1. health and fitness
2. disease

Primar y C are
for Children
and Adolescents
with Down Syndrome
Melissa A. Davidson, MD
KEYWORDS
Down syndrome Primary care health maintenance
Down syndrome, or trisomy 21, is the most common inherited genetic syndrome and
occurs in 1 in 800 to 1000 live births. Improvements in prenatal diagnoses, fetal and
infant surgery, and early intervention programs have allowed patients with Down syndrome to reach their full physical and mental potentials. Therefore, practitioners across
all primary care and subspecialty fields need to be knowledgeable about Down syndrome. The role of the primary care provider in patients with Down syndrome takes
on a broader role than it does for most typical ‘‘well children.’’ With Down syndrome children, as with other children, it is important to document growth, monitor developmental
milestones, provide immunizations, and screen for acute illness. However, for the Down
syndrome patient, more so than for most other patients, the provider must take on the
role of patient advocate. Physicians become a source of support and referral for patients
and families, often acting as a liaison between patients and schools, community-based
services, and subspecialists. Current medical economics, with increased pressures to
see patients quickly despite diminishing fees, make many physicians wary of caring for
the developmentally disabled. Health care guidelines for individuals with Down syndrome1–4 help facilitate quality and efficient care of this growing population of patients.
To enable patients with Down syndrome to attain their highest possible functional status, clinicians need to anticipate health care issues and screen aggressively. This article
reviews the general health care guidelines pertaining to pediatric patients with Down
syndrome and presents, in a systems-based approach, an update of the current evidence behind these guidelines.
PRENATAL SCREENING
Usually, the pediatrician’s first opportunity to interact with the parents of a child with
Down syndrome is after delivery in the hospital or at the first office visit. However,
Lifetime Wellness, Internal Medicine and Pediatrics, 4613 W. Main, Suite A, Kalamazoo,
MI 49006, USA
E-mail address: mdavidson@hcmw.org
Pediatr Clin N Am 55 (2008) 1099–1111
doi:10.1016/j.pcl.2008.07.001
pediatric.theclinics.com
0031-3955/08/$ – see front matter ª 2008 Elsevier Inc. All rights reserved.
1100
Davidson
internal medicine/pediatric physicians or family practice physicians may sometimes
be called upon to counsel families prenatally. In 95% of Down syndrome cases, the
syndrome occurs as a random nondisjunction (trisomy 21). Less commonly, it occurs
as mosaicism (some cells are affected, others are not) or a balanced translocation
(most often involving chromosomes 21 and 14, either parental in origin or spontaneous). Persons with mosaicism may have phenotypic differences. Those with translocation should have parental karyotyping and genetic counseling.
Risk factors for Down syndrome include: advanced maternal age, rising exponentially after the age of 35 years; previous child with Down syndrome or another chromosomal abnormality; parental balanced translocation; and parents with chromosomal
disorders. No evidence has been found identifying hormones, toxins, drugs, vitamin
deficiencies, or viruses as causes of Down syndrome. Prenatal screening can be
offered both first and second trimester, and generally consists of serum and ultrasound testing. The serum triple test consists of maternal alpha fetoprotein, unconjugated estriol, and beta–human chorionic gonadotropin levels. The quadruple test
adds inhibin-A.5 Ultrasound focuses on nuchal lucency and long bone lengths.6
Specific diagnosis is made prenatally through chromosomal analysis from tissue,
either obtained through amniocentesis or chorionic villus sampling. These more invasive screens carry a higher risk of fetal loss. American College of Obstetricians and
Gynecologists guidelines from 2007 recommend ‘‘all women be offered aneuploidy
screening before 20 weeks gestation and all women have the option of invasive testing
regardless of their maternal age.’’7
DOWN SYNDROME PHENOTYPE
Although some physicians are hesitant to share their suspicions of Down syndrome
with new parents following delivery, it is imperative to make a diagnosis as soon as
possible. This allows screening for life-threatening complications of Down syndrome
before discharge after birth. At delivery, the most striking features of Down syndrome
are hypotonia, lymphedema, nuchal cord thickening, microcephaly, epicanthal folds,
and simian creases. Other phenotypic features of Down syndrome include midface
hypoplasia, clinodactyly (curved digits), and brachydactyly (shortened digits). Some
degree of mental impairment is universal, and declares itself over time.8,9 Figs. 1
and 2 depict some of these common features in an older child. Remember, not all
patients have all of these phenotypical features; variable expression of phenotype is
what defines a ‘‘syndrome.’’ Also, while a clinician is busy tallying up the phenotypic
features supporting the diagnosis of Down syndrome, family members are more apt
to see ‘‘mother’s eyes’’ and ‘‘grandpa’s forehead.’’ For this reason, clinical diagnoses
should be followed as soon as possible by genetic testing (chromosomal karyotyping)
and counseling as appropriate. Over time, phenotypic features may coarsen and
become more apparent. This may be related to premature aging, which is associated
with trisomy 21. Short stature is characteristic of Down syndrome, and may be exacerbated by comorbid conditions, such as hypothyroidism and cardiac disease.
