CHAPTER 42

Well-Child Care for Children With Trisomy 21 (Down Syndrome)

Moin Vera, MD, PhD, and Henry J. Lin, MD

Trisomy 21, or Down syndrome, is the most common genetic cause of intellectual disability in children. Primary care physicians are in a unique position to offer affected children specific health maintenance and anticipatory guidance, help manage intercurrent illness and chronic problems, and apply the latest recommendations for clinical screening based on risks for conditions associated with trisomy 21. Additionally, the general pediatrician has the opportunity to develop rapport with children and families, which is of particular importance because of the complex medical and social implications of raising a child with trisomy 21. An important goal of the well-child visit is to provide children with trisomy 21 and their families with counseling about educational, social, and financial resources and support to ensure a healthy and productive transition into adulthood.

Epidemiology

According to the Centers for Disease Control and Prevention, the prevalence of trisomy 21 is approximately 1 in 700 live births in the United States. It is estimated that trisomy 21 is responsible for up to one-third of all cases of moderate to severe intellectual disability. Trisomy 21 has a male-to-female ratio of 1.3:1.

Ninety-five percent of all cases of Down syndrome are caused by chromosomal nondisjunction, and most of these events occur in oocytes during meiosis. The probability of maternal chromosomal nondisjunction is determined by maternal age. A 25-year-old woman has a 1 in 1,240 risk for having a live baby with Down syndrome, and the risk increases to 1 in 340 at age 35 years and 1 in 98 at age 40 years. It is estimated that approximately one-half of trisomy 21 embryos abort spontaneously. The risk of recurrence of the nondisjunction type of Down syndrome in subsequent pregnancies is 1 in 100 until age 35 years, after which the risk determined by age takes precedence. Other family members generally are not at increased risk of bearing children with this type of Down syndrome.

Recent advances in first and second trimester screening allow prenatal diagnosis of Down syndrome with a sensitivity of 80% to 90%. If a prenatal diagnosis of Down syndrome is made and the general pediatrician is asked to participate in counseling the family, the pediatrician should go over with the family the points listed in Box 42.1.

Clinical Presentation

Newborns, infants, and children with trisomy 21 have a characteristic appearance (Box 42.2). They may exhibit microcephaly, with flattening of the occiput and face. The eyes have an upward slant with prominent epicanthal folds, the ears are small and set low, the nasal bridge is flattened, and the tongue appears large. The feet, hands, and digits are small and stubby (ie, brachydactyly), and the fifth digit may be hypoplastic and turned in (ie, clinodactyly). A single palmar crease and wide spacing between the first and second toes may be evident. After the newborn period, diffuse hypotonia and developmental delay are universally seen.

Pathophysiology

Down syndrome is caused by trisomy 21 resulting from meiotic nondisjunction (approximately 95% of cases), translocation (3%–4% of cases), and mosaicism (1%–2% of cases). A small percentage of affected children have a chromosomal rearrangement resulting in 3 copies of a portion of chromosome 21.

Translocations in an affected child are unbalanced and usually occur between chromosome 21 and another acrocentric chromosome, most commonly chromosome 14 or 15. Approximately 75% of these translocations are de novo rearrangements, and 25% are the result of a familial translocation. In the latter case, a parent may be an unaffected carrier of a balanced translocation involving the long arms of chromosome 21 and another acrocentric chromosome (ie, robertsonian translocation). Thus, if a child is found to have a translocation, parental karyotypes must be assessed because balanced translocation carriers have an increased risk of Down syndrome in future children. Mosaicism implies the presence of 2 cell lines—1 normal and 1 with trisomy 21. As might be expected, children with mosaic Down syndrome are usually affected less severely than children with other types of Down syndrome.

Research has focused on the role of individual genes, such as DYRK1A, in the pathogenesis of Down syndrome. It is expected that in the near future, pharmacologic agents that mitigate the effects of excess expression of such genes will result in new treatments for patients with Down syndrome.

