Birth Defects: Down syndrome


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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

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Birth Defects: Down syndrome

  1. 1. 3 Down syndromeBefore you begin this unit, please take the INTRODUCTION TOcorresponding test at the end of the book toassess your knowledge of the subject matter. You DOWN SYNDROMEshould redo the test after you’ve worked throughthe 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. 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 1/8Figure 3-1: The birth prevalence of Down syndrome and all chromosomal abnormalities in women ofincreasing age3-2 How common is Down syndrome? community) falls rapidly in developing countries as many affected children die inDown syndrome occurs in all communities infancy or early childhood. For example, inand ethnic groups. In many developing (low Limpopo Province the prevalence of Downresourced) 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 affectedis 2 to 3 per 1000 live births. In industrialised children have already died by two years of age.(high income) countries, the birth prevalenceis less than 1.5/1000 live births.In South Africa the birth prevalence of Down The birth prevalence of Down syndrome insyndrome 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 inSoweto (a more developed urban area).The prevalence (number of affected infantsand children per 1000 children in the
  3. 3. DOWN SYNDROME 513-3 Why is the birth prevalence of Down NOTE The risk of Down syndrome moresyndrome 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 DownAdvanced maternal age (AMA) is the term syndrome born to older women?used to describe pregnant women of 35 yearsor older. Yes. In most developing countries where a higher percentage of pregnant women areIn developing countries a higher percentage of advanced maternal age, most infants withof 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 counsellingprenatal screening, prenatal diagnosis, genetic and selective termination of pregnancy arecounselling and selective termination of often not available. For example, in Southpregnancy. As a result the birth prevalence of Africa more than half of infants with DownDown syndrome is high. syndrome infants are born to mother aged 35The exception is China. Because of their one years or older.child per family policy, women usually choose In industrialised countries, where womento have their child between 25 and 27 years use contraception and have access to geneticof age when the risk of Down syndrome is services, a lower percentage of mothers arelow. Therefore, the birth prevalence of Down of advanced maternal age and most infantssyndrome in China is the lowest in the world with Down syndrome (above 60%) are born toat less than 1/1000 live births. mothers under 35 years of age.In industrialised countries, women are aware oftheir increased risk of having a child with Down 3-5 Is Down syndrome wellsyndrome. Therefore, most use family planning known in all communities?and choose not to fall pregnant once they reach In industrialised countries, Down syndrome35 years of age. This lowers the percentage of is well publicised so that most members ofpregnant women of advanced maternal age and, the community know about the condition. Intherefore, reduces the birth prevalence of Down contrast, the condition is not well known insyndrome 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. 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 YFigure 3-2: The appearance of the chromosomes in trisomy 21 (karyotype). Note that there are three insteadof the normal two chromosomes 21.3-6 What is the cause of Down syndrome? Down syndrome is caused by the presence of extraDown syndrome is the commonest chromosome 21 material in the cells of the body.chromosomal disorder in live born infants. Itis caused by extra material from chromosome About 3% of infants with Down syndrome do21 being present in the body’s cells. Individuals not have a whole extra chromosome 21 butwith Down syndrome usually have three, an extra piece of a chromosome 21 is addedinstead 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 thechromosome 21, each cell now has a total of chromosomes looks longer than usual as47 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 newsyndrome in more than 95% of affected mutation) or be inherited from a parentchildren. The risk of recurrence is low. who is a balanced translocation carrier. If inherited then the parents have a high risk in
  5. 5. DOWN SYNDROME 53 Parents’ cells (46 chromosomes)Abnormal cell Normal celldivision 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 21future pregnancies for further children with before fertilisation. In this division, eachtranslocation Down syndrome. ovum or sperm should get 23 chromosomes. However, in non-disjunction this division isIn the other 2% of infants with Down incorrect. The chromosomes 21 pair do notsyndrome, only some of their body cells have separate, as they should. Instead, one gametean 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, usuallyrecurrence 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 threeThe appearance of children with Down copies of chromosome 21 (instead of two) withsyndrome is the same whether the extra a total of 47 chromosomes.chromosome 21 material is due to trisomy, NOTE Down syndrome usually occurs because oftranslocation or mosaicism. non-disjunction in the ovum of the mother (80%). However, in 20% of people with Down syndrome3-7 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) iscaused by non-disjunction. This is an unequalsharing of the 46 chromosomes when formingthe ova (eggs) or sperms (i.e. the gametes)
