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Management of Down syndrome
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Literature review current through: Mar 2012. | This topic last updated: Apr 16, 2012.

INTRODUCTION — Down syndrome (DS) is the most common chromosome abnormality among liveborn infants. It is the most frequent form of intellectual disability (mental retardation) caused by a microscopically demonstrable chromosomal aberration.

The Committee on Genetics of the American Academy of Pediatrics (AAP) has provided recommendations to assist clinicians in the care of children with DS [1]. These recommendations are available at pediatrics.aappublications.org/content/128/2/393.full.pdf+html. The recommendations for medical evaluation are summarized in Appendix 1 of this document. Management requires an organized approach to the initial and ongoing evaluation and monitoring for associated abnormalities and prevention of common disorders [2,3].

The management and life expectancy of children with Down syndrome is presented here. The epidemiology, clinical features, and diagnosis are discussed separately. (See "Overview of prenatal screening and diagnosis of Down syndrome", section on 'Candidates for prenatal screening and diagnosis' and "Cytogenetic abnormalities in the embryo, fetus, and infant", section on 'Trisomy 21 (Down syndrome)' and "Clinical features and diagnosis of Down syndrome".)

General issues related to management of adults with intellectual disability are discussed in detail separately. (See "Primary care of the adult with intellectual disability (mental retardation)".)

GROWTH — Anthropometric measurements should be plotted on standard National Center for Health Statistics or World Health Organization growth charts. Patients with DS should be monitored for disturbances of growth associated with other disorders, such as hypothyroidism or celiac disease, and for excessive weight gain. (See "Measurement of growth in children".)

Obesity prevention — A goal of growth monitoring is the prevention of obesity. Interventions beginning at 24 months of age should include attention to diet and promotion of physical activity. Caloric intake should be less than recommended for age in typical individuals, and supplemental vitamins and minerals should be provided [4]. Calcium and vitamin D intake should be monitored closely to minimize bone loss, since adults with DS have lower bone mineral density than controls [5,6].

CARDIAC DISEASE — All newborns with DS should be evaluated for congenital heart disease in consultation with a pediatric cardiologist. An echocardiogram is recommended to detect abnormalities that may not be symptomatic or apparent on physical examination. Continued clinical cardiac evaluation is needed because of the high risk of mitral valve prolapse and aortic regurgitation in adolescents and young adults [2]. In a large retrospective cohort study of congenital heart surgery, patients with DS had similar mortality, but higher morbidity, compared with patients without DS [7]. (See "Congenital heart disease (CHD) in the newborn: Presentation and screening for critical CHD" and "Management and outcome of isolated atrial septal defects in children" and "Management of isolated ventricular septal defects in infants and children" and "Management of patent ductus arteriosus" and "Overview of the management of tetralogy of Fallot".)

HEARING — Newborns should have a newborn hearing screen with brainstem auditory evoked response (BAER) or otoacoustic emission (OAE) [1]. Infants with DS should have repeat hearing screening at six months of age. Hearing should be evaluated regularly throughout childhood, typically every six months until four to five years of age and then yearly. Any child who fails screening should be referred to an otolaryngologist for further evaluation and management. (See "Screening the newborn for hearing loss" and "Evaluation of hearing impairment in children" and "Screening tests in children and adolescents", section on 'Hearing screen'.)

Children should be evaluated and treated for otitis media, which occurs commonly [1]. (See "Acute otitis media in children: Epidemiology, microbiology, clinical manifestations, and complications".)

OPHTHALMOLOGIC DISORDERS — An ophthalmologic assessment should be performed in the newborn period or at least before six months of age to detect strabismus, nystagmus, and cataracts. The risk of refractive errors is approximately 50 percent between three and five years of age [1]. Affected children should have annual assessments of vision. Unaffected children should be examined annually before age five years to detect refractive errors that may occur during childhood, and every two years after age five (every three years after age 13) to screen for disorders, including keratoconus and lens opacities, that may develop in adolescents or adults. The examination should be performed by a pediatric ophthalmologist or ophthalmologist with expertise in infants with disabilities. (See "Visual development and vision assessment in infants and children" and "Evaluation and management of strabismus in children", section on 'Evaluation' and "Overview of nystagmus" and "Cataract in children".)

THYROID FUNCTION — Thyroid function testing should be obtained in the newborn period. The AAP recommends that screening should be repeated at 6 and 12 months, and then annually [1]. However, there is debate regarding the optimal frequency of laboratory screening [8-11]. Height and weight should be measured yearly since the combination of deceleration of linear growth associated with weight gain is a sensitive indicator of hypothyroidism [10]. (See "Clinical features and detection of congenital hypothyroidism".)

