Birth Defects was written for healthcare workers who look after individuals with birth defects, their families, and women who are at increased risk of giving birth to an infant with a birth defect. This book is being used in the Genetics Education Programme which trains healthcare workers in genetic counselling in South Africa. It covers: modes of inheritance, medical genetic counselling, birth defects due to chromosomal abnormalities, single gene defects, teratogens, multifactorial inheritance

1. 3
Down
syndrome
Before you begin this unit, please take the INTRODUCTION TO
corresponding test at the end of the book to
assess your knowledge of the subject matter. You DOWN SYNDROME
should redo the test after you’ve worked through
the unit, to evaluate what you have learned.
3-1 What is Down syndrome?
Down syndrome is the name given to a
Objectives recognisable pattern of clinical features. Signs
of Down syndrome include a typical facial
appearance, intellectual disability, hypotonia
When you have completed this unit you
(floppiness), congenital heart defects and other
should be able to: birth defects. These children can be recognised
• Define Down syndrome. as they all have a similar physical appearance.
• Understand the causes of Down
syndrome. Individuals with Down syndrome can be
• Explain the risk factors for Down recognised clinically.
syndrome.
• List the clinical features and Down syndrome is the correct term for
complications of Down syndrome. this condition although it is often called
• Plan the care of a child with Down Down’s syndrome. The old terms ‘Mongol’
syndrome. and mongolism are not acceptable and are
no longer used. Down syndrome is a typical
• Understand how the risk of having a child
example of a chromosomal disorder.
with Down syndrome can be reduced.
• Recognise an infant or child with Down NOTE The syndrome was first described in
syndrome. 1866 by Dr Langdon Down in London. A
genetic syndrome is a collection of clinical
• Describe how Down syndrome can be
features and birth defects that can be
diagnosed antenatally. recognised as being a consistent pattern.

2. 50 BIR TH DEFECTS
Maternal age Birth prevalence Birth prevalence of all
in years of live born live born infants with
infants with any chromosomal
Down syndrome abnormality
15 1/1000 1/450
20 1/1734 1/36
25 1/1250 1/476
30 1/965 1/385
35 1/386 1/192
36 1/300 1/16
37 1/234 1/127
38 1/182 1/102
39 1/141 1/83
40 1/110 1/66
41 1/86 1/3
42 1/66 1/42
43 1/53 1/33
44 1/40 1/26
45 1/31 1/21
46 1/24 1/16
47 1/19 1/13
48 1/15 1/10
49 1/11 1/8
Figure 3-1: The birth prevalence of Down syndrome and all chromosomal abnormalities in women of
increasing age
3-2 How common is Down syndrome? community) falls rapidly in developing
countries as many affected children die in
Down syndrome occurs in all communities
infancy or early childhood. For example, in
and ethnic groups. In many developing (low
Limpopo Province the prevalence of Down
resourced) countries the birth prevalence
syndrome in children aged two to nine years is
(number of affected infants/1000 live birth)
only 0.74/1000, indicating that 65% of affected
is 2 to 3 per 1000 live births. In industrialised
children have already died by two years of age.
(high income) countries, the birth prevalence
is less than 1.5/1000 live births.
In South Africa the birth prevalence of Down The birth prevalence of Down syndrome in
syndrome is 2.1/1000 live births in the Limpopo South Africa is about two per 1000 live births.
Province (a poor rural area) and 1.8/1000 in
Soweto (a more developed urban area).
The prevalence (number of affected infants
and children per 1000 children in the

3. DOWN SYNDROME 51
3-3 Why is the birth prevalence of Down NOTE The risk of Down syndrome more
syndrome higher in developing countries? than doubles between 30 and 35 years of
age from 1/965 (approximately 1/1000)
The risk of a woman having an infant with to 1/386 (approximately 2.6/1000.
Down syndrome increases as she gets older.
It is especially high once she reaches 35 years. 3-4 Are most infants with Down
Advanced maternal age (AMA) is the term syndrome born to older women?
used to describe pregnant women of 35 years
or older. Yes. In most developing countries where a
higher percentage of pregnant women are
In developing countries a higher percentage of advanced maternal age, most infants with
of pregnant women are of advanced maternal Down syndrome are born to older mothers.
age. They also often do not have access to, In addition, services for prenatal screening,
or use, family planning (contraception), prenatal diagnosis, genetic counselling
prenatal screening, prenatal diagnosis, genetic and selective termination of pregnancy are
counselling and selective termination of often not available. For example, in South
pregnancy. As a result the birth prevalence of Africa more than half of infants with Down
Down syndrome is high. syndrome infants are born to mother aged 35
The exception is China. Because of their one years or older.
child per family policy, women usually choose In industrialised countries, where women
to have their child between 25 and 27 years use contraception and have access to genetic
of age when the risk of Down syndrome is services, a lower percentage of mothers are
low. Therefore, the birth prevalence of Down of advanced maternal age and most infants
syndrome in China is the lowest in the world with Down syndrome (above 60%) are born to
at less than 1/1000 live births. mothers under 35 years of age.
In industrialised countries, women are aware of
their increased risk of having a child with Down 3-5 Is Down syndrome well
syndrome. Therefore, most use family planning known in all communities?
and choose not to fall pregnant once they reach
In industrialised countries, Down syndrome
35 years of age. This lowers the percentage of
is well publicised so that most members of
pregnant women of advanced maternal age and,
the community know about the condition. In
therefore, reduces the birth prevalence of Down
contrast, the condition is not well known in
syndrome in these countries.
many developing communities, who may not
NOTE In industrialised countries the percentage
even have a local name for the condition.
of women of advanced maternal age dropped The lack of awareness of Down syndrome
between 1950 and 1980 with the introduction in many rural communities in South Africa
of oral contraception. With this the birth
results in many affected children being
prevalence of Down syndrome dropped from
2.5 to less than 1.5/1000 live births. In the last undiagnosed. This situation is improving with
20 years more women are having children at education to inform health-care workers and
an advanced age as they choose to have their the community about Down syndrome.
families late for social reasons. Because they have
access to, and use, genetic services the birth NOTE In the early 1990s in Gauteng Province only
prevalence of Down syndrome has remained low. 3% of mothers of infants with Down syndrome
were aware of the condition before the birth
of their infant. By 1997, due to education of the
The risk of having an infant with Down syndrome community and medical and nursing staff, 47%
increases with advanced maternal age. of mothers presenting for advanced maternal
age counselling knew of Down syndrome.