  6. 6. 54 BIR TH DEFECTS3-8 How can one recognise a • Upward slanting eyes with epicanthicperson 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, opensimilar appearance. They have clinical features mouth. Therefore, the tongue oftenwhich 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 occiputthis, the clinical diagnosis of Down syndrome (back of the head). This is calledmust be based on a complete history and brachycephaly.physical examination, and not just looking • The head circumference is often smallerfor 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 recognisablefeatures of Down syndrome? 3-11 What are the typical features of theThe main clinical features of Down syndrome hands of a person with Down syndrome?are: Infants, children and adults with Down1. Hypotonia (floppy infant). syndrome all have hands that look alike and2. A typical facial appearance. can easily be recognised. The typical hand3. Poor sucking and feeding. appearance includes:4. Abnormalities of the hands and feet. 1. Short, broad hands with short stubby5. 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 small7. Intellectual disability. fingers (clinodactyly) and may only have a8. 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 the10. A small penis. feet of a person with Down syndrome? Infants, children and adults with Down3-10 What are the typical facial appearances syndrome also have feet that look alike. Theof a person with Down syndrome? typical features are:There are a number of abnormalities seen 1. They are short and broad, similar to thein the face, head and neck of a person with hands.Down syndrome. 2. A wide gap between the large and second1. Face: toe is common (sandal gap). • A small, round, flat face.
  7. 7. DOWN SYNDROME 553. 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 greater3-13 What are the signs of hypotonia or lesser degree. However, the degree ofin an infant with Down syndrome? intellectual disability varies widely. WithInfants with Down syndrome are floppy early and appropriate encouragement and(hypotonic) and have a poor Moro reflex. stimulation, the level of intellectual disabilityObvious floppiness (hypotonia) is most can be improved. These children can then bemarked during the first months of life. There mainstreamed into normal schools, althoughis head lag and usually an incomplete Moro their progress will be slow and they will needreflex. Hypotonia is the most consistent sign special attention. When children with specialin Down syndrome. When handled, infants needs, such as Down syndrome, are put infeel 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 workhypotonia 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 learning3-14 Why do infants with Down disability has been exaggerated in the pastsyndrome feed poorly? when little effort was made to encourage these children to reach their developmentalInfants with Down syndrome often have potential. With late or little stimulation,feeding difficulties during the first weeks of intellectual disability is often severe, furtherlife. They feed slowly with a poor suck and disadvantaging them and hindering theirhave difficulty swallowing due to the relatively integration into society.big tongue. Feeds may have to be given bytube or cup at first before they can breastfeedadequately. Their hypotonia and frequent All people with Down syndrome have someblocked nose contribute to the feeding degree of intellectual disability.problems. However, over the weeks theirfeeding improves. Heart failure, caused by NOTE The term intellectual disability iscongenital 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. 8. 56 BIR TH DEFECTSwhich is less than normal, and a sign that The parents must be fully counselled andtheir fetal growth is slower than usual. their consent obtained before arranging aAfter birth, infants and children with Down chromosomal analysis. It is very important tosyndrome continue to grow slowly and confirm the clinical diagnosis and identify theremain shorter than normal (stunted). Weight chromosome pattern (karyotype) to determinegain 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 inadolescence 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 diagnosisdiagnosis of Down syndrome? as soon as possible. The manner in which they are told and counselled has a major effectThe diagnosis should be made by the nurses on the way they accept the diagnosis. Withor doctors caring for the infant after delivery. careful examination, most infants with DownHowever, the clinical features can be difficult syndrome should be diagnosed at birth orto recognise in the first few days of life. shortly thereafter.Some mothers are first to notice that theirnewborn infants do not appear normal orhave problems. If the mother is concerned, theinfant must be examined carefully. THE COMPLICATIONSThe way to identify infants and children with OF DOWN SYNDROMEDown