome (i.e. 47,XY+ 21 or 47,XX+21).
• Trisomy 18 or Edward syndrome (i.e. 47,XY +18 or 47,XX+18).
• Trisomy 13 or Patau syndrome (i.e. 47,XY+ 13 or 46,XX+13).
• XXY in a male called Klinefelter syndrome (i.e. 47,XXY).
• Trisomy X in a female (i.e. 47,XXX).
• XYY in a male (i.e. 47,XYY).
Down syndrome, with trisomy of chromosome 21, is the most common form of
chromosomal congenital disorder.

8. MONOSOMY
•The only chromosome that can be lost and result in
a live born infant with monosomy is a sex
chromosome X or Y. Therefore, the only monosomy
seen is Turner syndrome (i.e. 45,X).

9. MOSAICISMIn the normal zygote there are 46
chromosomes. The zygote then begins dividing by
mitosis to form the embryo which contains many
cells. This division of the one-celled zygote results in
a doubling of cells to 2, 4, 8, 16, 32 cells and so on,
with all the cells having 46 chromosomes. However, in
mosaicism, an error occurs in the zygote. Early on in
this dividing process one of the cells is involved in
non-disjunction resulting in one cell having 47
chromosomes (trisomy) and the other cell only 45
chromosomes (monosomy). The monosomy cell
usually dies but the trisomy cell may survive and
divide. All future cells that come from it will be
trisomy cells. Therefore, the embryo, fetus and infant
that result will have some cells which are normal with
46 chromosomes and other cells which are abnormal
with 47 chromosomes. This is called mosaicism (the
presence of 2 different cell lines of the same genetic
origin in a person).

10. VARIATIONS
INHERITED
DE NOVO
SOMATIC

11. CHROMOSOME TRANSLOCATION
Translocation occurs when a piece of one chromosome breaks off and joins
(translocates) onto another chromosome. If in this process no genetic material is lost
or gained, this is called a ‘balanced’ translocation and the person is clinically normal.
However, if chromosome material is lost or gained then this is an ‘unbalanced
translocation’ and the person will be abnormal because their genetic plan has lost or
gained genetic material.
Persons with balanced translocations are at risk of passing on the abnormal
chromosomes to their offspring, resulting in abnormal embryos with unbalanced
translocations. This can be the cause of recurrent spontaneous abortions. If the
embryo survives, the resulting infant will be abnormal. This risk varies according to
the type of translocation.

13. TYPES

14. CHROMOSOME DELETION
This occurs when a piece of a chromosome, big or small, is missing. There
are several recognized syndromes in which a known piece of chromosome is
missing. These include:
• Prader Willi syndrome with deletion of a specific piece of chromosome 15.
• Deletion 22 syndrome with deletion of a specific piece of chromosome 22.
• Cri du chat (cry of a cat) syndrome with loss of a piece of the small arm of
chromosome 5.

15. Prader Willi syndrome Cri du chat syndrome

16. DOWN SYNDROME
Down syndrome is the commonest chromosomal disorder in
live born infants. It is caused by extra material from chromosome
21 being present in the body’s cells. Individuals with Down
syndrome usually have 3, instead of the normal 2, chromosomes
21 in all body cells. This is called trisomy 21 (‘tri’ means three)
because of the extra chromosome 21, each cell now has a total of
47 chromosomes instead of the normal 46. An extra chromosome
21 (non-disjunction resulting in trisomy 21) is the cause of Down
syndrome in more than 95% of affected children.

18. SIGNS AND SYMPTOMS
• Hypotonia (floppy infant).
• A typical facial appearance.
• Poor sucking and feeding.
• Abnormalities of the hands and feet.
• Poor Moro reflex.
• Developmental delay (poor head control with head lag, slow to sit when propped up, and
unable to bear weight on legs).
• Intellectual disability.
• Signs of congenital heart defects.
• Growth restriction with short stature (stunting).
• A small penis.

19. TYPICAL FACIAL APPEARANCES OF A
PERSON WITH DOWN SYNDROME
Face:A small, round, flat face.
• Upward slanting eyes with epicanthic folds (prominent
skin folds at the inner corner of the eyelids).
• A flat nasal bridge.
• Relatively big tongue and small, open mouth.
Therefore, the tongue often protrudes (sticks out of
the mouth).

