Down syndrome is one of the most common genetic syndromes, occurring in one of 800 to 1,000 live births.¹ In approximately 95 percent of cases, the syndrome is caused by simple trisomy due to nondisjunction (nonsegregation) of chromosome 21 in the formation of the oocyte or spermatocyte. In 4 to 5 percent of cases, the syndrome is caused by a translocation (link) of one chromosome 21 to another, usually a chromosome 14 or the other chromosome 21. The remaining 1 percent of cases are mosaics (more than one cell line) caused by nondisjunction occurring after conception.²

Because Down syndrome is so common, nearly every family physician provides medical care to at least one family with an affected child. The care of the infant or young child with Down syndrome can be complicated and may involve a myriad of immediate and long-term medical problems and psychosocial issues.

Diagnosis of Down Syndrome

BEFORE BIRTH

The sensitivity of multiple marker screening tests for Down syndrome is between 61 and 67 percent.³ While these tests are not routinely recommended, their benefits and drawbacks should be discussed before the pregnancy has reached 15 weeks.

Maternal serum levels of both alpha-fetoprotein and unconjugated estriol are often lower than normal for maternal and gestational age in women who are carrying a fetus with Down syndrome. In contrast, maternal serum levels of beta-human chorionic gonadotropin are often higher than normal. Testing for these three substances, performed in the second trimester, is often referred to as a “triple screen.”⁴ In addition, an ultrasound examination done in the middle of the second trimester can identify some anomalies strongly associated with Down syndrome, such as nuchal translucency, short femurs, cardiac anomalies and duodenal atresia.^5–7 However, parents should understand that these screening tests should not be used for diagnosis.

In women over 35 years of age, the potential for having an infant with a genetic abnormality is great enough to justify the small risks associated with diagnostic prenatal testing. Chorionic villus sampling is performed between nine and 11 weeks of gestation, and amniocentesis is performed at 16 to 18 weeks of gestation. Either procedure yields fetal cells from which chromosomal abnormalities may be identified.

AT BIRTH

The diagnosis of Down syndrome at birth is based on the presence of a constellation of physical features and is confirmed by genetic karyotyping. All infants with this chromosome disorder do not have every feature of the “typical Down-syndrome facies.”In fact, the physical expression of the syndrome is widely variable. Thus, the diagnosis may be missed if too much reliance is placed on finding the typical facies.

Hypotonia is often the first characteristic of Down syndrome that is noticed. This finding should raise the index of suspicion and prompt further assessment. Other features of Down syndrome are listed in Table 1.^8–11 Some of these physical features occur frequently; others occur much less often but are more specific for Down syndrome. A number of these features are common to several different genetic syndromes.

Karyotyping of a newborn with suspected Down syndrome is important for two reasons. First, by confirming the diagnosis, karyotyping provides a degree of closure for the parents. Second, it gives the parents some guidance concerning their risk of having another child with Down syndrome.

Referral to a medical geneticist for counseling is appropriate, because the risk of having a second child with Down syndrome varies with karyotype and maternal age.¹² In cases of translocation, the possibly increased risk of other family members having a child with Down syndrome may need to be explored.

Medical Problems Associated with Down Syndrome

CONGENITAL HEART DEFECTS

Congenital heart defects are present in 40 to 60 percent of infants with Down syndrome.¹³ Consequently, all newborns with the syndrome should have an electrocardiogram and a screening echocardiogram, even if a murmur is not present. The most common anomalies are complete atrioventricular canal defects (60 percent) and ventricular septal defects (32 percent), followed by tetralogy of Fallot (6 percent), ostium secundum atrial septal defect (1 percent) and isolated mitral cleft (1 percent).¹⁴ The long-term prognosis is best when an infant with a cardiac defect is promptly referred to a pediatric cardiologist for medical management to prevent pulmonary hypertension or to a pediatric cardiac surgeon for early surgical repair.¹⁵

GASTROINTESTINAL DEFECTS

Various gastrointestinal defects are also associated with Down syndrome (Table 2).^16.17 An upper gastrointestinal series or a barium enema may be required to diagnose or confirm the specific defects in a newborn with feeding or stooling problems. Immediate surgical intervention may be necessary to correct a gastrointestinal defect. Down syndrome should not be a deterrent to this surgery.