syndrome is to make sure you knowand can recognise their clinical features.Always look for Down syndrome, especially 3-20 What are the major complicationsin 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 ato look for hypotonia, a poor Moro reflex, and major congenital malformation. These areabnormalities 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 functioning3-18 How is the clinical diagnosis of the immune system. This causesof 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 abilitymust be added to a specially prepared test to cough due to the hypotonia. Pneumoniatube. This is then sent to a genetic laboratory is a common cause of death in childrenwhere a chromosomal analysis will be with Down syndrome, especially in theperformed. It is important that the correct test first few years of is obtained and the test arranged with the 3. Visual problems: Squint, nystagmuslaboratory before the blood sample is taken. (horizontal or vertical jerky movements of the eyes) and short or long sightedness
  9. 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 hole5. 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 two3-21 What congenital malformations chambers of the heart).are important complications of Down 4. Tetralogy of Fallot: This is a complex heartsyndrome 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 commonest2. 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 betweenBoth duodenal atresia and some congenital different countries. In developing countries,heart defects can be diagnosed by antenatal most children with Down syndrome dieultrasound examination. during infancy and early childhood from
  10. 10. 58 BIR TH DEFECTSinfections and congenital heart defects. and potassium chloride). The child mayIn South Africa 65% of infants and young need referral for special investigations tochildren with Down syndrome die before the confirm the cardiac diagnosis and to planage of two years. In contrast, most children surgery if necessary and available.with Down syndrome in industrialised Recurrent infections should be treatedcountries can be expected to survive into early and vigorously with antibiotics. Ironadulthood, with many living between 50 to and multivitamin supplements should60 years of age. Young women with Down also be prescribed.syndrome are usually fertile while males are Infants and children with Down syndromeusually infertile. Contraception for them is should be tested for hypothyroidism, andvery 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 ofCARING FOR CHILDREN the heart valves) after dental care or surgery. They must receive prophylactic antibioticsWITH DOWN SYNDROME before and after these procedures. All infants and children with Down syndrome should receive routine3-24 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 heartas with all people with congenital disability, defects may be available in paediatricshould be offered the ‘best possible care’ cardiac units.available for their problems and special needs. Infants and children with DownThis care includes: syndrome who have visual problems, including squint, nystagmus, cataracts1. 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. 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 a3-25 How can infants and children community-based rehabilitation programme.with Down syndrome be helped In South Africa, rehabilitation for infants andto reach their full developmental children with disabilities, including Downand intellectual potential? syndrome, can be assisted by the use of aInfants and children with Down syndrome locally produced stimulation programmedevelop slowly and all are intellectually called START (Strive Towards Achievingdisabled to some degree. It has been proved Results Together). This was designed to usethat infants and children with Down syndrome cheap, locally available materials and can bewho receive good early neurodevelopment offered by trained local community members.therapy, love and stimulation from their This programme is of great benefit to infantsparents at home, have a better intellectual and children with Down syndrome.outcome (IQ) than those put in institutions orneglected. The earlier they receive intervention NOTE Information on START can beand stimulation, the better the results. obtained from Sunshine Centre, P O Box 41167, Craighall, 2024. Telephone 011 642Every effort must be made to keep the child 2005. Internet: Down syndrome in the home withtheir families so that they can be given theopportunity of fulfilling their emotional, PREVENTIONhealth and educational needs.Neurodevelopmental therapy includes thefollowing: 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. It2. 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 availabletherapy are available in major centres. for all pregnant women.However, in both rural and urban areas