Evaluation

Routine health maintenance for newborns, infants, children, and adolescents with trisomy 21 should include discussion of the same issues of health education, prevention, and counseling that are discussed with other patients and their families. The schedule of health maintenance visits for newborns, infants, and young children with trisomy 21 is essentially the same as that recommended by the American Academy of Pediatrics for other children, whereas older children with Down syndrome should be evaluated annually. Surveillance and anticipatory guidance related to the additional medical and psychosocial conditions common among patients with trisomy 21 is tailored to the main periods in a child’s life: newborn, infancy and early childhood, and older childhood and adolescence.

Newborn Period

Verification of the diagnosis of trisomy 21 is perhaps the single most important focus of the initial family visit. Sometimes the diagnosis has been suspected prenatally because of abnormal biochemical markers and sonographic findings and verified by chorionic villus sampling or amniocentesis (Box 42.1). If no prenatal testing data are available and the diagnosis is suspected based on clinical findings, a karyotype test must be performed while in the nursery and the results reviewed at the 1- to 2-week visit. In some institutions, a fluorescence in situ hybridization test for trisomy 21 may provide a more rapid confirmation of the diagnosis (1–3 days).

Several conditions associated with trisomy 21 are important to identify in the newborn period, including hearing loss, congenital heart disease (most commonly endocardial cushion defect), duodenal atresia, Hirschsprung disease, congenital hypothyroidism, hip dislocation, and ocular anomalies (ie, cataracts, glaucoma, strabismus, nystagmus). Hematologic abnormalities include polycythemia, leukemoid reactions that resemble leukemia but resolve during the first month after birth, and, rarely, leukemia.

History

A feeding history is critical because hypotonia often results in difficulty swallowing (Table 42.1). A history of vomiting may be indicative of gastroesophageal reflux or, less commonly, gastrointestinal malformation. Constipation may be the first indication of Hirschsprung disease or hypothyroidism. A detailed family and social history should also be obtained if this was not done in the hospital.

Physical Examination

A detailed physical examination should reveal some common features of newborns with Down syndrome (Box 42.2). All growth parameters should be recorded and compared with those obtained at birth. The size of the fontanels should be evaluated because of the increased incidence of congenital hypothyroidism in this population.

Bilateral red reflexes and conjugate gaze should be documented to exclude congenital cataracts or strabismus. A careful cardiac examination must be performed, noting any cyanosis, murmurs, irregular heart rates, abnormal heart sounds, or asymmetry of pulses. The abdomen should be palpated for organomegaly or any masses, and patency of the anus should be verified. Ortolani and Barlow maneuvers should be performed for hip laxity. Finally, the newborn should be evaluated for hypotonia.

Laboratory Tests

Karyotyping is an important tool in verifying the diagnosis and assessing the risk of recurrence. Newborn screening laboratory tests must be reviewed, especially hearing evaluations and thyroid screenings. Additionally, a cardiac evaluation for congenital heart disease should be performed, which may include electrocardiography, chest radiography, echocardiography, and formal cardiology referral. A complete blood cell count is indicated to assess for hematologic abnormalities, including leukemoid reaction, transient myeloproliferative disorder (ie, pancytopenia, hepatosplenomegaly, and immature white blood cells), and neonatal thrombocytopenia.

Management

The primary care physician should discuss the increased propensity for respiratory infections in children with Down syndrome. Other important issues to address include those pertaining to available resources for children and families, such as early intervention programs and Down syndrome support groups in the community. Educational materials, such as pamphlets and books, may also be supplied at this time. Upcoming appointments with other physicians and allied health professionals should be reviewed.

^a Lack of expert consensus on evaluation. Some recommend testing every 5 years and others recommend testing only symptomatic individuals.

^b Lack of expert consensus on evaluation.

^c Depending on experience and comfort level of primary care physician.

