Primary Care of Children and Adolescents with Down
Syndrome: An Update
Rebecca A. Baum, MD,a Patricia L. Nash, MD,a Jessica E.A. Foster, MD,a
Michelle Spader, Psy D,b Karen Ratliff-Schaub, MD,a and Daniel L. Coury, MDa
Introduction
Historical Perspective
own syndrome is perhaps the most recogniz-
D able and well-described genetic syndrome en-
countered in pediatrics. Undoubtedly seen in
ages past, John Langdon Down was the first to
describe it in great detail in his landmark paper titled
Observations on an Ethnic Classification of Idiots in
1866. He believed that a certain group of people with
mental retardation had physical features similar to that
of the Asian or Mongolian races. The terms Mongo-
lian or Mongoloid became widely used to describe
these individuals. It was not until the 1970s that this
term became pejorative and fell into disuse. It was
replaced by the eponym, Down syndrome. In the 19th
and early 20th centuries, there were a variety of
theories regarding the cause of Down syndrome in-
cluding maternal tuberculosis or hypothyroidism. In
1959, Lejeune and coworkers confirmed the presence
of trisomy 21 as the cause of Down syndrome.1
In the early part of the 20th century, parents were
given a very bleak outlook for their infant with Down
syndrome. They were often told that the child would
not live long, or that he or she would never walk, talk,
or even recognize their own parents. Parents were also
advised to place their child in an institution and the
parents should tell everyone that the baby had died.
Fortunately, attitudes began to change, both socially
From the aOhio State University, College of Medicine, Section of
Developmental/Behavioral Pediatrics, Nationwide Childrens Hospi-
tal, Columbus, Ohio; and bThe Ohio State University, College of
Medicine, Section of Psychology, Nationwide Childrens Hospital,
Columbus, Ohio.
Curr Probl Pediatr Adolesc Health Care 2008;38:241-261
1538-5442/$ - see front matter
2008 Mosby, Inc. All rights reserved.
doi:10.1016/j.cppeds.2008.07.001
Curr Probl Pediatr Adolesc Health Care, September 2008
and medically, by the 1960s. Many families chose not
to place their children in institutions and found that
they became unique and valued members of the
family. Medical attitudes evolved further by the 1970s
and 1980s. Infants born with Down syndrome were
offered the same medical care and interventions that
typical children received. They underwent cardiac
surgery to correct congenital heart defects, which
greatly increased their longevity. They also received
other medical interventions that reduced morbidity and
mortality.
Early in the 21st century we have a much better
understanding of what these individuals can accom-
plish in a nurturing environment. Institutions for chil-
dren with mental retardation have become a thing of
the past. The overwhelming majority of these children
are raised within their biological families. Their edu-
cational rights are protected under the Individuals with
Disabilities Act of 1991, which requires that all states
provide a full appropriate public education for all
children with disabilities. Atypical children can thrive
when they are integrated with typically developing
children, a now common practice from early interven-
tion programs through secondary school. Many of
these individuals grow up to live semi-independently,
in group homes or other assisted-living arrangements.
Many of them work in their local communities or in
sheltered workshops. Some even learn to drive and get
married. Characters with Down syndrome have been
featured prominently in television shows, major mo-
tion pictures, and best-selling novels in recent years.
As our cultural acceptance of these unique individuals
evolves, we become more aware of their capabilities,
rather than solely focusing on their disabilities.
The purpose of this article is to provide a practical
and up-to-date review of children and adolescents with
Down syndrome for the primary care clinician. Key
points include a review of common physical and
241
mental characteristics of those with Down syndrome, a
discussion of medical recommendations for the provi-
sion of comprehensive primary care, and consideration
of the impact of Down syndrome on the individual and
their family.
Etiology
Down syndrome is the most common chromosomal
abnormality among live births and the most common
cause of Intellectual Disability.2 In 2006, the Center
for Disease Control estimated the rate as 1 per 733 live
births in the United States (5429 new cases per year).3
Down syndrome, or trisomy 21, occurs when genetic
material from chromosome 21 is present in three
copies instead of two. This can result from two
different mechanisms: nondisjunction and transloca-
tion. Individuals may contain the extra copy in all
cells, or it may be present in only a portion of cells,
which is termed mosaicism.
The most common cause of Down syndrome is
nondisjunction, the cause in 95% of cases.4 In this
scenario, an extra copy of chromosome 21 is present in
all cells, resulting in a total of 47 chromosomes and
three separate copies of chromosome 21. Nondisjunc-
tion results from an error in the segregation of chro-
mosomes during meiosis, which causes the formation
of a gamete that contains two copies of chromosome
21. When fertilization occurs, a normal gamete (which
contains one copy of chromosome 21) and the altered
gamete combine to form a zygote with three copies of
chromosome 21. In most cases the extra chromosome
is of maternal origin.5
Another possible but less common mechanism oc-
curs when genetic material from chromosome 21
becomes attached to another chromosome. This is
termed a translocation. In this case, 46 chromosomes
are present with one chromosome having extra mate-
rial from chromosome 21 attached. A translocation
can occur as a result of a new mutation, or it can be
inherited from a parent. Most cases of translocation
are de novo (around three-quarter of cases), with the
remaining cases being a balanced translocation inher-
ited from a phenotypically normal parent.6 The exact
percentage of de novo versus inherited translocations
varies based on the specific chromosomes involved in
the translocation.
Down syndrome also can result from the process of
mosaicism. Mosaicism refers to nondisjunction that
occurs after creation of the zygote. This creates two
different cell lines, one with three copies of chromo-
242
some 21 and one with two copies. It is important to
remember that the percentage of cells with mosaicism
in the peripheral blood may not correspond to the
percentage of cells with mosaicism in other parts of
the body, such as the brain or the heart. The phenotype
seen in individuals with mosaicism is dependent on the
number and type of cell lines affected. Individuals
with mosaicism may have features that are more
subtle, or they may show the full array of phenotypic
features seen in individuals with trisomy 21.7 Mosa-
icism is thought to be responsible for less than 1% of
Down syndrome cases, with the remaining 4% of
cases due to translocation.4
Risk Factors
The risk for a womans pregnancy to be affected by
Down syndrome is based on a variety of factors,
including maternal age and genetics. When trisomy 21
is caused by nondisjunction, a womans risk is af-
fected strongly by maternal age. With advancing
maternal age, a womans risk of having a child with
Down syndrome or another chromosomal abnormality
increases significantly.8 Because the majority of preg-
nancies occur in women under age 35, advanced
maternal age is not a significant risk factor in most
cases of Down syndrome, and most children with
Down syndrome are born to women under the age of
35. However, as the age at which women become
pregnant has increased, the number of fetuses with
trisomy 21 has also increased.9 Down syndrome due to
translocation occurs independent of maternal age and
may be inherited from either parent.10 Recent studies
suggest that 16 to 18% of spontaneous abortion fetuses
have trisomy 21.11
Recurrence Risk
Similar factors affect recurrence risk in future preg-
nancies for women who have previously given birth to
an infant with Down syndrome. Previous history of
trisomy can increase a womans risk for a recur-
rence.12 In Down syndrome due to nondisjunction
trisomy 21, the chance of recurrence is around 1% for
younger women and approximates the age-related risk
for older women.13 When Down syndrome occurs due
to translocation, the recurrence risk depends on the
type of translocation. In most cases, the recurrence risk
for de novo translocations is similar to that of the
general population but may be slightly higher in some
situations.10 When a translocation is inherited from a
parent, the recurrence risk can be much higher, de-
Curr Probl Pediatr Adolesc Health Care, September 2008
pending on the chromosomes involved in the translo-
cation. Because of the complexities involved in the
determination of recurrence risk, genetic counseling is
recommended for all families interested in understand-
ing their risk for future pregnancies.
Prenatal Screening and Diagnosis
Prenatal Screening
The goal of prenatal screening is to better assess a
womans risk of having a child with Down syndrome.