It is a myth that all patients with Down syndrome have severe mental retardation, as
many children and adults with Down syndrome are functioning independently with
mild to moderate mental impairment. It is also a myth that fewer phenotypic features
represents ‘‘milder disease,’’ as mental impairment is not correlated with physical features. It is true, unfortunately, that society reacts negatively to those who look ‘‘most
different’’; this is the rationale used by those advocating cosmetic plastic surgery in
Down syndrome (a very controversial topic).
Children and Adolescents with Down Syndrome
Fig. 1. Phenotypical features of Down syndrome in a 9-year-old boy. Note the epicanthal
folds, midface hypoplasia, microcephaly, strabismus, and irregularly spaced dentition.
GROWTH AND DEVELOPMENT
Compared with newborns without Down syndrome, newborns with Down syndrome
tend have lower birth weights, shorter lengths, and smaller head circumferences.10,11
During infancy and early childhood, this trend continues, confounded by the hypotonia
and early feeding problems characteristic of Down syndrome babies. Mothers may
require additional lactation support for successful nursing. Down syndrome is associated with a decreased resting metabolic rate and short stature. As a result, weight
Fig. 2. Simian crease.
1101
1102
Davidson
increases disproportionately to height in children with Down syndrome, such that most
4-year-olds are already obese compared with ‘‘typical’’ children.12 Early physical
therapy and occupational therapy focusing on healthy eating and mobilization are
important tools to counter this tendency. In monitoring growth, it is important for the
provider to use both Down syndrome–specific growth curves and standard curves.
This allows tracking of individual curves. A plateau or decrease in growth could represent a secondary condition, such as hypothyroidism.
Management of obesity in Down syndrome is similar to that in others: increase
activity and decrease caloric intake, with emphasis on high-quality foods. As children
grow up, friends and social support become critical to their success in weight management. Limiting calories to manage weight may result in deficiencies of micronutrients. Recommendation of a daily multivitamin and calcium supplement may be
appropriate for older children.
Developmental milestones tend to follow the same order, but occur at variable
rates, depending on the child’s severity of mental retardation and comorbid medical
conditions. Delays are almost always evident within the first year of life and, in general,
the average age of sitting, crawling, and walking is about twice the typical age.13 This
can create anxiety in parents, but it is important to encourage ongoing stimulation and
monitor for consistent gain in milestones.
CARDIAC MANIFESTATIONS OF DOWN SYNDROME
Patients with Down syndrome have a much higher incidence of congenital heart disease, and also a higher risk of acquired valvular heart disease. A frequently referenced
population-based study found 44% of infants born with Down syndrome to have some
form of congenital heart disease.14 Endocardial cushion defects (atrioventricular
septal defects) are the most common heart lesion seen (45%), with ventricular septal
defects also seen commonly (35%). Prenatal ultrasounds pick up many of these
lesions. Most defects have been described in Down syndrome, but isolated secundum
atrial septal defects (8%), isolated persistent patent ductus arteriosis (7%), and
isolated tetralogy of Fallot (4%) are the most frequently seen ‘‘other lesions.’’ At birth,
or at the time Down syndrome is diagnosed, the infant should have an echocardiogram and, if available, consultation with a pediatric cardiologist. This is important
even in the absence of a clinical heart murmur because serious heart disease can
be masked by the increased pulmonary vascular resistance.1,2,15 Repair of cyanotic
lesions should occur as soon as appropriate medically.
It remains an important job for the primary care provider to manage antibiotic
prophylaxis for subacute bacterial endocarditis. This job requires knowledge of the
American Heart Association’s revised guidelines,16 which stress the need to limit
the use of use of antibiotics. Clinicians should be careful not to overmedicate patients
who have lesions that no longer require antibiotic prophylaxis. The following conditions mandate continued use of antibiotic prophylaxis: prosthetic cardiac valves; prior
endocarditis; unrepaired cyanotic congenital heart defects, including palliative shunts
and conduits; completely repaired congenital heart defect with prosthetic material or
device within 6 months of the procedure or with residual defect at or near the site of
prosthesis; and cardiac transplant recipients with valvular dysfunction. For all patients,
best practices for dental hygiene remain the mainstay of endocarditis prevention.