  12. 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 overDOWN 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 a3-27 How can Down syndrome be number of chromosomal abnormalities, especially Down syndrome. It is best to screen for nuchalscreened for during pregnancy? translucency between 11 and 13 weeks gestation.Screening tests can identify the risk a woman 3. Second trimester ultrasound examinationhas of carrying an infant with Down syndrome of the fetus:but cannot make a confident diagnosis. There Fetal ultrasound screening for majorare a number of methods which can identify congenital malformations is ideally offeredpregnant women at high risk of having an at 18 to 20 weeks gestation. It may detectinfant with Down syndrome. malformations associated with Down1. 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. 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 orwomen at high risk of having a fetus with exclude the diagnosis of Down syndromeDown syndrome. Unfortunately most of the and can tell the difference between trisomy,tests are not available in the state sector in translocation or mosaicismSouth Africa. There is a great need to makethese screening tests widely available to allwomen. 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 and3-28 What should be done if siblings. The parents need to be educated andprenatal 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 needsyndrome on genetic screening (advanced to know that Down syndrome is a geneticmaternal age, ultrasound, maternal serum disorder, caused in 95% of cases, by anscreening or a combinations of these), then the extra chromosome 21 (trisomy 21). Themother (preferably with her partner) should risk of this happening is greater in womenbe counselled and offered prenatal diagnosis of 35 years or more.with amniocentesis at 16 weeks to confirm 3. The clinical features, complications andor exclude the possible diagnosis of Down prognosis of Down syndrome. Also whatsyndrome. 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. 14. 62 BIR TH DEFECTSpsychosocial support, as with all individuals 21 having an affected infant in futurewho have a congenital disability. They suffer pregnancies is 1 in 100 (1%). If the womanlifelong problems that require lifelong care. is 35 or more years old, the risk is related toThe burden of the disorder and the care is her age and is given as slightly higher thanexperienced not only by the affected person, her age-related risk. In future pregnancies shebut 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 risk3-31 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), dependingSupport, help and reassurance may be on the type of translocation. Therefore, aobtained from: chromosome analysis for both parents needs to be known to be able to counsel them1. 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 willP O Box 163, Bedfordview, 2008. require an amniocentesis to be doneTelephone 011 6159401. Fax: 011 6159406. E to get fetal cells on which to performmail address: chromosomal analysis, FISH or PCR- aneuploidy. Amniocentesis is offeredWebsite: between 16 and 21 weeks. Because thisAddendum C lists the addresses and contact involves inserting a thin needle throughdetails of the regional offices of the Down the abdominal wall into the uterus, thereSyndrome Association in South Africa. is a risk that the procedure can cause complications, including a spontaneous3-32 What is the risk of a woman, with miscarriage, vaginal bleeding or leakingone child with Down syndrome, having amniotic fluid. This risk is about 1another child with Down syndrome? in 140 (0.7%) with an experienced ultrasonographer. The woman should beThis depends on the chromosomal diagnosis informed of this before deciding whetherof 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 withouttranslocation or mosaicism. prenatal diagnosis, but knowing andThe risk for a woman less than 35 years understanding the risks for having anold with an infant or child with trisomy infant with Down syndrome.
  15. 15. DOWN SYNDROME 633-34 What choices does a woman have table. This is higher than a risk of 1:1250 forwhen a confirmed prenatal diagnosis a woman who is 25 years old. Therefore, theof Down syndrome has been made? risk is at least five times greater at 37 than at 25 years.If a prenatal diagnosis of Down syndromeis confirmed, the woman, preferably withher partner, should urgently receive genetic 2. What is the birth prevalence ofcounselling regarding the diagnosis and their Down syndrome in South Africa?choices. These include: The birth prevalence of Down syndrome in1. 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 DownIf 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 withof the legal term of reference of the country. Down syndrome per 1000 children in theHealth-care providers must not give directive community) is lower than the birth prevalenceor coercive advice, are obliged to respect the because so many infants with Down syndromereligious and moral beliefs of the parents, and die in the first few years of life. In rural areasshould abide by and support their decisions. of South Africa, the prevalence may be one third the birth prevalence, indicating that twoThe legal terms of reference in South Africa thirds of these children die during infancy andcan be found in the Choice of Termination early childhood.of Pregnancy Act 92 of 1996. Under the Actwomen may apply for a termination before 4. Why is the birth prevalence of Downthey are 20 weeks pregnant if the infant will syndrome lower in industrialisedhave 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 inA 37-year-old mother of two normal children industrialised countries.asks whether she would be at increased riskof having an infant with Down syndrome if 5. Are most infants with Downshe 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 SouthAfrica 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 younger1. Is this woman at an increased women as the number of infants born torisk of Down syndrome? women over 35 years is small.Yes. Because she is older than 35 years. At 37years, her calculated risk is 1:234 on the risk