Screening tests are not diagnostic but rather indicate
the likelihood of the fetus being affected (for example,
there is a 1 in 353 chance of having a child with
Down syndrome). Maternal serum screening methods
utilize biochemical markers such as maternal serum
alpha-fetoprotein (MSAFP), human chorionic gonad-
otropin (hCG), and estriol that are present in abnormal
levels in pregnancies affected by certain conditions.
When available, the results of serum screening tests
can be combined with maternal age to determine a
more precise adjusted risk than that determined by age
alone. However, it is important to remember that a
low-risk assessment does not eliminate the chance of
the disorder occurring. Definitive testing for genetic
disorders can only be achieved during the pregnancy
by invasive procedures such as amniocentesis or
chorionic villus sampling (CVS) or by karyotype after
birth.
In the past, maternal age has been used to determine
whether women received prenatal screening or inva-
sive testing. Current recommendations suggest that
maternal serum screening for chromosomal abnormal-
ities be offered to all pregnant women regardless of
maternal age.14 It has recently been recommended that
invasive testing such as amniocentesis or CVS be
available to all women.8 It is not clear that the latter
recommendation has been universally accepted into
practice.
Specific Screening Tests
The triple screen became available in the 1980s as
a maternal serum screen offered during the second
trimester of pregnancy. The triple screen consists of
three biochemical markers: MSAFP, hCG, and estriol.
Decreased levels of MSAFP are associated with in-
creased risk for trisomy, whereas increased levels are
associated with neural tube defects. In Down syn-
drome, hCG levels may be increased and estriol may
Curr Probl Pediatr Adolesc Health Care, September 2008
be decreased.15 When combined with maternal age-
related risk, the detection rate or sensitivity for Down
syndrome using the triple screen is around 70%,
assuming a 5% false-positive rate.14 In the 1990s,
inhibin-A was added to the triple screen to form the
quad screen. With the addition of inhibin-A, the
sensitivity for detecting Down syndrome by quad
screening has been estimated at around 80%.16 Be-
cause these tests provide a risk assessment and are
nondiagnostic, careful genetic counseling is needed to
assure that parents understand the meaning of these
results.
Some of the most recent developments in prenatal
screening for Down syndrome involve markers that
can be used early in the pregnancy, during the first
trimester. The maternal serum markers pregnancy-
associated plasma protein-A and hCG have been found
to be reliable screening tools in the first trimester.17
The determination of nuchal translucency (NT), a
collection of fluid at the back of the neck, can be
performed prenatally by ultrasound. Increased NT has
been associated with chromosomal and structural ab-
normalities in the fetus. Ultrasound measurements of
NT during a specific window in the first trimester have
been standardized such that risk for Down syndrome
can be reported.14 However, determination of NT is a
specialized skill requiring certification, and NT testing
is not universally available. The sensitivity of first
trimester screening using NT, pregnancy-associated
plasma protein-A, and hCG ranges between 82 and
87%, depending on gestational age, assuming a 5%
false-positive rate.11
Ultrasound can also be used to detect abnormalities
seen with greater frequency in chromosomal disorders.
For example, structural abnormalities such as congen-
ital heart disease and duodenal atresia, seen with
greater frequency in Down syndrome, may be noted
prenatally. Other more subtle findings, such as short-
ened humerus and femur length, echogenic focus in
the bowel or heart, and mild renal pelviectasis, are a
few of many soft markers for Down syndrome.18
The presence of these subtle signs should be consid-
ered in combination with other risk factors such as
maternal age and, if available, maternal serum screen-
ing results.14
Definitive Testing
Abnormal screening test results can be confirmed
prenatally by invasive testing that harvests fetal cells
for genetic testing. During the second trimester, this is
243
achieved by amniocentesis, which is performed be-
tween 15 and 20 weeks gestation. As an invasive
procedure, amniocentesis is associated with some
degree of risk to the fetus and pregnant woman. The
risk of pregnancy loss with amniocentesis has tradi-
tionally been quoted at 1/200, although more recent
estimates done in the era of improved ultrasound
technology suggest excess fetal loss rate associated
with second trimester amniocentesis is 0.16%.19 Dur-
ing the first trimester, CVS can be used to confirm
screening results. CVS can be performed earlier than
amniocentesis, between 10 and 12 weeks gestation.
The overall risk of pregnancy loss after CVS has
traditionally been quoted up to 1/100.20 More recent
information suggests that that the risk may be similar
to amniocentesis (0.25 to 0.5%) when CVS is per-
formed by experienced clinicians.8
The choice of whether to participate in screening or
invasive testing ultimately lies with the individual
family. Some families may decline screening because
the results would not change their decision about the
pregnancy. For other families, knowing the informa-
tion before the birth of their baby can provide reas-
surance and preparation. In some cases, detection of
Down syndrome during the pregnancy can help antic-
ipation of medical problems often associated with
Down syndrome. Congenital heart disease is an exam-
ple of a medical problem that may be closely moni-
tored in the fetus with Down syndrome. When the
results of screening procedures have been confirmed,
some families may choose termination or adoption.
Parents of children with Down syndrome and disabil-
ity advocates have raised concern that early prenatal
diagnosis may increase a womans likelihood of
choosing termination. As prenatal screening has be-
come more sophisticated, the number of pregnancies
terminated due to trisomy 21 has increased, and
subsequently, the incidence of Down syndrome has
decreased.21
Clinicians involved in counseling parents about test
results should take care to present information in a
sensitive and unbiased manner. Often the focus be-
comes a description of the medical and psychosocial
challenges faced by individuals with Down syndrome.
Thanks to programs such as Early Intervention, school
inclusion, and improved health care, many more op-
portunities are now available for children and adults
with Down syndrome. The availability of balanced
and up-to-date information allows parents to make an
244
informed and personal choice about the pregnancy and
the future of their family.
Informing Parents
A relatively common scenario encountered by pri-
mary care clinicians is that of the newborn infant with
features suggestive of trisomy 21. Because of the
characteristic physical features seen in babies with
Down syndrome, the diagnosis may be highly sus-
pected; in other cases the clinician may be less sure.
Both scenarios are difficult for clinicians and can have
significant impact on families.
Despite the recent advances in prenatal screening,
many parents will learn of their childs diagnosis after
delivery.22 Informing a family of suspected Down
syndrome often invokes uncomfortable feelings for
both clinicians and parents. Clinicians may be unsure
of their diagnosis or may dislike giving bad news.
When providers try to avoid sharing their concerns
with the family or rush through the information,
interactions may come across as insensitive or uncar-
ing. When parents hear their doctors concerns, they
may initially feel that their hopes and dreams for their
child have been irreparably altered; the diagnosis of a
genetic disorder is often experienced as a loss for
families. In truth, it is impossible to know how an
individual family member will react to the news, and
providers should be prepared for each family to react
in their own way.
Clinicians are encouraged to share their concerns
with families as soon as they are able, and in most
cases, this discussion will occur before diagnosis has
been confirmed or not confirmed by karyotype. It is
important for clinicians to be honest about their
concerns when a karyotype is ordered, as families who
are not informed ahead of time may be angry or
resentful when the final karyotype results indicate
Down syndrome. When discussing concerns with par-
ents, the environment should be private, comfortable,
and supportive, and clinicians should set aside ample
time to discuss the information. Care should be taken
to involve both parents, if possible, and to have the
baby in the room during the discussion. The most
appropriate introduction is almost always, Congratu-
lations on the birth of your baby. If the baby has been
named, it is helpful to refer to her or him by name to
accentuate the fact that this person is a new member of
the family. When meeting the family, the clinician can
highlight what seems to be going well for the newborn
and his or her parents. The clinician might then begin
Curr Probl Pediatr Adolesc Health Care, September 2008
Table 1. Key points to informing parents of a diagnosis of Down
syndrome
Tell the family as soon as possible, when the mother is settled
Choose a private setting with both parents and the baby present
together
Set aside ample time for the discussion
Emphasize that definitive testing (a karyotype) will be done to
confirm or exclude the diagnosis
Ask families what information would be helpful; have current,
printed information available
Avoid predictions about the future
Check back with the family to make sure their questions and
concerns have been addressed
Adapted from the National Down Syndrome Society Changing Lives: Down
Syndrome and The Health Care Professional (National Down Syndrome Society,
2006).
with Ive noticed a few features in your baby that
make me wonder about a condition called Down
syndrome. Id like to spend some time talking with
you about that. It is often helpful to examine the baby
with the family to highlight a few characteristics that
suggest Down syndrome. While the clinician may be
uncomfortable that the diagnosis has not yet been
confirmed, this uncertainty can allow the family im-
portant time to think about the possibility of the
diagnosis before the final results are determined by
karyotype.7
When hearing the news about Down syndrome,
families appreciate a careful and balanced explanation.