Even those without congenital heart defects require ongoing surveillance for development of heart disease. The rate of acquired mitral valve prolapse is nearly 50%, and
for aortic insufficiency greater than 15%.17,18 Careful cardiac examination, with dynamic auscultation is recommended yearly. If there are symptoms or examination
Children and Adolescents with Down Syndrome
findings of acquired valvular disease, repeat echocardiogram and cardiac consultation should be sought immediately. There are not sufficient data to warrant interval
studies in asymptomatic patients.
GASTROINTESTINAL PROBLEMS ASSOCIATED WITH DOWN SYNDROME
Although much less common than cardiac defects, anomalies of the gastrointestinal
tract are the other potentially life-threatening defects that should be looked for immediately after making the diagnosis of Down syndrome. Five percent of infants born with
Down syndrome have an anomaly of the gastrointestinal tract. In descending order of
frequency, these comprise duodenal stenosis or atresia, annular pancreas, imporforate anus, and esophageal atresia with tracheoesophageal fistula.19 A careful history
and physical examination, keeping a high clinical index of suspicion, is typically all that
is needed to screen for gastrointestinal anomalies. The clinical picture should guide
imaging and endoscopic studies. The ‘‘double-bubble sign’’ on radiograph is the
hallmark of duodenal atresia. Hirschprung’s disease also occurs more commonly in
Down syndrome than in the general population. Problems identified should prompt
consultation with a pediatric surgeon.
Decreased gut motility and feeding issues contribute to the chronic constipation
problems that many patients with Down syndrome battle. Occupational therapists
can assist with feeding strategies to improve the intake of fluids and fiber, strategies
to improve levels of physical activity, and even intestinal massage. Fiber supplements
and safer laxatives, such as polyethylene glycol, can also be used to treat chronic constipation. The presence of severe constipation should be a wake-up call to screen
appropriately for thyroid disease and celiac disease.
Celiac disease (also known as gluten enteropathy and nontropical sprue) is an
autoimmune disorder in which exposure to gluten (the protein in wheat, barley,
and rye) produces a variety of gastrointestinal symptoms. It has a much higher
prevalence in the Down syndrome population (5%–15%) compared with the general
population. Classic symptoms are those of intestinal malabsorption (diarrhea, steatorrhea, anemia, nutritional/ vitamin deficiency, and weight loss). Villous atrophy is
the hallmark histologic finding on duodenal and jejunal biopsies. The symptoms
and mucosal changes resolve with strict adherence to a gluten-free diet.20–23
More commonly, though, celiac disease is silent or latent. It can present at any
age and more often with vague symptoms, such as constipation, dyspepsia, poorly
localized abdominal pain, and flatulence. Celiac disease is likely also underdiagnosed in the general population, but the delay to diagnosis is significantly longer
in Down syndrome where the nonspecific symptoms are too often just attributed
to the underlying syndrome.
There appears to a genetic predisposition for celiac disease as well, with an association with HLA DQ2. Several screening tests are available, although there is not
a consensus as to the best screening test (IgA antiendomysial antibody has been
considered the gold standard, but anti–tissue transglutamidase is becoming more
widely used). Currently, the Down Syndrome Medical Interest Group (United States)
recommends initial screening at 2 years of age with IgA tissue transglutaminase
and total IgA. Symptomatic children less than 2 years of age should have IgA antigliadin antibody in addition to IgA tissue transglutaminase and total IgA. The costeffectiveness of serial screening for celiac disease is still not validated.23 Similarly,
the role of HLA testing remains unclear. Therefore, a high clinical index of suspicion
for celiac disease should be maintained at both well and sick visits, with testing as
clinically indicated.
1103
1104
Davidson
PULMONARY PROBLEMS IN DOWN SYNDROME
The pulmonary problems of Down syndrome have both surgical and medical implications. Pathologic studies have documented pulmonary hypoplasia, with equal severity
in the presence or absence of associated cardiac defects. Researchers have found
evidence of both decreased numbers of alveoli and decreased surface area, likely
contributing to the propensity of pulmonary hypertension seen in Down syndrome.24
These anatomic differences, in combination with immunodeficiencies, make patients with Down syndrome more susceptible to pulmonary infections. There is a higher
rate of both cystic and interstitial disease, with chronic silent aspiration aggravating
the latter. No adequately controlled studies have shown that pulmonary hypoplasia
causes high-altitude pulmonary edema or contributes to attention deficit disorder,
but these have both been postulated.