Infancy and Early Childhood

History

Some additional history-related issues to address include a detailed developmental assessment focusing on progress made since the previous visit, because most affected children have motor and speech delays (see Table 42.1). It is important to review any ancillary services, such as physical, occupational, and speech therapy, in anticipation of school entry. The parent or parents should provide their assessment of the child’s vision and hearing. A history of recurrent respiratory infections is concerning for recurrent otitis media with the associated risk of hearing loss. Many children with trisomy 21 experience constipation. A history of snoring and restless sleep may be indicative of obstructive sleep apnea, and a sleep study may be necessary. Finally, it is extremely important to document any history of neck pain, gait changes, increased clumsiness, or other neurologic symptoms that would be indicative of spinal cord compression resulting from atlantoaxial dislocation.

Physical Examination

All growth parameters should be plotted on growth charts specific to children with Down syndrome (Figures 42.1 and 42.2). Children with trisomy 21 are shorter than other children and may have poor weight gain in their first year. Later in life, obesity unrelated to the syndrome may become a problem. As with routine well-child visits in other infants and children, a complete physical examination should be performed at each patient encounter. Noteworthy aspects of the examination in infants and children with trisomy 21 are presented in Box 42.3. In particular, the ear canals of these children are easily collapsed, making it difficult to visualize the tympanic membrane. In some cases, referral to an otolaryngologist may be necessary for an adequate otoscopic examination. A complete neurologic examination should be performed at each visit, including an assessment of the severity of hypotonia.

Laboratory Tests

Hearing evaluation should be performed annually, starting with the newborn hearing screening. Developmentally appropriate gross visual screening should be performed at each visit in infants between 6 and 12 months of age, and a formal ophthalmologic examination is recommended starting at 6 months of age. Thyroid screening tests should be repeated at 6 and 12 months and then annually.

Children with congenital heart disease should be given antibiotic endocarditis prophylaxis for dental or other procedures. Additionally, these children should be considered for monoclonal antibody therapy against respiratory syncytial virus in the winter.

Children with Down syndrome are at increased risk for autoimmune disorders, such as celiac disease, Graves disease, and type 1 diabetes. Because the signs of celiac disease may be subtle, some pediatric gastroenterologists recommend measuring tissue transglutaminase immunoglobulin A antibodies as well as an immunoglobulin A level, at 2 to 3 years of age and every 5 years thereafter. Current American Academy of Pediatrics recommendations include screening only symptomatic children, however.

Children with Down syndrome have an increased incidence of atlantoaxial instability when screened with routine lateral cervical radiographs with flexion and extension views. Any patient with signs or symptoms of spinal cord compression should be evaluated on computed tomography or magnetic resonance imaging and referred to an orthopedic surgeon or neurosurgeon. The symptomatic child should be kept out of any sports that involve contact or neck extension, such as swimming, gymnastics, and soccer. Experts agree that careful neurologic screening at health supervision visits is a much better predictor of serious injury than cervical radiographs. The current recommendation is to screen only symptomatic children, unless a preparticipation radiograph is required for events, such as the Special Olympics.

Management

Infants with trisomy 21 should undergo all routine screening tests and immunizations. Growth and developmental progress should be reviewed with the parent or parents at the end of each visit, and any concerns or unmet expectations should be addressed at this time. Often the developmental delay associated with trisomy 21 is not apparent to families until an infant is 4 to 6 months of age and not achieving the expected milestones of rolling over or sitting. It should also be emphasized to families that the severity of intellectual disability in trisomy 21 is quite variable, ranging from mild to severe. Social function is not necessarily related to IQ, however. If the child is not already enrolled in an early intervention program, the physician should emphasize to the parent or parents the positive role of such an experience. The availability of support groups for parents and other family members should also be discussed. The role of support groups may be especially beneficial to the patient with both Down syndrome and autism spectrum disorder.