4. 52 BIR TH DEFECTS
1 2 3 4 5
6 7 8 9 10 11 12
13 14 15 16 17 18
19 20 21 22 X Y
Figure 3-2: The appearance of the chromosomes in trisomy 21 (karyotype). Note that there are three instead
of the normal two chromosomes 21.
3-6 What is the cause of Down syndrome?
Down syndrome is caused by the presence of extra
Down syndrome is the commonest chromosome 21 material in the cells of the body.
chromosomal disorder in live born infants. It
is caused by extra material from chromosome About 3% of infants with Down syndrome do
21 being present in the body’s cells. Individuals not have a whole extra chromosome 21 but
with Down syndrome usually have three, an extra piece of a chromosome 21 is added
instead of the normal two, chromosomes (translocated) onto another chromosome.
21 in all body cells. This is called trisomy 21 The total number of chromosomes is
(‘tri’ means three) … because of the extra therefore normal at 46 (but one of the
chromosome 21, each cell now has a total of chromosomes looks longer than usual as
47 chromosomes instead of the normal 46. it has an extra piece of a chromosome 21).
An extra chromosome 21 (non-disjunction This is called translocation Down syndrome.
resulting in trisomy 21) is the cause of Down This may occur for the first time (a new
syndrome in more than 95% of affected mutation) or be inherited from a parent
children. The risk of recurrence is low. who is a balanced translocation carrier. If
inherited then the parents have a high risk in

5. DOWN SYNDROME 53
Parents’ cells
(46 chromosomes)
Abnormal cell Normal cell
division division
Gametes
(ova or sperm)
No. of chromosomes
(24) (22) (23)
in gametes
Zygotes
(fertilised eggs)
Trisomy Monosomy
(47 chromosomes) (45 chromosomes)
Figure 3-3: Non-disjunction to give trisomy 21
future pregnancies for further children with before fertilisation. In this division, each
translocation Down syndrome. ovum or sperm should get 23 chromosomes.
However, in non-disjunction this division is
In the other 2% of infants with Down
incorrect. The chromosomes 21 pair do not
syndrome, only some of their body cells have
separate, as they should. Instead, one gamete
an extra chromosome 21. This is known
(ovum or sperm) gets two chromosomes 21,
as mosaicism. It has the lowest risk for
while the other gets none. In trisomy 21, usually
recurrence in future pregnancies.
the ovum, with two copies of chromosome 21
(instead of one), is fertilised by a normal sperm
Down syndrome is almost always caused by with one copy of chromosome 21. As a result,
trisomy 21. the zygote (the fertilised cell from which the
embryo and fetus will develop) now has three
The appearance of children with Down copies of chromosome 21 (instead of two) with
syndrome is the same whether the extra a total of 47 chromosomes.
chromosome 21 material is due to trisomy,
NOTE Down syndrome usually occurs because of
translocation or mosaicism. non-disjunction in the ovum of the mother (80%).
However, in 20% of people with Down syndrome
3-7 How does trisomy 21 occur? the non-disjunction takes place in the father, and
it is the sperm that has the extra chromosome 21.
Trisomy 21 (having an extra chromosome 21) is
caused by non-disjunction. This is an unequal
sharing of the 46 chromosomes when forming
the ova (eggs) or sperms (i.e. the gametes)