The pacing of the information should be tailored to the
parents: pausing to ask what questions do you have at
this point? or am I going too fast for you? can be
helpful. The publics understanding of Down syn-
drome has changed significantly in the last decades,
and parents may have personal knowledge of a person
with trisomy 21. Asking a family what types of things
do you know about Down syndrome? can be helpful
in assessing a parents level of knowledge and under-
standing. Clinicians need not be overly negative or
pessimistic and should avoid making predictions about
the future. A positive and balanced approach can
explain the challenges faced by children with Down
syndrome but also emphasizes the joys of loving and
raising a child. Generalities can be offered when the
parents inquire but should always be phrased with the
understanding that all children have different poten-
tials, and children with Down syndrome have a wide
range of abilities. A summary of key points to consider
when discussing concerns regarding Down syndrome
with parents is presented in Table 1.
Each family will respond differently to the news
shared with them about their new baby. Some will be
Curr Probl Pediatr Adolesc Health Care, September 2008
Table 2. Welcome to Holland by Emily Perl Kingsley
I am often asked to describe the experience of raising a child with
a disabilityto try to help people who have not shared that
unique experience to understand it, to imagine how it would feel.
Its like this . . .
When youre going to have a baby, its like planning a fabulous
vacation tripto Italy. You buy a bunch of guidebooks and make
your wonderful plans. The Coliseum. The Michelangelo David. The
gondolas in Venice. You may learn some handy phrases in
Italian. Its all very exciting.
After months of eager anticipation, the day finally arrives. You pack
your bags and off you go. Several hours later, the plane lands.
The stewardess comes in and says, Welcome to Holland.
Holland?!? you say. What do you mean Holland?? I signed up for
Italy! Im supposed to be in Italy. All my life Ive dreamed of going
to Italy.
But theres been a change in the flight plan. Theyve landed in
Holland and there you must stay.
The important thing is that they havent taken you to a horrible,
disgusting, filthy place, full of pestilence, famine and disease.
Its just a different place.
So you must go out and buy new guide books. And you must learn
a whole new language. And you will meet a whole new group of
people you would never have met.
Its just a different place. Its slower-paced than Italy, less flashy
than Italy. But after youve been there for a while and you catch
your breath, you look around . . . and you begin to notice that
Holland has windmills . . . and Holland has tulips. Holland even
has Rembrandts.
But everyone you know is busy coming and going from Italy . . . and
theyre all bragging about what a wonderful time they had there.
And for the rest of your life, you will say Yes, thats where I was
supposed to go. Thats what I had planned.
And the pain of that will never, ever, ever, ever go away . . .
because the loss of that dream is a very very significant loss.
But . . . if you spend your life mourning the fact that you didnt get
to Italy, you may never be free to enjoy the very special, the very
lovely things . . . about Holland.
1987 by Emily Perl Kingsley. All rights reserved. Reprinted by permission of
the author.
angry, and clinicians should be prepared for that anger
to be directed toward them. Others may be sad or
despondent, or express denial that Down syndrome is
a possibility. Acknowledging the normalcy of these
varied reactions can be helpful for families as they
begin to better understand their feelings. Clinicians are
encouraged to consider one parents perspective on
learning that her child has Down syndrome (Table 2).
Regardless of the familys reactions, the clinician
should reassure parents that they will continue to
provide support for the family. Consideration of a
private, rather than shared, hospital room for the new
mother is recommended. Checking back with the
family later that day, throughout the hospital stay, and
soon after discharge can be particularly helpful.
Clinicians are encouraged to have resources on
Down syndrome readily available in the newborn
245
nursery and their practices. Parents of newly diag-
nosed infants value current materials on Down syn-
drome; printed materials that the family can take home
are recommended.22 Information can be obtained from
organizations such as the National Down Syndrome
Society (http://www1.ndss.org/) and the National
Down Syndrome Congress (http://www.ndsccenter.
org/). Local parent support groups can also serve as an
important resource, allowing families to speak with
other parents of children with Down syndrome. Refer-
ral to a regional Down Syndrome Center can provide
families with focused, subspecialty care. Information
on the locations of regional Down syndrome centers
can be found on the National Down Syndrome Con-
gress website. Health supervision guidelines for chil-
dren with Down syndrome have been developed by the
American Academy of Pediatrics and are an excellent
resource for clinicians who care for children with
Down syndrome.6
Clinical Features
Physical Features
Examination of the newborn infant may reveal
characteristic facial features of Down syndrome in-
cluding a flat, broad face, flat nasal bridge, flat facial
profile, and up-slating palpebral fissures. Many of
these features are due to midfacial hypoplasia. In
children with lighter colored eyes, Brushfield spots
can be seen in a ring-like pattern in the iris. They
appear as a stellate pattern of white to light yellow
speckles near the periphery of the iris. They consist of
strands of connective tissue and do not affect the
vision or functioning of the eyes. An epicanthal fold,
which is a skin fold that partially covers the medial
canthus of the eyes, is often evident. Outer ears are
smaller than normal, can be dysplastic, and are often
low-set in relation to the other facial features. The
tongue may protrude from the mouth, which can be
smaller than normal.
Certain features can be noted in the head, neck,
trunk, and extremities. The head is often brachyce-
phalic in shape, sometimes with pronounced plagio-
cephaly. The neck can be short, with thick or redun-
dant skin at the nape of the neck. Examination of the
extremities may reveal the following: single palmar
crease, previously referred to as a simian crease, short
fifth fingers with or without clinodactyly (curvature of
the finger), and a wide space between the first and
246
second toes, also known as sandal-foot deformity.
This is often accompanied by a longitudinal crease on
the sole of the foot extending from the gap between the
first and second toes to the ball of the foot. Hypotonia
is often present at birth and can be seen as a floppy
infant. The presence of many of the classic physical
features of Down syndrome often leads to its sus-
pected diagnosis at birth.
Other features may not become evident until the
child grows older. For example, the anterior fontanelle
is usually larger and takes longer to close, often
remaining open until the second birthday. Teeth may
not erupt until well after the first birthday. Deciduous
teeth often erupt in an unusual pattern or order and
may be small or unusually shaped. Delays in motor
development often do not appear until the latter half of
the first year of life. It is at that time that the infant
does not reach motor milestones, such as sitting up,
creeping, crawling, and pulling to stand, on time. It is
rare for a child with Down syndrome to start walking
independently before the age of 18 months but not
unheard of. Most children with Down syndrome walk
by the age of 2 to 2 years.
Hypotonia and hyperflexibility of the joints allow
children with Down syndrome to sit in unusual posi-
tions. Many can sit comfortably in the W or reverse
tailor position. Others can transition from the sitting to
crawling position and vice versa by simply swinging
their legs out to the side and bringing them around to
the front or back. Children with Down syndrome are
known to sleep in unusual positions, oftentimes with
their heads resting on their legs or between their legs.
Medical Complications
Trisomy 21 is associated with a number of medical
complications; some are apparent at birth and others
may develop across the lifespan.