Screening for a pulmonary problem is best directed by the history and clinical examination. Routine chest radiographs are not indicated. Behavioral modification to minimize aspiration, such as taking small bites and careful chewing, or working with
occupational and speech therapists are recommended. Preventive strategies to
reduce infections and early management of infections are both important. For those
severely ill or requiring general anesthesia, pulmonary hypoplasia may present increased challenges in ventilation and extubation.
EAR, NOSE, AND THROAT PROBLEMS IN DOWN SYNDROME
The midface hypoplasia and ear anomalies associated with Down syndrome present
both challenges for the clinician and medical problems for the patient. As pediatricians, we pride ourselves on our otoscopy skills. The Down syndrome ear, however,
is often small and posteriorly positioned. The canals are quite narrow, and standard
equipment is frequently not sufficient for visualization of the tympanic membranes.
Conductive hearing loss due to thick secretions and undiagnosed ear infections is
common. Refer to an ear, nose, and throat specialist early if problems are suspected
or an optimal examination cannot be done in the ambulatory setting. Sensorineural
hearing loss is also higher than in the general population and the risk of loss increases
with age.25 Current recommendations are to screen at birth, most often this is done
with brainstem audio-evoked responses. Serial screening should be done annually;
clinical examination and pure tone audiometry may be sufficient, but brainstem audio-evoked response testing with an audiologist every 2 years is optimal.1,2
Chronic sinus and nasal problems result from small airways. Similarly, tracheomalacea and obstructive sleep apnea are more common. Untreated, apnea contributes to
pulmonary hypertension and congestive heart failure.
OPHTHALMOLOGY AND DOWN SYNDROME
Epicanthal folds and Brushfield spots are a bigger dilemma for physicians on medical
examinations than in the clinical setting, as they are benign and do not interfere with
vision. Although they occur in the general population, they are so much more common
in Down syndrome patients that they’ve become pathognomic for the syndrome.
Brushfield spots appear as a speckled pattern, circumlinear on the iris, and actually
comprise an aggregation of normal iris connective tissue.26 Of greater significance
are the higher prevalence of congenital and acquired cataracts; strabismus; nystagmus; and refractory errors. Midface hypoplasia and microcephaly often present
everyday challenges in fitting glasses. Older children and adolescents develop keratoconus, a noninflammatory thinning of the cornea, which causes coning and visual
Children and Adolescents with Down Syndrome
distortion as well as light sensitivity. Blepharitis and conjunctivitis are also frequent eye
problems that might present to the primary care clinic. The current recommendation is
to have an ophthalmologic examination every 1 to 2 years, and to refer sooner for
symptoms that can’t be easily managed in the office.1,2
ENDOCRINOLOGY ISSUES IN DOWN SYNDROME
Thyroid disease takes on many faces in Down syndrome, and longitudinal studies
have found up to 30% of Down syndrome patients have thyroid function abnormality.
Clearly, there is a higher rate of autoimmune hypothyroidism (Hashimoto).27 Rates of
congenital hypothyroidism are also increased, although more concerning is that the
clinical examination is unreliable in view of the syndrome-associated lymphedema,
hypotonia, and growth issues previously discussed. While much higher rates of positive newborn screens are seen in Down babies compared with the general population,
there is also a concern that certain thyroid disorders are not being detected in these
standardized newborn screens.23 For this reason, repeat testing is recommended at
6 months of age. Thereafter, it is recommended to repeat thyroid testing annually,
using thyrotropin and free thyroxine. There is no clear role for thyroid antibody testing.
Meanwhile, the task of clinically managing subclinical or compensated hypothyroidism is controversial.
Hyperthyroidism is less common than hypothyroidism in Down syndrome patients.
Even so, hyperthyroidism occurs more commonly in Down syndrome patients than in
the general population. Hyperthyroidism is also most often immune mediated. Another
curiosity is the observation that Down syndrome patients with thyroid disease have
a threefold increase of hepatitis B carrier state.28 This is likely related to cellular immunity abnormalities, but adds weight to the importance of keeping this group of patients
up to date on their hepatitis B immunizations.
Children who have Down syndrome have an increased risk of diabetes mellitus. In
children who have Down syndrome, type 1 diabetes mellitus is associated with autoimmune factors, and type 2 diabetes mellitus is associated with obesity and premature
aging.29 Screening should be based on clinical suspicion and treatment should
include diet modifications, exercise, hypoglycemic medication, and referral to an
endocrinologist as indicated.