6. 54 BIR TH DEFECTS
3-8 How can one recognise a • Upward slanting eyes with epicanthic
person with Down syndrome? folds (prominent skin folds at the inner
corner of the eyelids).
Infants, children and adults with Down
• A flat nasal bridge.
syndrome, throughout the world, have a
• Relatively big tongue and small, open
similar appearance. They have clinical features
mouth. Therefore, the tongue often
which can be recognised. However, the clinical
protrudes (sticks out of the mouth).
diagnosis of Down syndrome is frequently
2. Head:
missed in infants in South Africa. To prevent
• The head is round with a flat occiput
this, the clinical diagnosis of Down syndrome
(back of the head). This is called
must be based on a complete history and
brachycephaly.
physical examination, and not just looking
• The head circumference is often smaller
for the facial typical appearance. The clinical
than normal.
diagnosis should be confirmed by a blood test.
• The ears are small and may be
NOTE In South Africa, research shows that only
malformed and low set.
16% of newborn infants with Down syndrome 3. Neck:
are diagnosed by health-care workers in the • The neck is short.
hospital or clinic after delivery. Less than 50% • Skin over the back of the neck is loose,
of infants with Down syndrome are diagnosed forming folds.
before six months of age, even though they
have attended clinics for their immunisations.
Children with Down syndrome all look alike.
3-9 What are the main recognisable
features of Down syndrome? 3-11 What are the typical features of the
The main clinical features of Down syndrome hands of a person with Down syndrome?
are: Infants, children and adults with Down
1. Hypotonia (floppy infant). syndrome all have hands that look alike and
2. A typical facial appearance. can easily be recognised. The typical hand
3. Poor sucking and feeding. appearance includes:
4. Abnormalities of the hands and feet. 1. Short, broad hands with short stubby
5. Poor Moro reflex. fingers (brachydactyly).
6. Developmental delay (poor head control 2. Most have a single palmar crease on one or
with head lag, slow to sit when propped up, both hands.
and unable to bear weight on legs). 3. They often have short, incurved small
7. Intellectual disability. fingers (clinodactyly) and may only have a
8. Signs of congenital heart defects. single crease on their little finger.
9. Growth restriction with short stature
(stunting). 3-12 What are the typical features of the
10. A small penis. feet of a person with Down syndrome?
Infants, children and adults with Down
3-10 What are the typical facial appearances
syndrome also have feet that look alike. The
of a person with Down syndrome?
typical features are:
There are a number of abnormalities seen
1. They are short and broad, similar to the
in the face, head and neck of a person with
hands.
Down syndrome.
2. A wide gap between the large and second
1. Face: toe is common (sandal gap).
• A small, round, flat face.

7. DOWN SYNDROME 55
3. A crease extending from the sandal gap 3-15 Are all people with Down
towards the heel is common. This may not syndrome intellectually disabled?
be obvious in children who do not wear
Down syndrome is the commonest genetic
shoes.
cause of developmental delay and intellectual
disability. The milestones of infants and
People with Down syndrome have short, broad children with Down syndrome are slow,
hands and feet. co-ordination is poor, and language and
social development are delayed. They
are all intellectually disabled to a greater
3-13 What are the signs of hypotonia or lesser degree. However, the degree of
in an infant with Down syndrome? intellectual disability varies widely. With
Infants with Down syndrome are floppy early and appropriate encouragement and
(hypotonic) and have a poor Moro reflex. stimulation, the level of intellectual disability
Obvious floppiness (hypotonia) is most can be improved. These children can then be
marked during the first months of life. There mainstreamed into normal schools, although
is head lag and usually an incomplete Moro their progress will be slow and they will need
reflex. Hypotonia is the most consistent sign special attention. When children with special
in Down syndrome. When handled, infants needs, such as Down syndrome, are put in
feel like a rag doll. Mothers often complain normal schools rather than special schools,
when their infants reach four months of age this is called ‘inclusion’. Whenever possible,
and still do not have head or neck control. As this is the educational policy in South Africa.
children with Down syndrome grow older the As adults, people with Down syndrome work
hypotonia becomes less obvious. well and some may find work in the open
labour market or in sheltered employment.
All newborn infants with Down syndrome have South Africa’s new labour laws promote the
hypotonia. employment of people with disability.
Unfortunately, the degree of impaired learning
3-14 Why do infants with Down disability has been exaggerated in the past
syndrome feed poorly? when little effort was made to encourage
these children to reach their developmental
Infants with Down syndrome often have potential. With late or little stimulation,
feeding difficulties during the first weeks of intellectual disability is often severe, further
life. They feed slowly with a poor suck and disadvantaging them and hindering their
have difficulty swallowing due to the relatively integration into society.
big tongue. Feeds may have to be given by
tube or cup at first before they can breastfeed
adequately. Their hypotonia and frequent All people with Down syndrome have some
blocked nose contribute to the feeding degree of intellectual disability.
problems. However, over the weeks their
feeding improves. Heart failure, caused by NOTE The term intellectual disability is
congenital heart defects, may also cause poor preferred to mental retardation.
feeding, and needs to be treated.
3-16 What is the pattern of growth
Poor feeding is common in infants with Down in infants with Down syndrome?
syndrome. Most South African newborns with Down
syndrome are born at term (37 to 42 weeks)
and have an average birth weight of 2700 g,