Cardiac. Congenital heart defects occur in an esti-
mated 40 to 60% of children with Down syndrome. In
a large study of 227 patients with Down syndrome in
the Atlanta area, 44% were found to have a congenital
heart defect.23 Most common among these include
atrioventricular septal defect, also known as atrioven-
tricular canal or endocardial cushion defect, atrial
septal defects, and ventricular septal defects. These
result in incomplete closure of the septum dividing the
left and right sides of the developing heart early in
gestation. The defects range from very small and
insignificant to a nearly absent septum. In the latter
case, the atrial-ventricular valves do not form nor-
Curr Probl Pediatr Adolesc Health Care, September 2008
mally. Instead of two separate valves, there is a single
large opening bridged by a common atrioventricular
canal, which allows mixing of blood from all four
chambers.24 If large enough, this will allow a left-to-
right shunt of blood through the heart. This will
increase blood flow through the pulmonary artery,
resulting in increased pulmonary artery pressure and
subsequent pulmonary hypertension.
In a large study by Freeman of 227 children with
Down syndrome who had congenital heart defects, the
following types were found:
Atrioventricular septal defects: 45%
Ventricular septal defects: 35%
Isolated secundum atrial septal defect: 8%
Persistent patent ductus arteriosus: 7%
Tetralogy of Fallot: 4%
Other: 1%23
Even children who seem asymptomatic at birth and
do not have a murmur could have a significant defect.
If there is increased pulmonary vascular resistance, the
left-to-right shunt may be minimized, thus preventing
early heart failure. However, if left undetected, this
condition could lead to persistent pulmonary hyper-
tension and irreversible pulmonary vascular changes.
Generally, surgery to correct the heart defect is de-
layed until the infant is larger and strong enough to
tolerate the surgery, which is usually done at 6 to 9
months of age. Most children do very well and thrive
following their surgery.
Gastrointestinal. Children with Down syndrome are
at greater risk for a host of gastrointestinal disorders
ranging from congenital defects to disorders that
manifest later in life. Congenital defects include duo-
denal atresia or stenosis with or without annular
pancreas, duodenal web, tracheoesophageal fistula,
and pyloric stenosis. Imperforate anus and Hirsch-
sprung disease are also more common in Down
syndrome than in the general population. Gastroesoph-
ageal reflux disease (GERD) is commonly seen in
children with Down syndrome and can be severe
enough to result in aspiration of stomach contents.
This may result in respiratory symptoms such as
persistent coughing, wheezing, and pneumonia. In-
fants with oral-motor difficulties may present with
choking and gagging on feedings as well as the
respiratory symptoms mentioned. If an infant with
Down syndrome experiences frequent vomiting and
spitting up, even several hours after a meal, GERD
should be considered. An upper gastrointestinal (GI)
Curr Probl Pediatr Adolesc Health Care, September 2008
series or a pH probe study can be helpful in making the
diagnosis of GERD. A video swallow study should be
done in a child who is having difficulties with oral
feedings and has respiratory symptoms including
coughing, wheezing, and pneumonia. They may be
experiencing silent aspiration of liquids and may need
to have liquids in their diet thickened.
Celiac disease occurs more commonly in the Down
syndrome population. One study showed 1 in 14
patients or 7% of children with Down syndrome had
celiac disease.25 Chronic constipation is a common
complaint in the Down syndrome population. One
theory suggests that it may be related to the general-
ized hypotonia that is usually seen in Down syndrome.
If it does not improve with standard treatments such as
increased fiber and fluids in the diet or stool softeners,
other causes should be considered. These include
hypothyroidism and Hirschsprung disease. Referral to
a pediatric gastroenterologist for further studies may
be in order.
The prevalence of obesity in the Down syndrome
population is higher and may be due in part to a
reduced resting metabolic rate.26 Many adolescents
have difficulty controlling their appetites. Counseling
parents about the risks of overeating should begin
early and be mentioned at every well child visit.
Parents may benefit from meeting with a nutritionist
who can give them specific dietary guidelines on
caloric needs and portion sizes. In addition, an active
lifestyle with routine exercise is recommended for the
whole family. Children should be encouraged to par-
ticipate in recreational activities such as swimming,
dancing, walking, and playing outdoors. Sedentary
activities including television viewing should be
limited.
Ophthalmologic. Children with Down syndrome
frequently experience vision problems and ophthalmo-
logic disorders. Most common among these are refrac-
tive errors, such as myopia, hyperopia, and astigma-
tism. These can be corrected with glasses if the child
is willing to wear them. Other common eye disorders
include strabismus and nystagmus. Congenital cata-
racts can lead to blindness if left untreated. Other
serious eye disorders include glaucoma and keratoco-
nus, which is when the cornea bulges outward like a
cone. Blocked tear ducts, or nasolacrimal duct steno-
sis, is commonly seen and can lead to increased tear
stasis and conjunctivitis.
Otolaryngologic. The underlying defect of midfacial
hypoplasia is felt to be responsible for the many ear,
247
nose, and throat medical problems experienced by
children with Down syndrome. Many children expe-
rience recurrent ear infections or persistent middle ear
effusions. They may be candidates for early placement
of pressure equalization tubes to prevent hearing loss.
Unfortunately, the ear examination can be difficult in
these children because of the narrow ear canals and
cerumen obscuring visualization of the tympanic
membranes. Early referral to an otolaryngologist is
recommended. Hearing loss is very common, occur-
ring in at least 50% of people with Down syndrome at
some point in their lives. Hearing loss can be unilat-
eral, bilateral, conductive, sensorineural, or mixed. It
ranges from mild, moderate, or severe, to profound.
Hearing loss can be congenital or acquired. Some
children may be candidates for cochlear implants.
Shott and coworkers found that early and aggressive
treatment of chronic ear disease can greatly reduce
hearing loss in children with Down syndrome.27
The narrow nasal passages and sinuses predispose
these children to sinusitis and nasopharyngitis. Parents
often complain that their child always sounds con-
gested. Symptoms often improve with symptomatic
treatment. Some children benefit from adenoidectomy
and/or tonsillectomy. Enlarged tonsils as well as other
causes for upper airway obstruction can lead to ob-
structive sleep apnea. Primary care physicians should
ask about signs of obstructive sleep apnea at each well
child checkup. These include snoring, pauses in the
breathing pattern, restlessness while asleep, sleeping
in unusual positions, and daytime fatigue or drowsi-
ness. If a parent endorses these symptoms, the child
should undergo a sleep study in a sleep laboratory that
is designed to serve children. If such a study is not
easily attainable, the child should be referred to an
otolaryngologist for further evaluation and possible
treatment of causes of upper airway obstruction if
present.
Endocrine. Thyroid dysfunction, particularly hypo-
thyroidism, is relatively common in individuals with
Down syndrome, occurring in approximately 17% of
the population.28 Symptoms of hypothyroidism in-
clude slow growth, impaired cognition, and weight
gain, which may be attributed to the Down syndrome
itself. Therefore it is recommended that children be
screened with a free T4 level and a thyroid stimulating
hormone (TSH) level at birth, at 6 and 12 months of
age, and then yearly thereafter.29 Some children dem-
onstrate an elevated TSH level with normal T4 levels.
If the TSH level is only mildly elevated, it should be
248
repeated before initiating treatment because in many
instances the elevation is transient and will normalize
spontaneously. Hyperthyroidism can also be seen.
Diabetes mellitus occurs with higher frequency in the
Down syndrome population.
Hematologic. Childhood leukemia is more common
in the Down syndrome population compared with the
general population. The risk of leukemia in Down
syndrome is 1 to 1.5%.30 Among children with Down
syndrome, acute lymphoblastic leukemia is more com-
mon in children over 1 year, while acute myelogenous
leukemia is more common in infants. The diagnosis
and type of leukemia is confirmed by bone marrow
biopsy in children who present with clinical features
and blood counts that support a diagnosis of leukemia.