Growth hormone abnormalities have been postulated, but the clinical significance
remains undetermined due to lack of quality studies. The Down’s Syndrome Medical
Interest Group recommends against the routine use of growth hormone injections.2
IMMUNOLOGIC MANIFESTATIONS OF DOWN SYNDROME
Immune dysfunction has been attributed as the cause of increased infections, cancers, and autoimmune diseases in patients with Down syndrome. The mechanism
of dysfunction is likely multifactoral, including derangements in chemotaxis, and deficiencies in cellular immunity and IgG subclasses. Cellular immunity problems are likely
responsible for the prevalence of gingivitis and periodontal disease in older children
and adolescents. Although total IgG may be normal, there are typically IgG subclass
deficiencies (classes 2 and 4) that are responsible for the recurrent sinopulmonary infections and occasionally the more serious systemic infections seen.30,31 It has been
postulated that selenium deficiency may be associated with some of the immune
problems seen in Down syndrome, but there is not a recommendation for general supplementation. Clearly, it is important to immunize children and adolescents with Down
syndrome as you would other children. The standard guidelines are ever changing,
and should be reviewed annually. In addition, Down syndrome patients should be
1105
1106
Davidson
considered candidates for serial boosters of pneumovax. Outside of the group or institution setting, tuberculosis screening for asymptomatic patients should be based on
social and geographic risk factors.
HEMATOLOGIC DISORDERS IN DOWN SYNDROME
Both the red and white cell lines appear impacted by Down syndrome. Polycythemia is
seen in as many as 60% to 65% of newborns, although it is not usually clinically significant. Several types of leukemia are seen in Down syndrome. Most unique is transient myeloproliferative disorder of the newborn, which is described in up to 20% of
Down syndrome newborns. Typically, patients are asymptomatic and, unlike other
leukemias, hemoglobin and neutrophil counts often remain in the normal range. It is
characterized by high blast counts, often disproportionately high in the peripheral
blood compared with the marrow. There may be an associated vesiculopustular
rash while the blasts are present. Typically, the blasts disappear by 3 months of
age.32,33 Blast infiltration can occasionally cause more serious complications and
antenatal cases can be associated with hydrops fetalis and fetal loss. A significant
number of these patients who recover from transient myeloproliferative disorder later
develop acute megakaryoblastic leukemia, subtype M7. An X-chromosome gene
mutation responsible for GATA-1 (a transcription factor responsible for megakaryocyte differentiation) seems to be involved.33,34
The rate of acute lymphocytic leukemia is also high in Down syndrome. Characteristics of the disease are more consistent with non-Down patients, as is outcome data
following standard chemotherapy.17,35 Lymphomas are increased relative to the general population, but the risk of most solid tumors is decreased. An important exception
is the high risk of testicular germ cell tumors, up to 50 times the rate of the general
population. Seminomas are the most common type, with a mean age of diagnosis
around 30. Males with Down syndrome as a rule have hypogonadism, and cryptorchidism is also common. Testicular examination should begin in childhood and continue
annually into adulthood. Orchipexy should be considered to facilitate the testicular
examination and early detection of tumor.36,37
ORTHOPEDIC PROBLEMS IN DOWN SYNDROME
A number of musculoskeletal problems occur with higher frequency in Down syndrome
and may require intervention from physical therapists, occupational therapists, or
orthopedic surgeons. Congenital problems, such as developmental dysplasia of the
hip and acetabular dysplasia, may occur. Older children and adolescents who develop
a limp should be worked up for acquired hip dislocation, a risk related to the ligamentous laxity they typically have. This laxity also contributes to chronic patellar dislocation,
pes planus, and ankle pronation (Figs. 3 and 4). Obesity, hypotonia, and premature
aging may be reasons for higher rates of scoliosis and degenerative joint disease.
The most controversial screening in Down syndrome remains the recommendation
for cervical spine films for atlantoaxial instability (AAI). Nearly 15% of patients with
Down syndrome have laxity of the first and second cervical joint, which is considered
to be joint instability if the space between the two vertebrae exceeds 4.5 mm on lateral
neck films taken in flexed, neutral, and extended positions by a competent radiology
technician. Presence of AAI does not correlate well with symptoms (far fewer patients
have symptoms than have radiologic diagnosis of AAI), nor does participation in sports
often trigger spinal cord compromise. Theoretically, however, sports that place
athletes at highest risk for neck compression, such as boxing, diving, horseback
riding, gymnastics, and jumping on the trampoline, could cause spinal cord injury.
Children and Adolescents with Down Syndrome
Fig. 3. Ankle pronation, loss of arch due to ligamentous laxity and pes planus.