8. 56 BIR TH DEFECTS
which is less than normal, and a sign that The parents must be fully counselled and
their fetal growth is slower than usual. their consent obtained before arranging a
After birth, infants and children with Down chromosomal analysis. It is very important to
syndrome continue to grow slowly and confirm the clinical diagnosis and identify the
remain shorter than normal (stunted). Weight chromosome pattern (karyotype) to determine
gain is slow in the first months and years but whether the Down syndrome is due to non-
many children with Down syndrome later disjunction, translocation or mosaicism.
become obese. Obesity remains a problem in
adolescence and adulthood.
A chromosome analysis on a blood sample is
NOTE Older children with Down syndrome used to confirm the clinical diagnosis of Down
in rural areas tend not to be obese. This is syndrome.
because the supply of food is limited and
they get adequate exercise as they have to
share the family and household chores. 3-19 When should parents be told
the diagnosis of Down syndrome?
3-17 Who usually makes the clinical It is important to tell the parents the diagnosis
diagnosis of Down syndrome? as soon as possible. The manner in which
they are told and counselled has a major effect
The diagnosis should be made by the nurses
on the way they accept the diagnosis. With
or doctors caring for the infant after delivery.
careful examination, most infants with Down
However, the clinical features can be difficult
syndrome should be diagnosed at birth or
to recognise in the first few days of life.
shortly thereafter.
Some mothers are first to notice that their
newborn infants do not appear normal or
have problems. If the mother is concerned, the
infant must be examined carefully. THE COMPLICATIONS
The way to identify infants and children with OF DOWN SYNDROME
Down syndrome is to make sure you know
and can recognise their clinical features.
Always look for Down syndrome, especially 3-20 What are the major complications
in infants and children of older mothers and of Down syndrome in children?
infants who are floppy. Take a full history and 1. Congenital malformations: Almost 50%
complete a general examination, being certain of infants with Down syndrome have a
to look for hypotonia, a poor Moro reflex, and major congenital malformation. These are
abnormalities of the hands and feet. Confirm a frequent cause of early death.
the diagnosis with a blood test. 2. Recurrent infections: Children with
Down syndrome have poor functioning
3-18 How is the clinical diagnosis of the immune system. This causes
of Down synfrome confirmed? recurrent infection, especially of the upper
respiratory tract and lungs (pneumonia).
By taking a sample of venous blood which
Pneumonia is worsened by a poor ability
must be added to a specially prepared test
to cough due to the hypotonia. Pneumonia
tube. This is then sent to a genetic laboratory
is a common cause of death in children
where a chromosomal analysis will be
with Down syndrome, especially in the
performed. It is important that the correct test
first few years of life.
tube is obtained and the test arranged with the
3. Visual problems: Squint, nystagmus
laboratory before the blood sample is taken.
(horizontal or vertical jerky movements
of the eyes) and short or long sightedness

9. DOWN SYNDROME 57
are common. Cataracts are less common. 3-22 Which are the commonest
Many children with Down syndrome need congenital heart defects in infants
to wear glasses. with Down syndrome?
4. Hearing problems: This is most often
The commonest congenital heart defects that
caused by repeated middle ear infections
occur in infants with Down syndrome include:
with fluid behind the ear drum (in the
middle ear). 1. Endocardial cushion defect: (a hole
5. Hypothyroidism: This can occur at any between the atria and ventricles of the
age in a person with Down syndrome and heart). The commonest congenital heart
is difficult to diagnose. Routine testing at defects in infants and children with Down
birth, six months of age and then yearly syndrome are endocardial cushion defects.
thereafter should be done to screen for 2. Ventricular septal defect: (VSD – a hole in
hypothyroidism. the wall which separates the two ventricles,
the lower two chambers of the heart).
This may be small, which causes little or
Almost 50% of infants with Down syndrome have no clinical problems and closes without
a major congenital malformation. treatment in the first year of life. However,
it may be large, causing severe problems
NOTE Myeloid leukaemia and an unstable in the first weeks of life, including heart
cervical joint in the neck are rare but important failure, repeated episodes of pneumonia and
complications of Down syndrome. They often
failure to thrive. In these children, medical
also have early onset Alzheimer’s disease as
young adults (as early as 25 to 30 years).
and possibly surgical treatment is indicated.
3. Atrial septal defect: (ASD – a hole in the
wall between the atria, the upper two
3-21 What congenital malformations
chambers of the heart).
are important complications of Down
4. Tetralogy of Fallot: This is a complex heart
syndrome in the newborn infant?
defect in which the child is cyanosed (blue).
1. Congenital heart defects: About 45%
Congenital heart defects are the commonest
of infants with Down syndrome have
cause of death in infants and children with
congenital heart defects. They may present
Down syndrome. Therefore, all newborn
with features of heart failure, recurrent
infants with Down syndrome must be carefully
pneumonia, failure to thrive or cyanosis
examined for signs of congenital heart defects.
(blue). Some are detected when a heart
murmur is heard during routine clinical
examination. Congenital heart defects are the commonest
2. Duodenal atresia: These infants have an cause of death in children with Down syndrome.
obstruction in the duodenum (between
the outlet of the stomach and the start NOTE Endocardial cushion, ventricular septal and
of the small intestine). They vomit their atrial septal defects result in excessive blood flow
feeds in the first few days of life and the through the lungs. These congested, oedematous
vomitus is often bile stained. The diagnosis lungs are very susceptible to infections, which are
can be confirmed on an abdominal X- often the cause of death if not correctly treated.
ray, by the presence of what is called a
‘double bubble’ (the dilated stomach and 3-23 What is the life expectancy of
upper duodenum). They must be urgently children with Down syndrome?
transferred for corrective surgery.
The life expectancy varies widely between
Both duodenal atresia and some congenital different countries. In developing countries,
heart defects can be diagnosed by antenatal most children with Down syndrome die
ultrasound examination. during infancy and early childhood from