Acute lymphoblastic leukemia is now a very treatable
disease and 60 to 70% of children with Down syn-
drome have a successful course of treatment. Interest-
ingly, the cure rate for acute myelogenous leukemia is
higher in children with Down syndrome than in
children without Down syndrome.24 Newborn infants
with Down syndrome are prone to transient myelopro-
liferative disorder, also known as leukemoid reaction,
transient abnormal myelopoiesis, or transient leuke-
mia. It is characterized by the presence of blast cells in
the peripheral blood. Thrombocytopenia or thrombo-
cytosis can also occur. In most cases, this disorder
resolves spontaneously in 2 to 3 months. However, in
some cases it can progress to more severe disease such
as acute megakaryoblastic leukemia within the first 4
years of life.
Immunologic. Children with Down syndrome are
more prone to recurrent respiratory and systemic
infections. This may be due to deficiencies in some
immunoglobulin levels. IgA deficiency can be seen in
individuals with Down syndrome as can deficiencies
of IgG subclasses. Individuals with Down syndrome
also seem to be more susceptible to autoimmune
diseases such as thyroid disease, diabetes, and celiac
disease.
Orthopedic. Atlantoaxial instability is defined as
increased mobility of the cervical spine at the level of
the first and second vertebrae. It can lead to subluxa-
tion of the cervical spine. Approximately 10 to 30% of
individuals with Down syndrome have this condi-
tion.31 The majority of them are asymptomatic, while
10% of individuals who have the condition have
symptoms including neck pain, torticollis, changes in
gait, changes in bowel or bladder control, or other
signs of paralysis or weakness.32
Curr Probl Pediatr Adolesc Health Care, September 2008
 Diagnosis of the condition is made by lateral neck
film taken with the neck in flexion and extension. Plain
films may need to be taken under fluoroscopy if the
child is less than cooperative. Measurements are made
between the anterior arch of C1 and the odontoid
process of C2. Distances greater than 5 mm are
considered abnormal. If the child is experiencing
symptoms of spinal cord compression, they should be
referred to a pediatric neurosurgeon promptly for
further evaluation. Further imaging, such as computed
tomography or magnetic resonance imaging of the
cervical spine and spinal column, may be helpful.
Spinal fusion is performed in more significant cases.
In other cases, the child may be followed with periodic
spine films.
Children with Down syndrome are prone to other
orthopedic problems as well. Because of ligamentous
laxity and hypotonia, which are almost universal in
Down syndrome, these individuals are prone to dislo-
cated joints. This can occur in the hip, knee, shoulder,
elbow, or thumb. Repeated dislocations of a joint may
lead to early degeneration of the joint. This can be a
painful process that leads to decreased range of motion
and mobility. Some individuals experience exercise
intolerance and have decreased stamina compared
with peers. Other orthopedic conditions seen in Down
syndrome include genu valgus, over-pronation of the
ankle, flat feet, and scoliosis.
Psychiatric and Behavioral Disorders. Psychiatric
disorders are more prevalent in the Down syndrome
population than in the general population. Studies
estimate that 13 to 17.6% of children with Down
syndrome have a psychiatric disorder.33 These include
common psychiatric disorders such as depression,
anxiety, obsessive-compulsive disorder, schizophre-
nia, and anorexia nervosa. Assessing an individual
with Down syndrome for a psychiatric disorder is
more challenging due to impairments of communi-
cation skills, lack of insight, and maladaptive be-
haviors in response to internalizing factors. Any
change in a persons level of function, whether it be
in communication skills or self-help skills, warrants
investigation. It is imperative that medical condi-
tions be considered since they are often be treatable.
For example, behavior changes may be caused by
hypothyroidism, loss of hearing, loss of vision,
obstructive sleep apnea, or even seizures. A careful
history and physical examination should help to
narrow the differential diagnosis. Once medical
conditions have been excluded, a primary psychiat-
Curr Probl Pediatr Adolesc Health Care, September 2008
ric disorder should be explored. A simple mental
status examination should be performed. It is often
helpful to interview caregivers for more details
regarding the persons behavior. Psychiatric consul-
tation can be very helpful in confirming a diagnosis
or in devising a treatment plan. Other disruptive
behavior disorders, such as attention deficit hyper-
activity disorder, oppositional defiant disorder, and
conduct disorder, can also be present. Autism spec-
trum disorders deserve mention because they occur
at higher rates in children with Down syndrome
compared with the general population. Current ev-
idence supports that autism affects 1 of every 150
children.34 In the Down syndrome population, esti-
mates put the prevalence to be between 5 and
10%.35 The onset of symptoms is often later than
what is typically seen in individuals without Down
syndrome.
Alzheimers disease or Alzheimer type dementia can
occur at a relative early age. They are characterized by
memory loss and the inability to learn new information
and a decline in intellectual skills. There are chal-
lenges to making this diagnosis in someone with
Intellectual Disability. In addition to changes in level
of functioning, the person may also exhibit neurolog-
ical signs including seizures, focal neurological signs,
incontinence, changes on electroencephalogram, trem-
ors, changes in sensory systems, and changes in gait or
mobility. Another well-known association between
Down syndrome and Alzheimers disease is that the
neuropathological abnormalities seen in patients with
Alzheimers disease can also be seen on examination
of the brains of individuals with Down syndrome who
did not exhibit the symptoms. These neuropathologi-
cal findings include senile plaques and neurofibrillary
tangles.36
Growth Patterns in Children with
Down Syndrome
Children with Down syndrome have a slower rate of
growth when compared with their typical peers. The
decreased rate of growth noted in Down syndrome is
most pronounced in the periods of infancy and ado-
lescence. Children can have difficultly with weight
gain early in life that can be related to low tone and to
feeding difficulties and may be complicated by medi-
cal conditions, such as heart disease, that can impact
weight gain. Puberty tends to appear relatively early in
249
Table 3. Developmental milestones Table 4. Self-help skills
Children with Down Children with
syndrome Normal children Down syndrome Normal children
Milestone Skill
Average Range Average Range Average Range Average Range
(mo) (mo) (mo) (mo) (mo) (mo) (mo) (mo)
Smiling 2 1.5-4 1 0.5-3 Eating
Rolling over 8 4-22 5 2-10 Finger-feeding 12 8-28 8 6-16
Sitting alone 10 6-28 7 5-9 Using spoon/fork 20 12-40 13 8-20
Crawling 12 7-21 8 6-11 Toilet training
Creeping 15 9-27 10 7-13 Bowel 42 28-90 29 16-48
Talking, words 16 9-31 10 6-14 Bladder 48 20-95 32 18-60
Standing 20 11-42 11 8-16 Dressing
Walking 24 12-65 13 8-18 Undressing 40 29-72 32 22-42
Talking, phrases 28 18-96 21 14-32 Putting clothes on 58 38-98 47 34-58
From Down Syndrome: Growing and Learning. Dr. Siegfried Pueschel 1978. From Down Syndrome: Care of the Child and Family, William I. Cohen,
Published by Andrews McMeel Publishing. Reprinted by permission. Developmental Behavioral Pediatrics, eds. Levine, Carey, Crocker, 3rd ed.,
Copyright Elsevier. Reprinted by permission.

children with Down syndrome, but there continues to

be a relatively decreased growth rate during puberty.
Over their lifespan, people with Down syndrome tend
to be overweight compared with the general popula-
tion. This trend often begins in early childhood and
may persist through adolescence and into adulthood.
Overweight in Down syndrome, as in the general
population, is likely multifactorial, with contributions
from biological and environmental factors.37 Of
course, maintaining healthy weight can be influenced
by healthy diet and physical activity. Family education
regarding the value of healthy dietary habits and
routine physical activity for children with Down syn-
drome is important.