21. CONTD..
Head:
• The head is round with a flat occiput (back of the
head). This is called brachycephaly.
• The head circumference is often smaller than
normal.
• The ears are small and may be malformed and low
set.
Neck:
• The neck is short.
• Skin over the back of the neck is loose, forming folds.

22. CONTD..
• The typical hand appearance includes:
• Short, broad hands with short stubby fingers
(brachydactyly).
• Most have a single palmar crease on one or
both hands.
• They often have short, incurved small fingers
(clinodactyly) and may only have a single
crease on their little finger.

23. CONTD..
• The typical features of feet are:
• They are short and broad, similar to the
hands.
• A wide gap between the large and second toe
is common (sandal gap).
• A crease extending from the sandal gap
towards the heel is common. This may not be
obvious in children who do not wear shoes.

24. COMPLICATIONS OF DOWN
SYNDROME
• Congenital malformations: Congenital heart defects, Duodenal atresia
• Recurrent infections: especially the upper respiratory tract and lungs (pneumonia).
• Visual problems: Squint, nystagmus (horizontal or vertical jerky movements of the
eyes) and short or long sightedness are common. Cataracts are less common.
• Hearing problems
• Hypothyroidism: This can occur at any age

25. DIAGNOSIS
• Early Diagnosis: genetic counselling to inform parents about the disorder, its cause and
available treatment. It also helps families come to terms with the condition, and accept and
bond with their child. This will encourage the parents to begin early treatment and
stimulation programmes, to enable the child to reach their best long-term potential for
health, development and intellectual ability.
• Infants and children with Down syndrome should be tested for hypothyroidism, and
treated if necessary.
• Screening:
• By identifying all pregnant women of advanced maternal age
• Ultrasound examination of the fetus
• Maternal serum screening during early pregnancy (the triple test)
• The diagnosis of Down syndrome can be confirmed in 48 to 72 hours using FISH (Fluorescent
In-situ Hybridisation) or PCR-aneuploidy tests. These tests detect an abnormal number of
chromosomes 13, 18, 21, X and Y.
• Chromosomal analysis will also confirm or exclude the diagnosis of Down syndrome and can tell
the difference between trisomy, translocation or mosaicism.

26. CARING FOR CHILDREN WITH DOWN SYNDROME
• Medical treatment:
• Heart failure from congenital heart defects can be diagnosed and
treated with anti-failure drugs (digoxin, diuretics and potassium
chloride).
• plan surgery if necessary
• Recurrent infections should be treated early and vigorously with
antibiotics. Iron and multivitamin supplements should also be
prescribed.
• They must receive prophylactic antibiotics before and after these
procedures to prevent bacterial endocarditis.
• All infants and children with Down syndrome should receive routine
immunisations.

27. CONTD..
• Surgical treatment
• Surgical repair for some congenital heart defects may be available in paediatric cardiac
units.
• Infants and children with Down syndrome who have visual problems, including squint,
nystagmus, cataracts and poor vision, should be referred for an ophthalmological (eye)
assessment.
• Infants and children with Down syndrome who have other congenital malformations like
duodenal atresia will need surgical correction of these problems. Boys with Down
syndrome often have undescended testes, which may need surgery if undescended after
they reach 2 years of age.

28. CONTD..
• Neurodevelopmental therapy and community-based rehabilitation: It has been
proven that infants and children with Down syndrome who receive good early
neurodevelopment therapy, love and stimulation from their parents at home, have a
better intellectual outcome (IQ) than those put in institutions or neglected. The
earlier they receive intervention and stimulation, the better the results.
Neurodevelopmental therapy includes the following:
Physiotherapy
Hearing assessment (audiology) and speech therapy
Occupational therapy can improve fine motor co-ordination as well as personal and
social development

29. PREVENTION
There are two approaches for the prevention of Down syndrome:
• Primary prevention by trying to stop infants with Down syndrome being
conceived. This pre-conception approach is the preferred method of
prevention. It is based on the knowledge that the risk of having an infant
with Down syndrome is greatest in women of 35 years of age or more. If
women are made aware of Down syndrome and have access to family
planning and contraception, they have the option of completing their
families before the age of 35 years.
• Prevention based on genetic screening, prenatal diagnosis of Down
syndrome and genetic counselling. Ideally screening should be made
available for all pregnant women.