CELIAC DISEASE — Screening for symptoms of celiac disease should begin at one year of age [1]. Laboratory screening is recommended if signs or symptoms develop. (See "Clinical manifestations and diagnosis of celiac disease in children".)

HEMATOLOGY — A complete blood count and differential should be obtained at birth to evaluate for myeloproliferative disorders and polycythemia. Infants with transient myeloproliferative disorders should be followed with a complete blood count and differential every three months until three years of age and then every six months until six years of age. This monitoring protocol is modified from that used in the prospective study of transient leukemia in DS conducted by the Pediatric Oncology Group [12]. Children with DS are at increased risk for leukemia. Thus, there should be vigilance for signs of leukemia, such as anemia, increased infections, and excessive bruising. (See "Clinical features and diagnosis of Down syndrome", section on 'Hematologic disorders' and "Neonatal polycythemia" and "Overview of the presentation and classification of acute lymphoblastic leukemia in children".)

A hemoglobin level should be obtained annually from 1 to 13 years of age to screen for anemia [1]. The anemia is usually due to iron deficiency secondary to the restricted diet that many children with Down syndrome develop as a result of delayed oral motor skills and dysphagia. However, anemia may also be a sign of leukemia.

PERIODONTAL DISEASE — Periodontal disease is common in children and adults with DS and involves inflammation, periods of acute infection, and pain [13]. The increased frequency is thought to be due in part to alterations in mouth flora, with a higher frequency of Actinobacillus actinomycetemcomitans compared to controls [14]. Overlapping teeth, poor oral hygiene, and immune deficiency may also play a role [15]. (See "Overview of gingivitis and periodontitis in children and adolescents", section on 'Periodontitis' and "Systemic conditions associated with periodontal disease in children", section on 'Down syndrome'.)

Routine brushing should be encouraged. Dental visits are recommended every six months. Orthodontic problems, which occur in the majority of DS patients, should be evaluated and treated if possible. However, the cooperation necessary for many orthodontic procedures may make them impractical in this population.

ATLANTOAXIAL INSTABILITY — The American Academy of Pediatrics Committee on Genetics and the AAP Committee on Sports Medicine and Fitness recommend careful neurologic evaluation for signs and symptoms consistent with spinal cord injury (eg, loss of motor skills, loss of bowel or bladder control, neck pain, neck stiffness) as the most important clinical predictor of symptomatic atlantoaxial instability and dislocation [1,16]. The evaluating clinician should take a careful history and perform a thorough physical examination, looking for evidence of neurologic involvement. This clinical screening process should be done at least annually. Caution regarding contact sports and trampoline use should be discussed with families. The AAP Committee on Genetics recommends obtaining radiographs for evidence of atlantoaxial instability (AAI), or subluxation, in patients with myopathic signs or symptoms [1]. The AAP Committee on Sports Medicine and Fitness recommends that symptomatic children have an MRI to clarify the extent of spinal cord compression, and that appropriate surgical consultation be obtained to evaluate the need for definitive treatment [16].

Nearly all people with AAI who have suffered a catastrophic injury to the spinal cord have had preceding neurologic symptoms [16]. Asymptomatic AAI is relatively uncommon, occurring in only 2.6 percent of patients with Down syndrome in one study [17]. Despite this, the Special Olympics requires screening neck radiographs in children with DS before participation. Children who are found to have AAI on these radiographs but who lack neurologic symptoms should be followed closely with repeat neurologic examinations (at least annually) [16].

BEHAVIOR AND PSYCHIATRIC PROBLEMS — Assessment and treatment of behavior and psychiatric problems should be expeditious and should include evaluation of the problem at school and at home, behavior management techniques, and medication as needed. (See "Developmental and behavioral screening tests in primary care" and "Attention deficit hyperactivity disorder in children and adolescents: Clinical features and evaluation", section on 'Evaluation'.)

SLEEP APNEA — Children with DS have an increased risk of obstructive sleep apnea because of soft tissue and skeletal alterations that lead to upper airway obstruction. Symptoms related to sleep apnea (snoring, restless sleep, and sleep position) should be discussed at health supervision visits beginning at age one year and continuing throughout childhood [18]. Polysomnography is recommended in all children with DS by four years of age [1]. (See "Mechanisms and predisposing factors for sleep related breathing disorders in children" and "Evaluation of suspected obstructive sleep apnea in children" and "Management of obstructive sleep apnea in children".)