Growth charts have been developed to reflect the
expected growth patterns for children with Down
syndrome. Developed by Cronk and coworkers and
published in 1988, the Down syndrome growth charts
were based on 4650 measurements made on 730
children with Down syndrome who were home-
reared.38 Children with Down syndrome who were
raised in institutions had slower growth rates, were
shorter overall, and also tended to have larger weights
in comparison with children who were home-
reared.39 The American Academy of Pediatrics has
endorsed the use of Down syndrome specific growth
charts in their 2001 publication, Health Supervision
for Children with Down Syndrome.6 These customized
growth charts have been adapted and published online
at www.growthcharts.com and can also be accessed on
line at the National Down Syndrome Society at www.
ndss.org. These charts have been broken down into
English and metric versions with separate charts for
weight, height, and head circumference. They are
user-friendly and easy to download.
These patterns of growth in children with Down syn-
drome are similar across cultures. However, there are
differences in percentiles developed based on population
studies in other countries. Differences in growth vary
among countries in people with Down syndrome as it
does in the general population. Alternative charts have
been proposed and developed in several countries, in-
cluding the UK and Republic of Ireland40 and Saudi
Arabia.41 When monitoring growth of a child with Down
syndrome, as with any child, it is important to consider
their cultural background.
Developmental Patterns in Children
with Down Syndrome
Infancy and Early Childhood
In comparison with typically developing peers, chil-
dren with Down syndrome have delays across develop-
mental domains including language, gross motor, fine
motor, cognitive, personal-social, and self-help skills.
Expressive language tends to be more delayed in com-
parison with receptive language and cognitive skills.29
While there is significant variation in acquisition of
milestones in typically developing children, this variation
is even more pronounced in children with Down syn-
drome. Ranges for developmental milestones have been
published for children with Down syndrome and offer
some guidance in terms of developmental expectations
(Tables 3 and 4). This information can be useful when
discussing the wide range of acquisition of developmen-
tal milestones with parents.29,42
Acquisition of developmental milestones can be
influenced by multiple factors. Historically, children

250 Curr Probl Pediatr Adolesc Health Care, September 2008

with Down syndrome were often raised in institutions.
Developmental outcomes improve substantially when
children are raised in the home environment and
receive early intervention services.43 Milestone ranges
in noninstitutionalized children with Down syndrome
demonstrate the variability in early development that
is now well accepted.42
Further findings have established the important role
that environment plays in early development in chil-
dren with Down syndrome. Socioeconomic status and
parental education are significantly associated with
acquisition of early milestones and variation in abili-
ties of persons with Down syndrome.44,45 There is also
documentation of the positive impact of early stimu-
lation and early intervention on early development.46
Gender may affect developmental outcomes. For ex-
ample, some studies have reported that females with
Down syndrome tend to have higher abilities than
males, although this has not been reported for all
cohorts studied.45,47,48 Most children with Down syn-
drome will grow up to have mild to moderate cogni-
tive impairment and a few will have severe cognitive
impairment.6
Early acquisition of milestones in children with
Down syndrome is also affected by medical factors.
For example, children with significant heart disease
are usually more delayed in acquisition of early motor
milestones compared with children with Down syn-
drome and no heart disease. In addition, children with
Down syndrome often have pronounced hypotonia
that affects all areas of development. For example,
hypotonia can affect development of early postural
behaviors such as sitting and crawling. Postural con-
trol impacts the childs ability to interact with the
environment and to develop skills such as early
fine-motor, problem-solving, and feeding skills. Low
tone also slows the acquisition of gross motor skills.
Childhood
Language Development and Cognition. Decades of
systematic research regarding the learning and lan-
guage profile of individuals with Down syndrome can
provide useful information for families and clinicians
involved in the care of individuals with Down syn-
drome. While the research has demonstrated that
children with Down syndrome share some typical
cognitive, language, memory, and behavior character-
istics, researchers caution that caregivers and service
providers must take an individualized approach to the
education of individuals with Down syndrome.49 For
Curr Probl Pediatr Adolesc Health Care, September 2008
example, language is an integral component of cogni-
tion50 and language affects any childs performance
during cognitive testing, so the choice of assessment
tools and educational practices should take this into
account.
The overall theme to convey to families is the wide
range of variability in achievement levels for individ-
uals with Down syndrome. This variation mandates an
individualized educational approach that continually
monitors for areas of strength and weakness. Chapman
noted that the average IQ score for people with Down
syndrome is around 50, ranging from 30 to 70.51
Although IQ describes the cognitive abilities of an
individual with Down syndrome in terms of a single
intelligence score, it is likely unhelpful for educational
purposes.52 In terms of age equivalent, individuals
with Down syndrome typically reach a mental age of
6 to 8 years old by adulthood.49 The delayed cognitive
development of children with Down syndrome com-
pared with typically developing peers becomes most
evident beginning at 2 years of age.53 The discrepancy
between typical and delayed development becomes
more apparent as delayed children become older
because children with delays learn more slowly their
same-aged peers.
There is compelling research that supports expressive
language deficits in individuals with Down syndrome
with relative receptive language strengths.50,53,54 This
suggests that individuals with Down syndrome can
understand more than they can convey. Infants and
toddlers with Down syndrome show a slower tran-
sition from babbling to speech, and, although single
words and two-word phrases may be acquired at a
time consistent with cognitive ability, expressive
language delays progressively increase relative to
receptive language and cognitive skills.54 Intelligi-
bility of speech remains an area of concern throughout
life. This observation may be the result of midface
hypoplasia, average size tongue, and low muscle tone
in the lips and tongue.55 Kumin suggested there might
be an underdiagnosis of verbal apraxia in very young
children with Down syndrome. After creating and
using a parent questionnaire to identify verbal apraxia,
her findings suggested that treatment should begin
when children are first learning to speak to possibly
reduce intelligibility issues later in life.55
Individuals with Down syndrome also experience
specific memory deficits in excess of their general
cognitive disabilities.56 Researchers have described
poor verbal short-term memory compared with visual-
251
Table 5. Medical complications and potential resulting behaviors
Medical complication
Hypotonia Fatigue
Lack of coordination
Sensory impairment Nature of task is more difficult and individual may experience failure
Sleep difficulties Irritability
Speech delay Frustration and resistance
Decreased understanding
Cardiac problems Fatigue
Discomfort
Surgery risks and recovery
Gastrointestinal issues Fatigue
Discomfort
Thyroid dysfunction Mood disturbances
spatial short-term memory.57 For example, individuals
with Down syndrome performed worse on a verbal
short-term memory task that required them to repeat a
series of numbers the examiner told them than on a
visual short-term memory task. In this task, they had to
tap a series of blocks that the examiner tapped.
Individuals with Down syndrome have also been
found to demonstrate intact implicit (ie, procedural)
memory versus poor explicit (ie, declarative) mem-
ory.56,58 Chapman investigated the possible interfer-
ence of poor verbal short-term memory on the acqui-
sition of expressive language.59 She found poor verbal
memory and problems with vocabulary development
for both individuals with Down syndrome and typi-
cally developing peers. Moreover, in comparison to
poor verbal short-term memory, individuals with
Down syndrome displayed higher visual-motor skills
(eg, drawing, stacking blocks, and manual expression
such as sign language).52 Results of long-term mem-
ory deficit research have been inconsistent, with Car-
lesimo and coworkers56 reporting evidence for such an
impairment, while Jarrold and coworkers60 did not
find a specific verbal long-term memory deficit.
Behavioral Issues. Children with Down syndrome
are typically stereotyped as being happy, easy-going,
and social.61 Practitioners are cautioned not to allow
such stereotypes to overshadow the behavior problems
related to medical complications and other behavioral
characteristics that occur in the Down syndrome pop-
ulation. Although children with Down syndrome typ-
ically have fewer behavior problems compared with
matched controls with other disabilities such as Prader
Willi syndrome or individuals with nonspecific mental
retardation, studies have found the prevalence of
significant behavioral or emotional problems ranged
from approximately 20%62,63 to 55%.64 In addition,
children with Down syndrome demonstrate more
252
Sequelae Potential resulting behavior(s)
Task avoidance
Aggression
Irritability
Increased dependency
Limited activity level
Decreased learning opportunities
Attention-seeking behavior
problem behavior than their typically developing sib-
lings65 and typically developing peers.66
Individuals with Down syndrome are prone to vari-
ous medical complications and behavioral character-
istics that can lead to problematic behavior (Table 5).