The American Academy of Pediatrics Committee on Sports Medicine revised its policy
statement in 1995, but did not clarify the issue much with their recommendation that
lateral neck radiographs in flexion, extension, and neutral positions are of ‘‘potential,
but unproven value in detecting patients at risk of spinal cord injury during sports participation.’’38 At that time, recommendations were made for screening at age 3, 12,
and 18 years. Dr. Cohen23 revisited this topic more recently (2006), but found that
there is still discrepancy between major guidelines and discordance between radiograph findings, symptoms, and risk of spinal cord catastrophe. Signs and symptoms
of spinal cord injury include neck pain, decreased range of motion of the neck, gait disturbance, bowel or bladder dysfunction or incontinence, hyperreflexia, and paresthesias. Rarely, it can cause hemiparesis, plegias, and even death. Patients, parents, and
coaches should be educated that the presence of any of these symptoms should
prompt an immediate medical evaluation. Neuroimaging (MRI) and neurosurgical consultation would be indicated. Dr. Cohen concluded that, in the absence of definitive
Fig. 4. Pes planus.
1107
1108
Davidson
data, standard recommendations for lateral cervical spine films in flexion, neutral, and
extension should be continued at age 3 to 5 years. Obtaining neural cord width measurement may increase the yield of these studies and better identify those who need to
have MRI and neurosurgical consultation. Subspecialists and anesthesiologists who
perform procedures that require neck flexion or hyperextension should use universal
spine precautions, as negative screening radiographs do not eliminate the risk of
spinal cord compromise. There is limited data on the benefits of serial radiographs,
but for the time being, Special Olympics continues to require them for high-risk sports.
NEURODEVELOPMENT AND PSYCHIATRIC ISSUES IN DOWN SYNDROME
As previously mentioned, mental retardation to some degree is universal in Down
syndrome. Most typical is mild to moderate retardation, but individuals have been
documented from profound retardation to normal IQ.39 Since social IQ often exceeds
their overall IQ, persons with Down syndrome may function at a higher level than persons with mental retardation of other causes at the same IQ level.
Seizures in Down syndrome patients tend to have a bimodal distribution, occurring
most commonly in infancy and then later again after puberty. Early on, infantile spasms
predominate. Later on, tonic-clonic seizures predominate. Seizures in Down syndrome patients should be treated in a way similar to those of the general population.
Dual diagnoses create challenges for both families and clinicians. Autism, anxiety
disorders, depression, and attention deficit/hyperactivity disorder have all been described in Down syndrome patients. Self-talk is very common in Down syndrome adolescents and young adults and is often overdiagnosed as frank psychosis. Identifying
mental health providers specializing, or comfortable with, developmental delay is
critical to management of these dual diagnoses. Tertiary centers with Down syndrome
clinics could be helpful in testing, diagnosing, and recommending treatment in these
challenging situations.
Dementia, Alzheimer’s type, is clearly associated with Down syndrome. The hallmark histologic feature of Alzheimer’s disease is amyloid plaque on brain biopsy.
Chromosome 21 carries the amyloid precursor protein gene, which is purported to
be overexpressed in trisomy 21. Advances in gene sequencing have helped delineate
several specific genes on chromosome 21 related to mitochondrial energy generation.
Mitochondrial dysfunction is believed a critical link in the development of Alzheimer’s
disease in Down syndrome.17
PUBERTY AND THEN SOME
Transition care issues are numerous, as more patients than ever are entering adolescence and adulthood. Personal communication with a number of patients facing these
transitions is that they are seeking a provider who will listen to them and allow them to
be actively involved in their health care decisions. They need your help in gaining independence. It is an important role of the primary care provider to help families
seek sound advice regarding estate planning, application for medical disability, independent living facilities, and transition care plans as they graduate out of school-based
support systems. Many communities have advocacy programs for the developmentally disabled that can assist in referrals to these resources. Keeping patients involved
in sports, dances, and work opportunities is important for both managing obesity and
avoiding depression. Change is particularly stressful for the mentally impaired, so
clinicians should help them anticipate change and should work with them by roleplaying transitions. Inquire about the health of family members and care-providers.
Children and Adolescents with Down Syndrome
The timing and progression of puberty tends to be predictable. Females typically
have normal genitalia and are capable of becoming pregnant. It is important that counseling be done regarding sexuality, pregnancy, and responsible dating. The developmentally disabled in general are at high risk for abuse, so self-advocacy skills should
be taught and either supervised environments or the ‘‘buddy system’’ must be encouraged. Menstrual hygiene and premenstrual syndrome can be problematic. Behavior
problems are often noted to be cyclically related. Hormonal therapies should be considered, as they would for patients with similar problems in the general population.