  16. 16. 64 BIR TH DEFECTS6. Why is Down syndrome often not 4. What is the pattern of growth inrecognised at birth in South Africa? infants with Down syndrome?Because both the general community and Most infants with Down syndrome are bornhealth-care workers are not informed and at term but have a lower birth weight, lengthaware of the condition and the typical clinical and head circumference than usual. Theyfeatures. 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 mayand 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 inCASE STUDY 2 an industrialised country? In industrialised countries many can beA 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 indoes not look like her other five children. childhood from infections and congenital heartThe infant has a small, flat face with upward defects. Therefore, the life expectancy variesslanting eyes, a flat nasal bridge and keeps widely between different countries.sticking her tongue out. She is also very floppyand feeds poorly. CASE STUDY 31. Does this infant have the typical facialappearances of Down syndrome? A three-month-old infant is brought to a localYes. She may also have a flat occiput, small clinic where the diagnosis of Down syndromeears and a lot of loose skin over the back of her had been made at birth. The mother saysneck. Some infants with Down syndrome do that the child gets very short of breath andnot have all the typical features. becomes cyanosed (blue) with feeds. She wants to know whether her child will be able2. 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 complicationBoth hands and feet are short and broad. The in this child with Down syndrome?hands may have a single palmar crease, andoften a short curved little finger with a single It may have a congenital heart defect orfinger crease. There is often a wide gap (sandal pneumonia. Almost 45% of infants with Downgap) between the first (big) and second toe. syndrome have a congenital heart defect. Severe and recurrent infections, especially3. Are infants with Down syndrome chest infections, are common. Congenitaloften floppy with poor feeding? heart defects, such as a ventricular septal defect, often result in pneumonia.Yes. They are all hypotonic (floppy) with apoor Moro reflex and head lag. As they grow 2. What other congenital malformationolder the hypotonia improves. Poor feeding may present in the first days of life?in the first weeks of life is common in infantswith Down syndrome. This is partly due to Duodenal atresia. This is an obstruction inthe relatively large tongue. Some are unable the duodenum which presents with repeatedto breastfeed at first and may need to be fed vomiting in the first few days of life. Theexpressed breast milk by cup. vomitus is often bile stained. They need urgent
  17. 17. DOWN SYNDROME 65referral to hospital for confirmation of the 1. Is an ultrasound examination a reliablediagnosis and surgery. method of screening for Down syndrome? Ultrasound examination in early pregnancy3. Do children with Down syndrome is a very useful method of screening forhave normal intelligence? Down syndrome. Between 11 and 13 weeks ofNo. They all have developmental delay and pregnancy, many fetuses with Down syndromesome degree of intellectual disability. They can be detected (about 70%). Other birthoften also have visual and hearing problems defects may also be diagnosed.which may interfere with their speechdevelopment. 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), doneIf possible they should attend a normal between 15 and 18 weeks, is very However, they will need special help. Together with maternal age and an ultrasoundTherefore, with an ‘inclusion’ policy, a child examination, these screening tests will identifywith special needs, such as children with up to 85% of fetuses with an increased risk ofDown syndrome, is put into normal school. Down syndrome.5. How can children with Down 3. What should be done if thesyndrome be helped to reach their full screening tests indicate a highdevelopmental and intellectual potential? risk for Down syndrome?They should receive love and early stimulation After counselling, the woman should be offeredat home. Neurodevelopmental therapy, which an amniocentesis at 16 to 21 weeks gestationis 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 childrenwith Down syndrome in smaller towns and 4. What should be done if the testsrural 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 implicationsCASE STUDY 4 of Down syndrome will be discussed. The woman will have to consider the choicesA primigravid woman with a 12-week of further management and decide on herpregnancy attends her first antenatal clinic. option of termination or continuation of herAfter receiving the routine antenatal care she pregnancy. The final decision rests with thehas an ultrasound examination. She is asked to couple, who must be assured that their choicereturn the next day for further tests. will not influence their future routine care.