Infants with Down syndrome may also have significant problems with gastroesophageal reflux. Formal evaluation by barium swallow may be necessary. Treatment options include sleeping with the head raised (although evidence is not available showing that this measure helps infants with Down syndrome) and medications such as cisapride (Propulsid).

Constipation, another common problem, can usually be managed with dietary manipulation.

EAR, NOSE AND THROAT PROBLEMS

Because of midfacial malformations that prevent optimal drainage of eustachian tubes and sinuses, older infants with Down syndrome are more susceptible to otitis media, sinusitis and pharyngitis.¹⁸ If an infant's small external canals make it impossible for the family physician to visualize the tympanic membranes, referral to an ear, nose and throat subspecialist may be necessary.

If otitis media, sinusitis or pharyngitis is caused by bacteria, the infection should be treated promptly and aggressively to prevent associated sequelae. These sequelae can include hearing loss, chronic infection, pneumonia, sepsis, endocarditis or congestive heart failure in infants with concomitant heart defects.

Auditory brainstem response testing to evaluate for hearing loss should be performed when an infant with Down syndrome is six months old (if such testing was not done earlier).

Since decongestants may cause tachycardia, they should not be used in infants with heart defects. Fever may cause tachycardia and should be managed appropriately.

ORTHOPEDIC PROBLEMS

Orthopedic problems are also associated with Down syndrome (Table 3).¹⁹ Infants and children with these problems may need to be referred to a pediatric orthopedist, a physical therapist or both. In some situations, surgery may be necessary to preserve function.

Formerly, radiographs of the flexed and extended cervical spine were recommended as screening tests for atlantoaxial instability when children with Down syndrome reach the age of two years or before they undergo general anesthesia. Although screening radiographs are controversial, 13 percent of children with Down syndrome have asymptomatic atlantoaxial instability that should be monitored and that precludes their participation in contact sports.¹⁶

ENDOCRINE DISORDERS

Endocrine disorders, particularly thyroid disease, are more common in infants with Down syndrome. Since the symptoms of thyroid disease often mimic the symptoms generally associated with Down syndrome, a sensitive thyroid-stimulating hormone test should be performed at least yearly.¹⁶

Gonadal dysfunction and growth hormone deficiency are also associated with Down syndrome.²⁰ These problems may require hormonal therapy.

OTHER PROBLEMS

Congenital cataracts occur more frequently in children with Down syndrome than in other children. Consequently, the red (fundus) reflexes should be checked at birth. Consultation with a pediatric ophthalmologist during the first year is necessary to evaluate an infant for ocular problems that may be correctable (Table 4).¹⁷

Transient myeloproliferative disorder (leukemoid reaction) occurs in approximately 10 percent of newborns with Down syndrome.¹⁷ This disorder is extremely rare in other infants. Phenotypically normal infants who exhibit leukemoid reactions within the first two months of life should be evaluated by karyotype for mosaic Down syndrome.

Children who have Down syndrome have a substantially increased risk for both acute lymphoblastic and nonlymphoblastic leukemia (1 percent).¹⁷ The treatment of leukemia is the same in children with Down syndrome as in other children. However, the toxicity of some chemotherapeutic agents is increased in patients with Down syndrome.

Seizures occur in 5 to 10 percent of children with Down syndrome.¹⁷ Generalized tonicclonic seizures are the most common, but myoclonic and hypsarrhythmia types also occur. Seizures are diagnosed and treated similarly in children with and children without Down syndrome.

Dental problems are common in young children with Down syndrome (Table 5).²¹ Thus, proper dental hygiene and preventive care are essential. Children with heart defects who are undergoing dental procedures should be given antibiotic prophylaxis against subacute bacterial endocarditis.

Feeding the Infant with Down Syndrome

An infant with Down syndrome can be breast-fed.^{2,16,17,22–24} Breast milk is generally easier to digest than formulas of all types.²⁴ Furthermore, breast-fed infants have fewer upper and lower respiratory infections, as well as a lower incidence of otitis media,^25–27 atopic diseases and respiratory allergy.²⁸ Breast feeding also enhances oral motor development, which is the foundation of speech.²⁹ The psychologic benefit derived from the bonding of mother and infant can be extremely important at a time when, because of the infant's disability, the mother may be questioning her own adequacy.² Even if the infant is unable to breast feed directly, expressed breast milk given another way may be beneficial for the child's health and the mother's emotional well-being.