10. 58 BIR TH DEFECTS
infections and congenital heart defects. and potassium chloride). The child may
In South Africa 65% of infants and young need referral for special investigations to
children with Down syndrome die before the confirm the cardiac diagnosis and to plan
age of two years. In contrast, most children surgery if necessary and available.
with Down syndrome in industrialised Recurrent infections should be treated
countries can be expected to survive into early and vigorously with antibiotics. Iron
adulthood, with many living between 50 to and multivitamin supplements should
60 years of age. Young women with Down also be prescribed.
syndrome are usually fertile while males are Infants and children with Down syndrome
usually infertile. Contraception for them is should be tested for hypothyroidism, and
very important. They have a 50% chance of treated if necessary.
having an infant with Down syndrome. Children with Down syndrome who have
congenital heart defects need protection
against bacterial endocarditis (infection of
CARING FOR CHILDREN the heart valves) after dental care or surgery.
They must receive prophylactic antibiotics
WITH DOWN SYNDROME before and after these procedures.
All infants and children with Down
syndrome should receive routine
3-24 What care is available for infants
immunisations.
and children with Down syndrome?
3. Surgical treatment:
Infants and children with Down syndrome, Surgical repair for some congenital heart
as with all people with congenital disability, defects may be available in paediatric
should be offered the ‘best possible care’ cardiac units.
available for their problems and special needs. Infants and children with Down
This care includes: syndrome who have visual problems,
including squint, nystagmus, cataracts
1. Diagnosis:
and poor vision, should be referred for an
For infants and children with Down
ophthalmological (eye) assessment.
syndrome, as with all persons with birth
Infants and children with Down syndrome
defects, it is important to make and
who have other congenital malformations
confirm a diagnosis as early as possible.
like duodenal atresia will need surgical
This allows for early genetic counselling
correction of these problems. Boys with
to inform parents about the disorder, its
Down syndrome often have undescended
cause and available treatment. It also helps
testes, which may need surgery if
families come to terms with the condition,
undescended after age two years.
and accept and bond with their child. This
4. Neurodevelopmental therapy and
will encourage the parents to begin early
community-based rehabilitation:
treatment and stimulation programmes,
This is a very important part of caring for
to enable the child to reach his or her
children with Down syndrome.
best long-term potential for health,
5. Genetic counselling and psychosocial
development and intellectual ability.
support.
2. Medical treatment:
Infants and children with Down syndrome NOTE The World Health Organisation
have many problems that require medical has recognised that, given the different
treatment. Some of these treatments circumstances of each country, the levels
can be offered in primary health-care of care available for people with congenital
facilities. Heart failure from congenital disability may differ. However, they consider
that at all times the ‘best possible patient
heart defects can be diagnosed and treated
care’ in the circumstances must be offered.
with anti-failure drugs (digoxin, diuretics

11. DOWN SYNDROME 59
The rights of all people with disability are regions with fewer resources, hospitals
protected in the Constitution of South Africa. may only have a physiotherapist and/or an
occupational therapist. A few may also have a
3-25 How can infants and children community-based rehabilitation programme.
with Down syndrome be helped
In South Africa, rehabilitation for infants and
to reach their full developmental
children with disabilities, including Down
and intellectual potential?
syndrome, can be assisted by the use of a
Infants and children with Down syndrome locally produced stimulation programme
develop slowly and all are intellectually called START (Strive Towards Achieving
disabled to some degree. It has been proved Results Together). This was designed to use
that infants and children with Down syndrome cheap, locally available materials and can be
who receive good early neurodevelopment offered by trained local community members.
therapy, love and stimulation from their This programme is of great benefit to infants
parents at home, have a better intellectual and children with Down syndrome.
outcome (IQ) than those put in institutions or
neglected. The earlier they receive intervention NOTE Information on START can be
and stimulation, the better the results. obtained from Sunshine Centre, P O Box
41167, Craighall, 2024. Telephone 011 642
Every effort must be made to keep the child 2005. Internet: www.sunshine.org.za
with Down syndrome in the home with
their families so that they can be given the
opportunity of fulfilling their emotional, PREVENTION
health and educational needs.
Neurodevelopmental therapy includes the
following: 3-26 Can Down syndrome be prevented?
1. Physiotherapy is very useful for infants Yes. There are two approaches for the
who are floppy and have slow motor prevention of Down syndrome. These are:
milestones. It helps these infants and young 1. Primary prevention by trying to stop
children to achieve their motor milestones infants with Down syndrome being
faster. For the best result, referral as young conceived. This pre-conception approach
as possible is recommended. is the preferred method of prevention. It
2. Hearing assessment (audiology) and is based on the knowledge that the risk
speech therapy are important for infants of having an infant with Down syndrome
and children with Down syndrome as they is greatest in women of 35 years of age
have delayed speech development. This or more. If women are made aware of
is worsened by recurrent ear infections Down syndrome and have access to family
which may cause hearing loss. If deafness planning and contraception, they have the
is suspected, a hearing assessment option of completing their families before
should be done. Speech therapy helps the the age of 35 years. In South Africa, up to
development of better speech. Again, early 50% of Down syndrome pregnancies could
referral gives the best results. be prevented in this manner.
3. Occupational therapy can improve fine 2. Prevention based on genetic screening,
motor co-ordination as well as personal prenatal diagnosis of Down syndrome and
and social development. Early assessment genetic counselling. All women aged 35
and therapy give the best results. years or more should be offered screening.
All these forms of neurodevelopmental Ideally screening should be made available
therapy are available in major centres. for all pregnant women.
However, in both rural and urban areas