30. OTHER CONGENITAL ABNORMALITIES

31. TRISOMY 18 (EDWARDS’ SYNDROME)
These infants have an extra chromosome 18 and present at
birth with multiple, severe physical abnormalities. Most fetuses
(80%) with trisomy 18 miscarry (spontaneously abort) or are
stillborn. Liveborn infants usually only survive for a few days or
weeks. Rarely they may live for a few months. As for Down
syndrome, the risk of a woman having an infant with trisomy 18
increases as she gets older
The diagnosis may be made by antenatal ultrasound
scanning.

32. FEATURES
These infants can be recognised at birth as they are
Growth restricted,
Have a typical face,
Clenched hands,
Overlapping fingers,
Rocker bottom feet or club feet
Very small finger nails.
There are severe abnormalities of the brain, heart and other organs.

34. MANAGEMENT
Management includes counselling and supporting the family,
and palliative care for the infant. Keep the infant warm and
comfortable, Affected infants usually need to be tube fed. It is
uncommon for the mother to have another infant with trisomy 18.

35. TRISOMY 13 (PATAU SYNDROME)
These infants have an extra chromosome 13. It is
slightly more common in older mothers and can be
recognised at birth (but rarely is in SA). Like trisomy 18,
miscarriage and stillbirth are common and most liveborn
infants die soon after birth. The diagnosis may be made
by antenatal ultrasound scanning.

37. FEATURES & MANAGEMENT
Most infants have an abnormal face and brain. The eyes
are usually close together and a cleft lip and polydactaly (extra
fingers) are present. Often there are major abnormalities of the
heart and other organs.
Infants with trisomy 13 often have holoprosencephaly where the
forebrain does not develop fully and the division of the brain into left
and right hemispheres is incomplete. They may have a single ventricle in
the brain.
Management is the same as for trisomy 18. It is unlikely that
the mother will have another infant with trisomy 13.

38. KLINEFELTER SYNDROME
Infants with Klinefelter syndrome are males with an
extra X chromosome (46,XXY). They usually appear
clinically normal at birth but may have undescended
testes or hypospadius. They grow into tall adults with a
high pitched voice, little body hair, immature genitalia,
infertility and learning problems. Life expectancy is
normal. Management is male hormone replacement at
puberty. About 1 in 1000 male infants have Klinefelter
syndrome but the diagnosis is often missed.

40. TURNER SYNDROME
These infants are female with only one X
chromosome (45,XO). Turner syndrome is not
more common in older women as it is usually
the father’s X chromosome that is lost. Almost
all XO fetuses spontaneously abort. The birth
prevalence is 0.5 per 1000. The range and
severity of abnormalities varies between affected
infants. Some infants with Turner syndrome are
mosaic (46,XX/45,X0).

41. TYPICAL CLINICAL FEATURES
• Stunting
• A broad webbed neck
• Low set ears
• Wide spaced nipples
• Puffiness of the hands and feet
• Wide carrying angle of their elbows.
• Amenorrhoea, the absence of a menstrual period
• They may also have abnormalities of their heart and other organs.
• Most have learning difficulties
• All have no ovaries. As a result puberty is delayed and they are sterile.

43. DIAGNOSIS
• Amniocentesis or chorionic villus sampling during pregnancy.
• Abnormal ultrasound findings
• Abnormal triple or quadruple maternal serum screen.
• A test called a karyotype, also known as a chromosome analysis, analyzes the
chromosomal composition of the individual. This is the test of choice to diagnose
Turner syndrome.

44. MANAGEMENT
• Female hormone replacement at puberty if diagnosis occurs early enough
• Estrogen replacement therapy can promote development of the breasts and hips
• Human growth hormone injections during childhood may increase adult height