ALZHEIMER DISEASE — Dementia that resembles Alzheimer disease is more common and occurs at an earlier age in patients with DS. A medical evaluation should be performed, including testing for thyroid disease, when the diagnosis of Alzheimer disease is considered. Possible depression should also be excluded. (See "Clinical features and diagnosis of Down syndrome", section on 'Dementia/Alzheimer disease' and "Evaluation of cognitive impairment and dementia" and "Treatment of dementia".)

LIFE EXPECTANCY — Life expectancy in DS is shorter than that in the general population or in individuals with other causes of intellectual disability. However, survival has improved substantially [19,20]. This is illustrated by a study using United States death certificates, in which the median age at death increased from 25 to 49 years from 1983 to 1997 [19]. Compared to death certificates without a diagnosis of DS, those with DS were more likely to list disorders including congenital heart defects, dementia, hypothyroidism, or leukemia. The improved survival was thought to be due to increased placement of infants in homes rather than institutions and to changes in treatment for common causes of death, especially congenital heart disease.

In the same report, malignancies other than leukemia were much less frequent in those with than without DS (standardized mortality odds ratio 0.07) [19]. Possible mechanisms suggested for the low rate of cancer include tumor suppressor genes on chromosome 21, a slower rate of replication or higher rate of apoptosis in DS cells, or less exposure to environmental risks.

Survival in DS is affected by race and sex [19,21]. In the death certificate study noted above, the median age at death was lower among blacks than whites [19]. In contrast to the greater longevity of females in most populations, males with DS appear to have a survival advantage [22,23]. In a series from Western Australia, life expectancy was 58.6 years for the population, and 3.3 years longer for males than females [22].

BASIC SCIENCE RESEARCH AND FUTURE TREATMENT OPTIONS — The development of DS mouse models has provided an opportunity to study emerging pharmacotherapies that target intellectual disabilities common in DS [24-26]. The overexpression of many genes found on the 21st chromosome contributes to learning deficits. Research has focused on hippocampus function related to memory and learning. Areas of interest include specific gamma-aminobutyric acid (GABA) receptor inhibitors, N-methyl-D-aspartic (NMDA) receptor antagonists, and hippocampal dentate gyrus neurogenesis. Preliminary basic science research shows medications such as pentylenetetrazole (PTZ), memantine, and fluoxetine may enhance learning in the DS mouse model. Further studies and clinical trials are needed to show efficacy and safety of these medications in children with DS.

ALTERNATIVE TREATMENTS — Oxidative stress, the imbalance between production and removal of oxygen-derived free radicals, may contribute to some features of DS, such as decreased immune function, premature aging, impaired mental function, and malignancy [27]. In particular, the activity of superoxide dismutase (the gene for which is located on chromosome 21) is increased [28]. Superoxide dismutase is usually regarded as a protective enzyme since it scavenges free superoxide molecules. However, in DS the hydrogen peroxide generated by superoxide dismutase-1 may become toxic in the presence of ferrous iron (Fe2+); it forms the highly toxic hydroxyl radical (OH), which can result in profound cellular damage [29].

Supplementation with antioxidant nutrients has been proposed as potential therapy for DS. Treatments studied include supplementation with zinc, selenium, megavitamins and minerals, vitamin A, vitamin B6, 5-hydroxytryptamine, coenzyme Q10, and targeted nutritional intervention [27,30,31]. These studies have methodologic flaws and provide no convincing evidence that nutritional supplementation improves outcomes in DS. One randomized controlled trial evaluated psychomotor and language development in 156 infants treated for 18 months with daily oral supplementation with one of four programs: antioxidants (selenium, zinc, vitamin A, vitamin E, vitamin C), folinic acid, antioxidants and folinic acid combined, or placebo. This trial found no significant differences between the groups [31].

COUNSELING AND RESOURCES — Counseling may begin when a prenatal diagnosis of DS is made or suspected [1]. The discussion should include the wide range of variability in manifestations and prognosis. Medical and educational treatments and interventions should be discussed. Initial referrals should be made to early intervention, informative publications [32], parent groups, and advocacy groups. In the early teen years, discussion and plans for transition to adulthood should include employment, place of residence, and leisure activities.