12. 60 BIR TH DEFECTS
70% of fetuses with Down syndrome can
Down syndrome can be prevented before
be detected by ultrasound examination.
conception by community education and family
Eleven to 13 weeks is also the best time
planning, and in the antenatal period by prenatal to accurately determine gestational age
screening, diagnosis and genetic counselling. by ultrasound examination. Other birth
defects associated with Down syndrome
may also be detected.
SCREENING FOR NOTE Increased thickness of the skin over
DOWN SYNDROME the back of the neck is due to a collection of
fluid (oedema) and is called increased nuchal
translucency. This is strongly associated with a
3-27 How can Down syndrome be number of chromosomal abnormalities, especially
Down syndrome. It is best to screen for nuchal
screened for during pregnancy?
translucency between 11 and 13 weeks gestation.
Screening tests can identify the risk a woman
3. Second trimester ultrasound examination
has of carrying an infant with Down syndrome
of the fetus:
but cannot make a confident diagnosis. There
Fetal ultrasound screening for major
are a number of methods which can identify
congenital malformations is ideally offered
pregnant women at high risk of having an
at 18 to 20 weeks gestation. It may detect
infant with Down syndrome.
malformations associated with Down
1. By identifying all pregnant women of syndrome. Second trimester ultrasound is
advanced maternal age: not commonly available in South Africa.
This should be done at the first antenatal 4. Maternal serum screening during early
visit when pregnancy is first confirmed. pregnancy (the triple test):
Women aged 35 years or more, and before This is best done at 16 weeks (between
24 weeks gestation, should be offered 15 and 18 weeks) and requires that the
genetic counselling, regarding their gestational age is accurately known and
increased risk for an infant with Down confirmed by ultrasound examination. In
syndrome, and the possibility of prenatal the triple test, the concentrations of three
diagnosis, early in pregnancy. Identifying biochemical compounds are measured in
women of advanced maternal age is the mother’s blood. The test results, together
currently the only form of screening test with the gestational age and the maternal
for Down syndrome that can be offered to age, are entered into a computer program
all women in South Africa. Unfortunately to generate a risk for the fetus having Down
it is still not being done in many parts of syndrome. The triple test is not generally
the country. available in the state sector in South Africa.
2. First trimester ultrasound examination of
NOTE If the fetus has Down syndrome, the
the fetus:
concentration of maternal serum alpha-
This is best performed at 12 weeks of fetoprotein (AFP) and unconjugated oestriol
gestation (between 11 and 13 weeks). (uE3) tend to be decreased and human chorionic
The thickness of the skin over the back gonadotropin (hCG) increased. An open neural
of the fetal neck is measured. The skin tube defect will also result in a raised AFP.
thickness is usually increased with Down
5. Maternal serum and ultrasound screening
syndrome. As the ultrasonographer needs
combined in the first trimester:
special training and expensive equipment,
This is best done at 12 weeks (11–13
ultrasound screening is only available to a
weeks). The concentrations of two
limited number of women in South Africa.
biochemical compounds in the mother’s
Ultrasound screening is useful but will not
blood (PPAP-A and hCG) and the
detect all cases of Down syndrome. About

13. DOWN SYNDROME 61
thickness of the skin over the back of the 3-29 What investigations can confirm or
fetal neck are measured. Together with exclude the diagnosis of Down syndrome?
maternal age, these tests can detect up
When the risk of Down syndrome is increased,
to 85% of fetuses affected with Down
the diagnosis of Down syndrome can be
syndrome if entered into a computer
confirmed in 48 to 72 hours using FISH
program. This is the most accurate form
(Fluorescent In-situ Hybridisation) or PCR-
of screening for Down syndrome but only
aneuploidy tests. These tests detect an abnormal
offered in private practice.
number of chromosomes 13, 18, 21, X and Y.
Screening tests are very useful in identifying
Chromosomal analysis will also confirm or
women at high risk of having a fetus with
exclude the diagnosis of Down syndrome
Down syndrome. Unfortunately most of the
and can tell the difference between trisomy,
tests are not available in the state sector in
translocation or mosaicism
South Africa. There is a great need to make
these screening tests widely available to all
women.
GENETIC COUNSELLING
NOTE If the fetus has Down syndrome the
FOR DOWN SYNDROME
concentration of pregnancy-associated
plasma protein A (PAPP A) is decreased and
hCG is increased. The false positive rate with
combination screening is about 5%.
3-30 What genetic counselling is
needed by parents who have a
child with Down syndrome?
Screening tests are very useful to identify women
Genetic counselling is a very important part
at high risk of having a fetus with Down syndrome. of the care of people with Down syndrome
and their family, especially the parents and
3-28 What should be done if siblings. The parents need to be educated and
prenatal screening indicates a informed about:
high risk of Down syndrome?
1. The diagnosis.
If there is an increased risk for Down 2. The cause of Down syndrome. They need
syndrome on genetic screening (advanced to know that Down syndrome is a genetic
maternal age, ultrasound, maternal serum disorder, caused in 95% of cases, by an
screening or a combinations of these), then the extra chromosome 21 (trisomy 21). The
mother (preferably with her partner) should risk of this happening is greater in women
be counselled and offered prenatal diagnosis of 35 years or more.
with amniocentesis at 16 weeks to confirm 3. The clinical features, complications and
or exclude the possible diagnosis of Down prognosis of Down syndrome. Also what
syndrome. A risk of above one in 250 is often treatment is available.
used to define a high risk for Down syndrome. 4. The increased risk for parents of a child
with Down syndrome having another
NOTE Fetal cells can also be obtained by chorionic child with Down syndrome in future
villus (placental) biopsy or cordocentesis (drawing pregnancies. They need to know their
blood from the umbilical cord). Both have options for reducing this risk by genetic
higher complication risks than amniocentesis
screening and for preventing the birth of
and are only offered at a few tertiary centres
and in private practice in South Africa.
another affected child by genetic screening
and prenatal diagnosis.
The parents, family and child with Down
syndrome need to be offered on-going