Sterilization in the mentally impaired patient is an ethically charged topic, and should
be evaluated carefully on an individual case basis with patient, family, and surgeon.
Like the general population, pelvic examinations and Pap smears should be offered
within 3 years of becoming sexually active, or at least the pelvic examination considered by age 21 (earlier for menstrual problems). Often, extra time and reassurance can
allow the pelvic examination to occur in the office. Sometimes, a speculum examination is not tolerated and either a ‘‘blind swab’’ inserted over an examiners single digit or
a pelvic ultrasound have to suffice. Individual risk versus benefit should be assessed
before doing an examination under general anesthesia.
Males most often have hypogonadism. Undescended testes are not uncommon
and, as mentioned earlier, should be brought down surgically to aid in the testicular
examination and identification of germ cell tumors. Males are almost always infertile.
MISCELLANEOUS ISSUES IN DOWN SYNDROME
Dermatology problems abound in children and adolescents with Down syndrome. Dry
skin, atopic dermatitis, and icthyosis are frequent and should be treated with the
appropriate topical therapies. Proper hygiene is critical for preventing folliculitis and
more serious bacterial or fungal infections. Norwegian scabies and autoimmune
conditions of the skin, including alopecia and vitiligo, occur more frequently than
the general population.
Dental problems are also diverse in this population. Teeth erupt unpredictably, palates are often high arched, and cellular immunity issues contribute to later periodontal
disease. Dental referrals should happen by 2 years and should be ongoing every
6 months. Orthodontia should be as tolerated, depending on the situation.
Alternative therapies have been proposed but are not recommended by the Down’s
Syndrome Medical Interest Group because of the lack of data to substantiate them
and, in some cases, the potential for unnecessary suffering and side effects (piracetam, sicca cell therapy, chiropractic manipulation, and plastic surgery). Nutritional
and vitamin therapies similarly lack controlled studies to prove their efficacy. Until
additional evidence of benefit is available, these therapies should not be endorsed.2
SUMMARY
Patients with Down syndrome are likely to be encountered in every type of medical
practice. It is important to have an understanding of the medical problems associated
with Down syndrome. While studies are ongoing regarding some of the best practices
in diagnosing and managing Down syndrome and comorbid illnesses, comprehensive
guidelines from the Down Syndrome Medical Interest Group and the American Academy of Pediatrics make it easier to care for children and adolescents with Down Syndrome. To ensure the best possible long-term outcome for these patients, clinicians
should provide routine well-child examinations and immunizations while maintaining
a high index of suspicion for comorbid conditions more common in Down syndrome.
The primary care provider should be prepared to provide information on community
1109
1110
Davidson
resources, coordinate care with subspecialists, and refer to early intervention services
as soon as the diagnosis is made.
REFERENCES
1. American Academy of Pediatrics. Health supervision for children with Down
syndrome, Committee on Genetics. Pediatrics 2001;107:442–9.
2. Cohen WI, for the DSMIG. Healthcare guidelines for individuals with Down
syndrome. Reprinted from Down Syndrome Quarterly 1999;4:1–29.
3. Cohen WI, for the DSMIG. Healthcare guidelines for individuals with Down syndrome. Down syndrome preventative medicine checklist. Reprinted from Down
Syndrome Quarterly 1996;1:1–18.
4. Healthcare guidelines for individuals with Down syndrome. Available at: www.
downsyn.com/guidelines. Accessed in 1996.
5. ACOG practice bulletin no. 77: screening for fetal chromosomal abnormalities.
Obstet Gynecol 2007;109:217–28.
6. Malone FD, Canick JA, Ball RH, et al. First-trimester or second-trimester, or both,
for Down’s syndrome. N Engl J Med 2005;353:2001–11.
7. Nicholaides KH. Nuchal translucency and other first-trimester sonographic
markers of chromosomal abnormalities. Am J Obstet Gynecol 2004;191:45–67.
8. Jones KL. Down syndrome. In: Smith’s recognizable patterns of human malformation. 6th edition. Philadelphia: Elsevier Saunders; 2006. p. 7.
9. Epstein CJ. Down syndrome (trisomy 21). In: Scriver CR, Beaudet AL, Sly WS,
editors. The metabolic and molecular bases of inherited disease. 8th edition.
New York: McGraw-Hill; 2001. p. 1223.
10. Toledo C, Alembik Y, Aguirre Jaime A, et al. Growth curves of children with Down
syndrome. Ann Genet 1999;42:81–9.
11. Myrelid A, Gustafsson J, Ollars B, et al. Growth charts for Down’s syndrome from
birth to 18 years of age. Arch Dis Child 2002;87:97–103.