Sucking problems related to hypotonia or cardiac defects may make breast feeding initially difficult,²³ particularly in the premature infant. In this situation, the mother can be encouraged to feed the infant expressed milk by other means, such as a nursing supplementer or a bottle, or, occasionally, by gavage (forced feeding, especially through a tube passed into the stomach). After several weeks, the infant's sucking ability often improves, and the infant becomes capable of nursing effectively.²² A nursing supplementer may be used to encourage the infant who has a weak suck.

Occupational therapists, speech therapists, lactation consultants and breast-feeding support groups usually have specific resources for the mothers of infants with Down syndrome. Mothers may find these resources invaluable.

If the breast-feeding infant is not gaining enough weight, consideration should be given to partial supplementation with formula or additional expressed breast milk. A nursing supplementer may also be used to provide additional caloric intake while the infant continues to breast feed.

Many infants with Down syndrome tend to be “sleepy babies” in the early weeks. Consequently, feeding only on demand may be inadequate for both the caloric and the nutritional needs of the infant and stimulation of the mother's milk supply. In this situation, the infant should be awakened to feed at least every three hours, or every two hours if only breast feeding is being used. The mother may need to pump her breasts to stimulate the production of an adequate supply of milk.^22,24

The mother who prefers formula feeding should also be encouraged to awaken her infant at least every three hours to ensure adequate caloric and nutritional intake. Reflux may be reduced by holding the feeding infant in a semiupright position and keeping the bottle appropriately angled to prevent the swallowing of air.

Unless weight gain is a problem or an infant with Down syndrome has a particular medical disorder, no specific formula is currently recommended. Formula additives or gavage feeding may be necessary in infants with very poor weight gain.

The diet of an infant with Down syndrome should be advanced according to the usual schedule for food groups. However, delayed eruption of teeth may put off the introduction of hard solids. Parents should be reminded that a great deal of patience is required to teach a child with Down syndrome to feed from a spoon and to drink from a cup.

Evaluation of Growth in Down Syndrome

Growth parameters should be plotted at each visit. Both standard and Down syndrome growth curves should be used.^30,31 Infants with heart defects are smaller than other children with Down syndrome who are the same age. However, these infants still maintain an adequate rate of growth if their daily caloric intake is sufficient (i.e., up to 200 kcal per kg per day).³² After the cardiac defect has been repaired, parents should be cautioned against continuing the caloriedense diet, as obesity is a significant problem in many older children with Down syndrome.¹⁶

The cause of any significant drop in growth percentile on either the standard or Down syndrome growth curve should be investigated. Undiagnosed heart defects are the most common reasons for failure to thrive in infants with Down syndrome. Leukemia should also be considered. Unexplained weight gain should prompt an investigation for hypothyroidism.

Health Maintenance

Proper immunizations are extremely important, because structural anomalies make infants with Down syndrome more susceptible to upper respiratory and ear, nose and throat infections. All infants with Down syndrome should receive the standard recommended series of immunizations: diphtheria and tetanus toxoids and pertussis vaccine, live oral poliovirus vaccine, Haemophilus influenzae type b polysaccharide vaccine and measles-mumps-rubella combination vaccine.

The hepatitis B vaccine series should be started at birth, whether the child will be living in an institutional setting or at home. This vaccine series is necessary because persons with Down syndrome are at increased risk of developing the carrier state if they are infected with hepatitis B virus.¹⁸

Yearly influenza immunization has been suggested as another means of reducing the incidence of otitis media in infants and children with Down syndrome.³³

Varicella vaccine should be given when children with Down syndrome reach the age of one year. When these children are two years old, the administration of polyvalent pneumococcal vaccine should be considered.

The Committee on Genetics of the American Academy of Pediatrics has formulated guidelines to assist physicians in caring for children with Down syndrome. These guidelines are summarized in Table 6.³⁴

Developmental Assessment

All facets of development, including gross and fine motor skills, language (speech and comprehension), cognitive abilities, and social and adaptive skills, should be evaluated at each visit. Since infants with Down syndrome are at risk for developmental delay, prompt referral (preferably at birth) should be made to an early intervention program.³⁵

Preschool programs for children with special needs include physical, occupational, speech and educational therapies. In these programs, each child receives individualized multisource stimulation. Often included is the total communication concept, which combines signing and oral language.