For example, hypotonia can lead to increased fatigue
followed by the avoidance of effort, which can result
in a limited activity level and decreased learning
opportunities. Fatigue and discomfort resulting from
chronic medical conditions can also lead to increased
dependency and attention-seeking behaviors such as
asking for help. Behavioral characteristics common
for individuals with Down syndrome include atten-
tion-seeking behaviors,62,67 attention problems,66 and
decreased speech intelligibility.55 Children with
Down syndrome avoid tasks more frequently than
typically developing children or children with other
forms of mental retardation by using attention-
seeking behaviors such as looking at the examiners
face and asking for help. Primary care clinicians are
in the pivotal role of offering anticipatory guidance
regarding the development of problem behaviors
that may result from these medical complications
and behavioral characteristics.
Older children (ages 10-13 years) with Down syn-
drome may display high rates of aggressive and
delinquent behavior, including argumentativeness, de-
manding attention, and swearing.62 More extreme
aggressive behaviors, such as getting into fights and
being physically aggressive, occurred in only 6 and
12% of the sample, respectively.62 Individuals aged 14
to 19, however, demonstrated lower levels of aggres-
sive and delinquent behaviors and instead demon-
strated more internalizing behaviors (eg, withdrawal,
anxiety/depression). These internalizing problems
have been hypothesized to be precursors to the levels
of depression often seen in adult Down syndrome
Curr Probl Pediatr Adolesc Health Care, September 2008
populations.63 Behaviors that remained consistent
across age groups included speech problems, stub-
bornness, disobedience, fears, and impulsivity.
Adolescence
Sexuality and Reproductive Issues. Parents of ado-
lescent girls with Down syndrome often have concerns
about reproductive issues even before their daughters
reach puberty. They are often concerned about man-
aging menstrual cycles and about the possibility of
pregnancy. They should be informed that women with
Down syndrome can be fertile. Options for contracep-
tion should be discussed when a girl reaches puberty.
Some forms of birth control may decrease or eliminate
menstrual cycles, which may be desirable for some
situations. A referral to an adolescent medicine spe-
cialist, one who practices gynecology, may be very
helpful. If not available, a gynecologist who has
experience working with women with special needs is
helpful.
Males with Down syndrome are generally infertile,
but there have been a few reports of offspring born to
affected men.68 Young men with Down syndrome
should be taught appropriate sexual behavior. Young
adults with Down syndrome can enjoy active social
lives and many become interested in having romantic
relationships.
Health Supervision Guidelines
Health supervision guidelines for children with
Down syndrome, developed by the American Acad-
emy of Pediatrics, were designed to supplement rou-
tine anticipatory guidance guidelines for healthy chil-
dren.6 The current guidelines encompass birth through
age 21 years and emphasize screening for specific
medical conditions more common in children with
Down syndrome. The guidelines outline screening and
other services to be done in accordance with the
medical home concept, including counseling about
educational options, community supports, diet and
exercise, and financial assistance. This type of medical
home care by the primary care clinician provides
critically important care coordination and advocacy
for families who are raising children with Down
syndrome.
Cardiac Recommendations
In the newborn period, the guidelines emphasize
cardiac evaluation due to the high incidence of cardiac
Curr Probl Pediatr Adolesc Health Care, September 2008
malformations in individuals with Down syndrome.
The most common lesions are atrial-septal defects
(45% of newborns with Down syndrome) and ventric-
ular-septal defects (35%).9 Children with Down syn-
drome have a tendency to develop increased pulmo-
nary resistance, which can mask clinical signs of
serious heart disease and place the child at risk for
pulmonary hypertension if not detected early. There-
fore, in the first few weeks of life, the infant should be
evaluated by a pediatric cardiologist or cardiologist
familiar with congenital heart lesions, even in the
absence of clinical signs of heart disease.6 The eval-
uation should include an echocardiogram.
Older adolescents and adults with Down syndrome
who were not found to have congenital defects as
infants can develop valve abnormalities later in life.
Most common among these include mitral valve pro-
lapse and aortic regurgitation. Young adults should
undergo clinical examination for signs of valvular
dysfunction. Subacute bacterial endocarditis prophy-
laxis is recommended for those individuals who meet
criteria of the American Heart Association.
Gastrointestinal Recommendations
Screening for congenital defects of the GI tract is not
routinely done at birth for children with Down syn-
drome. However, further investigation is warranted in
any infant who presents with the inability to tolerate
oral feedings. A double bubble sign seen on a plain
film of the abdomen is indicative of duodenal atresia.
Most of the congenital GI abnormalities can be surgi-
cally corrected. Due to an increased incidence of GI
malformations, the clinician should promptly evaluate
infants with Down syndrome who display symptoms
such as recurrent vomiting or severe constipation.
Because of an increased risk of developing celiac
disease, screening for celiac disease is recommended
at 2 years and should be repeated thereafter based on
symptoms. Symptoms of celiac disease include nau-
sea, abdominal distension, bloating, excessive gas,
diarrhea, steatorrhea, weight loss, poor weight gain, or
unexplained fatigue. Screening for celiac disease in-
volves checking serum tissue transglutaminase anti-
bodies or anti-endomysial antibodies. (A total IgA
level should also be checked to rule out IgA deficiency
that may affect the interpretation of the other antibod-
ies of the IgA subclass.) If these levels are elevated,
the child should be evaluated by a pediatric gastroen-
terologist for definitive diagnosis. If additional testing,
including endoscopy with small intestinal biopsy,
253
confirms the diagnosis of celiac disease, the child
should be placed on a gluten-free diet.
Ophthalmologic Recommendations
A careful eye examination should be done at birth
and at each well child checkup. If the red reflex is
absent or if strabismus or nystagmus is noted on
examination, the child should be referred to a pediatric
ophthalmologist. If the examination is normal, the
child should be referred for routine screening by an
ophthalmologist by 6 months of age and annually
thereafter.29
Otolaryngologic Recommendations
Hearing screening should be done at birth by either
otoacoustic emissions or by brainstem auditory evoked
response. Most states now require newborn hearing
screening for all infants. Even if a child passes his/her
newborn hearing screening, s/he should have routine
hearing screenings performed every 6 months up to 3
years of age or when a pure tone audiogram can be
obtained.29 Behavioral audiometry or play audiometry
is typically used in toddlers and preschoolers who
cannot yet indicate that they can hear pure tones. An
ear, nose, and throat consultation is warranted for any
child who fails a routine hearing screen or if a
caregiver has concerns about the childs hearing.
Endocrine Recommendations
Screening for thyroid dysfunction is mandated as
part of the newborn screening program in most states.
Because children with Down syndrome are at risk for
acquired hypothyroidism, free T4 and TSH levels
should be checked at 6 and 12 months of age and then
annually thereafter. Routine screening for diabetes is
not recommended. Of course, children who present
with symptoms of diabetes should be promptly eval-
uated for that disorder.6
Hematologic Recommendations
Leukemoid reactions and polycythemia can occur in
the newborn period; therefore, a screening complete
blood count is recommended.6 Beyond the neonatal
period, routine screening complete blood counts are
not recommended; while there is an increased risk of
leukemia in children with Down syndrome, it is still
relatively rare. However, if a child with Down syn-
drome presents with signs or symptoms of leukemia,
including lethargy, fever, infection, painful joints and
extremities, bleeding, loss of appetite, pallor, hepato-
254
splenomegaly, easy bruising, or enlarged lymph
nodes, a complete blood count should be ordered. A
complete blood count may also be performed in
adolescence to screen for anemia.