12. Rubin SS, Rimmer JH, Chicoine B. Overweight prevalence in persons with Down
syndrome. Ment Retard 1998;36:175–81.
13. Winders PC. Gross motor milestone statistics. In: Gross motor skills in children
with Down syndrome: a guide for parents and professionals. Baltimore (MD):
Woodbine House; 1997. p. 228.
14. Freeman SB, Taft LF, Dooley KJ, et al. Population-based study of congenital heart
defects in Down syndrome. Am J Med Genet 1998;80:213–7.
15. Roizen NJ. Medical care and monitoring for the adolescent with Down syndrome.
Adolesc Med State Art Rev 2002;13:345–58.
16. Wilson W, Taubert KA, Gewitz M, et al. Prevention of endocarditis: guidelines from
the American Heart Association. Circulation 2007;116(5):1736–54.
17. Roizen NJ, Patterson D. Down’s syndrome. Lancet 2003;361:1281–9.
18. Geggel RL, Obrien JE, Feingold M. Development of valve dysfunction in adolescents and young adults with Down syndrome and no known congenital heart disease. J Pediatr 1993;122:821–3.
19. Pameijer CR, Hubbard AM, Coleman B, et al. Combined pure esophageal
atresia, duodenal atresia, biliary atresia, and pancreatic ductal atresia: prenatal diagnostic features and review of the literature. J Pediatr Surg 2000;35:
745–7.
20. Nisihara NM, Kotze LM, Utiyama SR, et al. Celiac disease in children and adolescents with Down syndrome. Jornal de Pediatria 2005;81:373–6.
Children and Adolescents with Down Syndrome
21. Carlsson A, Axelsson I, Boruls S, et al. Prevalence of IgA-antigliadin antibodies
and IgA- antiendomysium antibodies related to celiac disease in children with
Down syndrome. Pediatrics 1998;101:272–5.
22. Gale L, Wimalaratna H, Brotodiharjo A, et al. Down’s syndrome is strongly associated with celiac disease. Gut 1997;40:492–6.
23. Cohen WI. Current dilemmas in Down syndrome clinical care: celiac disease, thyroid disorders and atlanto-axial instability. Am J Med Genet C Semin Med Genet
2006;142C:141–8.
24. Cooney TP. Pulmonary hypoplasia in Down’s syndrome. N Engl J Med 1982;307:
1170–3.
25. Roizen NJ, Wolters C, Nicol T, et al. Hearing loss in children with Down syndrome.
J Pediatr 1993;123:S9.
26. Webster’s New World: Medical Dictionary, 2nd edition, 2003.
27. Tuysuz B, Beker DB. Thyroid dysfunction in children with Down’s syndrome. Acta
Paediatr 2001;90:1389–93.
28. May P, Kawanishi H. Chronic hepatitis B infection and autoimmune thyroiditis in
Down syndrome. J Clin Gastroenterol 1996;23(3):181–4.
29. VanGoor JC, Massa GG, Hirasing R. Increased incidence and prevalence of
diabetes mellitus in Down’s syndrome. Arch Dis Child 1997;77:186.
30. Ugazio AG, Maccario R, Notarangelo LD, et al. Immunology of Down syndrome:
a review. Am J Med Genet Suppl 1990;7:204–17.
31. Nespoli L, Burgio GR, Ugazio AG, et al. Immunologic features of Down syndrome:
a review. J Intellect Disabil Res 1993;37:543–51.
32. Zipursky A. Transient leukaemia—a benign form of leukaemia in newborn infants
with trisomy 21. Br J Haematol 2003;120:930–8.
33. Webb D, Roberts I, Paresh V. Haematology of Down syndrome: review. Arch Dis
Child Fetal Neonatal Ed 2007;92:F503–7.
34. Taub JW, Mindschau G, Ge Y, et al. Prenatal origin of GATA-1 mutations may be
an initiating step in the development of megakaryocytic leukemia in Down syndrome. Blood 2004;104:1588–91.
35. Lange B. The management of neoplastic disorders of haematopoiesis in children
with Down syndrome. Br J Haematol 2000;110:512–24.
36. Roberge D, Souhami L, Laplante M. Testicular seminoma and Down’s syndrome.
Can J Urol 2001;8:1203–6.
37. Galley R. Medical management of the adult patient with Down syndrome. JAAPA
2005;18:45–52.
38. Atlanto-axial instability: 1995 American Academy of Pediatrics Committee on
Sports Medicine revised position statement. Pediatrics 1996;96:151–4.
39. Saenz RB. Primary care of infants and young children with Down syndrome.
Am Fam Physician 1999;59:381–95.
1111