In the early childhood years, plans for preschool attendance and future educational opportunities should be reviewed with the family. The role of discipline and the presence of common behavioral problems, such as temper tantrums and biting, should be assessed in preparation for school entry and socialization. Nutrition should be reviewed, because children with Down syndrome have a reduced basal energy expenditure and are at increased risk for obesity. Nutritional supplements and other alternative medicines have not been proved to have any efficacy in the treatment of patients with Down syndrome.

As is recommended for all children, a dental referral should be made by 1 year of age.

Older Childhood and Adolescence

History

School-age children with Down syndrome should continue to visit their primary care physician at least annually. Educational issues should be discussed, including the Individualized Education Program and transition from school. Specific medical issues to address during the history include visual or hearing deficits; evidence of hypothyroidism (ie, decreased activity, coarse and dry hair, constipation); skin problems, including eczema; and dental problems. A careful nutritional history should also be obtained because of the propensity for obesity, and the child should be closely monitored for signs of obstructive sleep apnea.

Figure 42.1. Curve comparisons for weight in kilograms and length in centimeters for male and female subjects, birth to 36 months of age. Contemporary curves from the Down Syndrome Growing Up Study (DSGS [solid line]) are compared with those from the US 1988 curves from Cronk et al (dotted line) and the UK 2002 curves from Styles et al (dashed line).

Reprinted with permission from Zemel BS, Pipan M, Stallings VA, et al. Growth charts for children with Down syndrome in the United States. Pediatrics. 2015;136(5):e1204–e1211.

Physical Examination

The physician should continue to plot height and weight measurements. The skin should be examined closely for xerosis, acne, or syringomas (ie, multiple papules, often present on the eyelids and upper cheeks) during adolescence. A cardiac examination is important because of an increased risk of mitral valve prolapse and val-vular dysfunction. The sexual maturity rating (ie, Tanner stage) of all patients should be noted and discussed with the parent or parents. A pelvic examination is not indicated as a part of the routine visit unless concern exists for sexual abuse or a sexually transmitted infection; however, a testicular examination is important because of the increased risk for testicular cancer in patients with Down syndrome. Patients who participate in sports and other physical activities should undergo a complete neurologic examination to assess for signs of impending atlantoaxial dislocation.

Figure 42.2. Curve comparisons for weight in kilograms and height in centimeters for male and female subjects, 2 to 20 years of age. Contemporary curves from the Down Syndrome Growing Up Study (DSGS [solid line]) are compared with those from the US 1988 curves from Cronk et al (dotted line) and the UK 2002 curves from Styles et al (dashed line).

Reprinted with permission from Zemel BS, Pipan M, Stallings VA, et al. Growth charts for children with Down syndrome in the United States. Pediatrics. 2015;136(5): e1204–e1211.

Laboratory Tests

Annual thyroid screening for thyroid-stimulating hormone and thyroxine levels is recommended for all school-age children and adolescents with trisomy 21, in addition to other routine screening tests. Hearing evaluation should also occur at least once in older children and annually thereafter. Because of the risk of keratoco-nus, an annual ophthalmologic consultation should be conducted after the age of 10 years. Additionally, the child with trisomy 21 should be encouraged to continue biannual dental visits, because gingivitis, periodontal disease, and bruxism (ie, teeth grinding) are common in these individuals.

Management

The major part of the visit with school-age and adolescent children should focus on developmental, educational, and vocational anticipatory guidance. Educational placement and future goals should be developmentally appropriate for the child and acceptable to the parent. Activities requiring socialization and development of responsibility should continue to be encouraged; however, these events can be very stressful for parents and other family members. Injury prevention should be highlighted as well, especially because older children are becoming more independent. In early adolescence, prevocational and vocational training within the school curriculum should be reviewed. Additionally, brief discussions about independent living, group homes, transition of medical care, and financial resources (eg, community-supported employment for young adults) should begin during adolescence.

Stay updated, free articles. Join our Telegram channel

Join