Internet resources for parents and patients include the following:

A brochure entitled, "Your baby and Down syndrome: Answers to questions you might have," available in English and Spanish, can be downloaded from the National Down Syndrome Society website.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

SUMMARY

  • Management of Down syndrome (DS) requires an organized approach to ongoing evaluation and monitoring for associated abnormalities and prevention of common disorders. The Committee on Genetics of the American Academy of Pediatrics (AAP) has provided recommendations to assist clinicians in the care of children with DS. These recommendations are available at pediatrics.aappublications.org/content/128/2/393.full.pdf+html.
  • The following evaluations are recommended:

  • Plot growth on standard National Center for Health Statistics or World Health Organization growth charts; monitor for disturbances of growth associated with other disorders, such as hypothyroidism or celiac disease, and for excessive weight gain.
  • Pediatric cardiology evaluation, including an echocardiogram, in the newborn period for congenital heart disease and continued clinical cardiac monitoring in adolescence and adulthood for mitral valve prolapse and aortic regurgitation.
  • Newborn hearing screen and ongoing hearing screening throughout childhood, plus monitoring for otitis media, which is a common cause of hearing loss in children with DS.
  • An ophthalmologic assessment before six months of age and then approximately annually to screen for ophthalmologic disorders.
  • Thyroid function testing in the newborn period with newborn state screens, and repeated at 6 months of age, 12 months of age, and then yearly thereafter.
  • Monitor for symptoms of celiac disease beginning at one year of age. Screening is recommended if signs or symptoms develop.
  • A complete blood count and differential at birth to evaluate for myeloproliferative disorders and polycythemia; ongoing monitoring for signs of leukemia.
  • Check hemoglobin level annually starting at one year of age to screen for iron-deficiency anemia.
  • Neurologic evaluation for signs and symptoms consistent with spinal cord injury at each health supervision visit; symptomatic children should have an MRI to clarify the extent of spinal cord compression.
  • Monitoring for symptoms related to sleep apnea at health supervision visits beginning at age one year; polysomnography is in all children with DS by four years of age.

  • Life expectancy in DS is shorter than that in the general population or in individuals with other causes of intellectual disability. However, survival has improved substantially in the past two to three decades.
  • Internet resources for parents and patients include the following:

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REFERENCES

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  5. Sepúlveda D, Allison DB, Gomez JE, et al. Low spinal and pelvic bone mineral density among individuals with Down syndrome. Am J Ment Retard 1995; 100:109.
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  10. Van Vliet G. How often should we screen children with Down's syndrome for hypothyroidism? Arch Dis Child 2005; 90:557.
  11. McGowan S, Jones J, Brown A, et al. Capillary TSH screening programme for Down's syndrome in Scotland, 1997-2009. Arch Dis Child 2011; 96:1113.
  12. Massey GV, Zipursky A, Chang MN, et al. A prospective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): Children's Oncology Group (COG) study POG-9481. Blood 2006; 107:4606.
  13. Hennequin M, Faulks D, Veyrune JL, Bourdiol P. Significance of oral health in persons with Down syndrome: a literature review. Dev Med Child Neurol 1999; 41:275.
  14. Barr-Agholme M, Dahllöf G, Linder L, Modéer T. Actinobacillus actinomycetemcomitans, Capnocytophaga and Porphyromonas gingivalis in subgingival plaque of adolescents with Down's syndrome. Oral Microbiol Immunol 1992; 7:244.
  15. Kusters MA, Verstegen RH, Gemen EF, de Vries E. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol 2009; 156:189.
  16. Atlantoaxial instability in Down syndrome: subject review. American Academy of Pediatrics Committee on Sports Medicine and Fitness. Pediatrics 1995; 96:151.
  17. Pueschel SM, Herndon JH, Gelch MM, et al. Symptomatic atlantoaxial subluxation in persons with Down syndrome. J Pediatr Orthop 1984; 4:682.
  18. American Academy of Pediatrics. Committee on Genetics. American Academy of Pediatrics: Health supervision for children with Down syndrome. Pediatrics 2001; 107:442.
  19. Yang Q, Rasmussen SA, Friedman JM. Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study. Lancet 2002; 359:1019.
  20. Strauss D, Eyman RK. Mortality of people with mental retardation in California with and without Down syndrome, 1986-1991. Am J Ment Retard 1996; 100:643.
  21. Rasmussen SA, Wong LY, Correa A, et al. Survival in infants with Down syndrome, Metropolitan Atlanta, 1979-1998. J Pediatr 2006; 148:806.
  22. Glasson EJ, Sullivan SG, Hussain R, et al. The changing survival profile of people with Down's syndrome: implications for genetic counselling. Clin Genet 2002; 62:390.
  23. Glasson EJ, Sullivan SG, Hussain R, et al. Comparative survival advantage of males with Down syndrome. Am J Hum Biol 2003; 15:192.
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  27. Ani C, Grantham-McGregor S, Muller D. Nutritional supplementation in Down syndrome: theoretical considerations and current status. Dev Med Child Neurol 2000; 42:207.
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  30. Miles MV, Patterson BJ, Chalfonte-Evans ML, et al. Coenzyme Q10 (ubiquinol-10) supplementation improves oxidative imbalance in children with trisomy 21. Pediatr Neurol 2007; 37:398.
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