14. 62 BIR TH DEFECTS
psychosocial support, as with all individuals 21 having an affected infant in future
who have a congenital disability. They suffer pregnancies is 1 in 100 (1%). If the woman
lifelong problems that require lifelong care. is 35 or more years old, the risk is related to
The burden of the disorder and the care is her age and is given as slightly higher than
experienced not only by the affected person, her age-related risk. In future pregnancies she
but also the family, especially parents, should be offered amniocentesis.
brothers and sisters.
If the child has a translocation involving an
extra piece of chromosome 21, then the risk
3-31 Where can parents, who have a child can vary greatly and be very high (100%
with Down syndrome, get support? recurrence risk in some cases), depending
Support, help and reassurance may be on the type of translocation. Therefore, a
obtained from: chromosome analysis for both parents needs
to be known to be able to counsel them
1. Doctors, nurses (especially genetic-trained correctly. A counsellor with proper training
nursing staff), genetic counsellors and and experience should do the counselling.
neurodevelopmental therapists.
2. Teachers in special schools for the The risk for recurrence of mosaic Down
intellectually disabled. syndrome is 1%.
3. Social workers.
4. The Down Syndrome Association and 3-33 What choices does a pregnant
other support groups play an important woman have if she has an increased risk
role in South Africa in helping persons and for an infant with Down syndrome?
their families with Down syndrome. They
If a pregnant woman is at increased risk for
are involved in educating the public, as well
having a child with Down syndrome, she and
as medical and para-medical professions.
her partner should receive genetic counselling.
They also play a major advocacy role
This counselling should fully inform them of
for people with intellectual disability,
what the risks are and the choices available to
including Down syndrome.
them. These include:
Contact details: Down Syndrome Association,
1. To have prenatal diagnosis. This will
P O Box 163, Bedfordview, 2008.
require an amniocentesis to be done
Telephone 011 6159401. Fax: 011 6159406. E to get fetal cells on which to perform
mail address: dssaoffice@icon.co.za chromosomal analysis, FISH or PCR-
aneuploidy. Amniocentesis is offered
Website: www.downsyndrome.org.za
between 16 and 21 weeks. Because this
Addendum C lists the addresses and contact involves inserting a thin needle through
details of the regional offices of the Down the abdominal wall into the uterus, there
Syndrome Association in South Africa. is a risk that the procedure can cause
complications, including a spontaneous
3-32 What is the risk of a woman, with miscarriage, vaginal bleeding or leaking
one child with Down syndrome, having amniotic fluid. This risk is about 1
another child with Down syndrome? in 140 (0.7%) with an experienced
ultrasonographer. The woman should be
This depends on the chromosomal diagnosis informed of this before deciding whether
of the first child with Down syndrome, she wants prenatal diagnosis.
i.e. whether the child has trisomy 21, a 2. She can continue the pregnancy without
translocation or mosaicism. prenatal diagnosis, but knowing and
The risk for a woman less than 35 years understanding the risks for having an
old with an infant or child with trisomy infant with Down syndrome.

15. DOWN SYNDROME 63
3-34 What choices does a woman have table. This is higher than a risk of 1:1250 for
when a confirmed prenatal diagnosis a woman who is 25 years old. Therefore, the
of Down syndrome has been made? risk is at least five times greater at 37 than at
25 years.
If a prenatal diagnosis of Down syndrome
is confirmed, the woman, preferably with
her partner, should urgently receive genetic 2. What is the birth prevalence of
counselling regarding the diagnosis and their Down syndrome in South Africa?
choices. These include: The birth prevalence of Down syndrome in
1. Continuing with the pregnancy. South Africa is about 2 per 1000 live births.
2. In South Africa they may request legal
termination of pregnancy. 3. Why is the prevalence lower
than the birth prevalence of Down
If termination of pregnancy is discussed with syndrome in South Africa?
the parents in the course of prenatal care,
this discussion should be within the limits The prevalence (number of children with
of the legal term of reference of the country. Down syndrome per 1000 children in the
Health-care providers must not give directive community) is lower than the birth prevalence
or coercive advice, are obliged to respect the because so many infants with Down syndrome
religious and moral beliefs of the parents, and die in the first few years of life. In rural areas
should abide by and support their decisions. of South Africa, the prevalence may be one
third the birth prevalence, indicating that two
The legal terms of reference in South Africa thirds of these children die during infancy and
can be found in the Choice of Termination early childhood.
of Pregnancy Act 92 of 1996. Under the Act
women may apply for a termination before
4. Why is the birth prevalence of Down
they are 20 weeks pregnant if the infant will
syndrome lower in industrialised
have a severe mental or physical abnormality.
than in developing countries?
In industrialised countries women are better
With genetic screening and prenatal diagnosis
informed and more aware about the risk of
people are entitled to genetic counselling and Down syndrome in pregnancy with advanced
always have the right of choice. maternal age (AMA). Women, therefore, use
family planning and usually have their infants
before the age of 35 years. Genetic counselling,
CASE STUDY 1 genetic screening, prenatal diagnosis and other
services are also more available and used in
A 37-year-old mother of two normal children industrialised countries.
asks whether she would be at increased risk
of having an infant with Down syndrome if 5. Are most infants with Down
she planned another child. She wants to know syndrome born to older women?
how common Down syndrome is in South Yes, in developing countries such as South
Africa and whether most infants with Down Africa. However, in industrialised countries,
syndrome are born to older women. such as the USA and Europe, most infants
with Down syndrome are born to younger
1. Is this woman at an increased women as the number of infants born to
risk of Down syndrome? women over 35 years is small.
Yes. Because she is older than 35 years. At 37
years, her calculated risk is 1:234 on the risk