With appropriate therapy, developmental delay may be minimized, and the child's social quotient may be improved.^35,36 Such training can provide a foundation for mainstreaming the child with Down syndrome in schools and the community.³⁷

Ideally, therapists should be pediatric specialists who have particular knowledge about Down syndrome. Since most infant therapy is play-based and not strenuous, even infants with medical problems can benefit. Consequently, except in extreme circumstances, referral for early intervention should not be delayed until after surgical correction of a heart defect. Indeed, unrepaired ventricular and atrial septal defects without pulmonary vascular occlusive disease are classified as category I (no restrictions) by the American Heart Association.³⁸ However, a therapy session should be curtailed if an infant shows signs of fatigue.

Cognitive function varies tremendously and cannot be predicted at birth. No relationship has been shown between the number of Down syndrome features present in a newborn and later cognitive function. IQs that have been reported for persons with Down syndrome range from low normal to profoundly retarded. However, there are anecdotal reports of children with Down syndrome who have IQs of 135 to 140. Early intervention programs can improve the academic prognosis for children with Down syndrome.³⁷

Psychosocial Issues

There is no good way to inform parents that their much anticipated, presumably normal newborn has Down syndrome. If possible, the mother and father should be together when they are told about their child's condition. The parents may react with shock, denial, anger, grief, fear, acceptance or any combination of these emotions. The physician should acknowledge the parents' feelings and their right to have them.

Except in cases of extreme medical instability, the infant should be present when parents are informed that the child has Down syndrome. The infant should be referred to by name, so that his or her worth as a human being can be stressed. To lessen denial, the physical traits of Down syndrome can be pointed out in the child. However, normal traits and identifiable familial characteristics should also be stressed in order to convey the idea that the infant with Down syndrome is still a child and a family member.

Privacy is important, and the physician and hospital must respect the parents' wishes regarding information given to other family members. All test results, including normal results, should be reported to the parents promptly. Treatments for serious medical problems, such as heart defects and gastrointestinal anomalies, should be discussed, with emphasis placed on the greatly improved outcomes that have been achieved with these procedures in recent years.A telephone call to the nearest university-based children's medical center or the National Down Syndrome Congress can provide the physician with the latest information on treatments and their outcomes.

The mother and father may benefit from an opportunity to meet with the parents of an older child with Down syndrome. Such a meeting may provide tangible proof that a child with Down syndrome can thrive and become a vital part of the family.

Valuable information and support are available from both national organizations and local groups (Table 7). Initially, parents should also receive written patient education and resource information. In addition, they should be given the telephone numbers of various support organizations and encouraged to contact these groups when they feel ready to do so.

The mother and father of a newborn with Down syndrome should be encouraged to take adequate family leave before returning to work outside the home. The most intense bonding between parents and infant occurs in the first few weeks after birth. Bonding time may be especially important for the family of an infant with Down syndrome. Over this period, the new parents can become comfortable providing for the special needs of their child, and they can also begin to develop coping strategies for the future.

When the parents return to work, they may need assistance in finding appropriate day care. Most large day care centers accept children with Down syndrome. However, in these large centers, the infants with congenital heart defects may be at increased risk of infection and resultant congestive heart failure. Alternatives include in-home care or a home day care setting with a smaller number of children. A smaller day care facility can often maintain stricter infection control measures.

The parents may need help in applying for Supplemental Security Income assistance. Legal counseling concerning long-term custody and estate planning may also be appropriate.

Final Comment

Life tables published in 1989 showed that more than 50 percent of infants with Down syndrome could be expected to live more than 50 years.¹ As mortality rates for the operative repair of congenital heart defects continue to decrease, survival may increase considerably.³⁹ Since the trend toward deinstitutionalization began in the 1970s, it has become apparent that the maintenance of optimal health is a major factor in the lifelong functioning of persons with Down syndrome. Primary health care has become essential to helping these persons have longer, more productive lives.