16. 64 BIR TH DEFECTS
6. Why is Down syndrome often not 4. What is the pattern of growth in
recognised at birth in South Africa? infants with Down syndrome?
Because both the general community and Most infants with Down syndrome are born
health-care workers are not informed and at term but have a lower birth weight, length
aware of the condition and the typical clinical and head circumference than usual. They
features. This is improving through education. continue to grow slowly after birth. As children,
It is important that the diagnosis is made adolescents and adults they are short and may
and the parents be told the diagnosis and become obese.
counselled as early as possible after birth.
5. What is the life expectancy in
children with Down syndrome in
CASE STUDY 2 an industrialised country?
In industrialised countries many can be
A midwife notices that a newborn infant does expected to survive to between 50 and 60 years.
not appear normal. The mother says the infant However, in a developing country many die in
does not look like her other five children. childhood from infections and congenital heart
The infant has a small, flat face with upward defects. Therefore, the life expectancy varies
slanting eyes, a flat nasal bridge and keeps widely between different countries.
sticking her tongue out. She is also very floppy
and feeds poorly.
CASE STUDY 3
1. Does this infant have the typical facial
appearances of Down syndrome?
A three-month-old infant is brought to a local
Yes. She may also have a flat occiput, small clinic where the diagnosis of Down syndrome
ears and a lot of loose skin over the back of her had been made at birth. The mother says
neck. Some infants with Down syndrome do that the child gets very short of breath and
not have all the typical features. becomes cyanosed (blue) with feeds. She
wants to know whether her child will be able
2. What should the midwife look for if she to attend a normal school.
examines the infant’s hands and feet?
1. What is the probable complication
Both hands and feet are short and broad. The
in this child with Down syndrome?
hands may have a single palmar crease, and
often a short curved little finger with a single It may have a congenital heart defect or
finger crease. There is often a wide gap (sandal pneumonia. Almost 45% of infants with Down
gap) between the first (big) and second toe. syndrome have a congenital heart defect.
Severe and recurrent infections, especially
3. Are infants with Down syndrome chest infections, are common. Congenital
often floppy with poor feeding? heart defects, such as a ventricular septal
defect, often result in pneumonia.
Yes. They are all hypotonic (floppy) with a
poor Moro reflex and head lag. As they grow
2. What other congenital malformation
older the hypotonia improves. Poor feeding
may present in the first days of life?
in the first weeks of life is common in infants
with Down syndrome. This is partly due to Duodenal atresia. This is an obstruction in
the relatively large tongue. Some are unable the duodenum which presents with repeated
to breastfeed at first and may need to be fed vomiting in the first few days of life. The
expressed breast milk by cup. vomitus is often bile stained. They need urgent

17. DOWN SYNDROME 65
referral to hospital for confirmation of the 1. Is an ultrasound examination a reliable
diagnosis and surgery. method of screening for Down syndrome?
Ultrasound examination in early pregnancy
3. Do children with Down syndrome is a very useful method of screening for
have normal intelligence? Down syndrome. Between 11 and 13 weeks of
No. They all have developmental delay and pregnancy, many fetuses with Down syndrome
some degree of intellectual disability. They can be detected (about 70%). Other birth
often also have visual and hearing problems defects may also be diagnosed.
which may interfere with their speech
development. 2. What other tests may be helpful
to screen for Down syndrome?
4. Can they attend a normal school? A maternal serum test (triple test), done
If possible they should attend a normal between 15 and 18 weeks, is very useful.
school. However, they will need special help. Together with maternal age and an ultrasound
Therefore, with an ‘inclusion’ policy, a child examination, these screening tests will identify
with special needs, such as children with up to 85% of fetuses with an increased risk of
Down syndrome, is put into normal school. Down syndrome.
5. How can children with Down 3. What should be done if the
syndrome be helped to reach their full screening tests indicate a high
developmental and intellectual potential? risk for Down syndrome?
They should receive love and early stimulation After counselling, the woman should be offered
at home. Neurodevelopmental therapy, which an amniocentesis at 16 to 21 weeks gestation
is available at most major centres, will help to obtain some fetal cells. FISH and PCR-
them reach their developmental milestones aneuploidy tests can be used to identify trisomy.
sooner and have a better intellectual outcome Chromosomal analysis will also confirm or
(IQ). Community-based rehabilitation exclude the diagnosis of Down syndrome.
programmes should be available for children
with Down syndrome in smaller towns and 4. What should be done if the tests
rural areas. Every effort must be made to meet confirm Down syndrome?
their emotional, health and educational needs.
The woman, preferably with her partner,
should be urgently referred for further genetic
counselling. The diagnosis and implications
CASE STUDY 4 of Down syndrome will be discussed. The
woman will have to consider the choices
A primigravid woman with a 12-week of further management and decide on her
pregnancy attends her first antenatal clinic. option of termination or continuation of her
After receiving the routine antenatal care she pregnancy. The final decision rests with the
has an ultrasound examination. She is asked to couple, who must be assured that their choice
return the next day for further tests. will not influence their future routine care.