Immunologic Recommendations
If a child with Down syndrome has recurrent,
chronic infections, consider checking IgA and IgG
subclasses. While the total IgG level may be normal,
IgG subclasses 2 and 4 may be decreased and sub-
classes 1 and 3 may be increased.29 IgG subclass 4
deficiency can lead to recurrent bacterial infections.
An IgG subclass deficiency can be treated with intra-
venous gamma-globulin replacement therapy. Chil-
dren with Down syndrome should receive the current
recommended immunizations, including those for in-
fluenza and pneumococcal disease. Infants born pre-
maturely should receive respiratory syncytial virus
prophylaxis.
Orthopedic Recommendations
Children with Down syndrome have a tendency
toward excessive mobility between C1 (the atlas) and
C2 (the axis). Cervical spine X-rays in neutral, flexion,
and extension with measurement of the atlanto-dens
interval and neural canal width should be done at 3 to
5 years of age to screen for atlantoaxial instability or
subluxation. Special Olympics guidelines require such
screening before participation in high-risk sports such
as diving, swimming, etc.69
There is some controversy regarding the timing and
necessity of routine cervical spine films to check for
atlantoaxial instability. In the Health Care Guidelines
for Individuals with Down Syndrome: 1999 Revision,
the Down Syndrome Medical Interest Group recom-
mended screening individuals between the ages of 3
and 5 years with cervical spine films in neutral, flexed,
and extended positions.29 Some experts advise repeat-
ing the films before competing in Special Olympics or
participating in sports such as football, wrestling,
gymnastics, diving, horseback riding, or using a tram-
poline, while other experts believe that it is more
useful to check for signs and symptoms of atlantoaxial
instability on physical examination and order studies
when indicated.
Growth and Development Recommendations
Given the slower than expected rate of growth in
Down syndrome, it is important to plot children
with Down syndrome on Down syndrome specific
Curr Probl Pediatr Adolesc Health Care, September 2008
growth charts. These growth charts are available for
boys and girls between the ages of birth and 18
years. They include expected centiles for weight,
height, and head circumference. Using the appropri-
ate Down syndrome growth charts can provide
additional important information when monitoring
for other related comorbidities.
Early intervention for children with Down syndrome
continues to be a universal recommendation based on
its success with other populations with developmental
delays.70 Early intervention specialists can play an
important role in monitoring early development and
the acquisition of early developmental milestones in
children with Down syndrome. They can help families
understand the variation that is present in the devel-
opment of children with Down syndrome and can
monitor progress in development over time. It is
important to emphasize strengths in the child when
monitoring early development. Early intervention spe-
cialists can help families identify these strengths,
monitor developmental progress, and understand when
important milestones are emerging. Close monitoring
and an understanding of the pattern of early develop-
ment in children with Down syndrome can be helpful
to families as they work with their young child.
Interventions and Treatment
Educational
Because primary care clinicians are in regular con-
tact with their patients with Down syndrome, they
have a unique opportunity to monitor the educational
and service needs of the patient and family. It is
important that clinicians become familiar with the
federal mandates that require all individuals to receive
access to a free and appropriate public education as
indicated by the Individuals with Disabilities Educa-
tion Act.71 Individuals with Disabilities Education Act
covers children ages 0 through 2 (Part C, Early
Intervention) and 3 through 21 (Part B) by governing
how states and public agencies provide early interven-
tion, special education, and related services to children
with disabilities. Children with Down syndrome can
be identified at birth and should begin receiving Early
Intervention (EI) services immediately. Pediatricians
should refer families to the local agency for mental
retardation and developmental disabilities to obtain
access to EI services. These services typically are
provided until a child is 3 years of age.72 An Individ-
Curr Probl Pediatr Adolesc Health Care, September 2008
ualized Family Service Plan (IFSP) is developed
during the EI process to identify physical, cognitive,
communication, social-emotional, and adaptive behav-
ior goals. The IFSP should include goals related to the
transition into special education services, usually by
age 3, such as those provided in a special needs
preschool setting. An Individualized Education Plan
(IEP) is developed on entry into special education, and
this details the educational goals and services required
for a free appropriate public education (known as
FAPE). These goals must be reviewed annually by
school authorities, but the primary care clinician can
advocate for revision of the goals on an as-needed
basis to ensure that a child continues to progress.
Another important component of the IEP process is
an assessment of a childs cognitive, language, mem-
ory, visual-motor integration, adaptive behavior, so-
cial-emotional, motor, and academic skills. Triennial
interdisciplinary evaluations through the school are
mandated for children served by IEPs. A clinician may
choose to make a referral for comprehensive testing
with a psychologist familiar with developmental dis-
abilities if, in the clinicians opinion, the schools
evaluation is inadequate. A thorough assessment
should include the areas known to be problematic for
individuals with Down syndrome, including cognition,
language, and memory. For example, the Stanford
Binet Tests of IntelligenceFifth Edition73 is very
helpful in evaluating children with developmental
disabilities as young as 2 years of age as it does not
have timed tasks and it provides a comparison of
verbal versus nonverbal skills, including short-term
(ie, working) memory.59
The following discussion includes strategies that
may be helpful to parents and educators alike. These
strategies may be incorporated into a childs IEP.
While these strategies may be helpful, it is essential
that an individualized educational approach be taken
for each child with Down syndrome, because each
child has a unique profile of skills.
Language improvement strategies should begin as
early as possible and continue into adolescence and
young adulthood.54 Kumin emphasized that improving
speech development and intelligibility should begin as
early as possible (eg, via oral-motor therapy that can
begin during infant feeding treatments) to help lay the
foundation for developing sound templates in the brain
that will enable children to program and sequence
sounds.55 Silverman suggested that children with
Down syndrome may benefit from the intense lan-
255
guage acquisition programs used for children with
autism.50 Teaching individuals with Down syndrome
how to use sign language may encourage language
acquisition and sometimes decrease behavior prob-
lems associated with frustration related to communi-
cation difficulties.52 Interventions should also address
adequately the more advanced receptive language
abilities demonstrated by many individuals with Down
syndrome by having goals such as increasing automa-
ticity of verbal expression via practice, increased wait
time, and prior priming of word forms and content.54
Verbal instructions should be concise, and individuals
with Down syndrome may benefit from progressing
quickly to a hands-on learning approach rather than
one that uses lengthy verbal explanations.52
Finally, some general education strategies can help
increase the success of individuals with Down syn-
drome in educational environments. An educational
strategy often applicable to children with Down syn-
drome is inclusion, which involves spending at least a
portion of the academic day in a mainstream class-
room. There are pros and cons to inclusion, all of
which must be considered regarding the potential
benefits and implications of mainstreaming a child
with Down syndrome. An indirect approach, such as
positioning children with and without disabilities
to play nearby one another, does not lead to increased
peer interaction. However, direct approaches such as
prompting and reinforcing peer interaction as well as
interpreting the behavior of the child with a disability
for the typical child will lead to increased interaction.
Pairing the child with Down syndrome with a peer
buddy may also be helpful.74 Buckley and coworkers
found that mainstreamed adolescents with Down syn-
drome showed significantly better expressive language
and literacy skills than their counterparts who were not
mainstreamed.75 Also, the mainstreamed adolescents
had fewer behavioral difficulties. In addition, children
with Down syndrome often demonstrate avoidance
behavior that may involve refusal to complete tasks
perceived as difficult and/or social ploys used to
distract instructors attention away from the task.76
These behaviors must be monitored and addressed
when present.
Behavioral Interventions
Given the need for medical interventions, child
health clinicians and other medical specialists are
frequently involved in the care of children with Down
syndrome, and health professionals have a pivotal role
256
in making appropriate referrals to behavior health
specialists. Of course, it is important to intervene as
early as possible to prevent or reduce the negative
impact that problematic behaviors have on learning
opportunities for children with Down syndrome.77,78
For example, behavior problems are one of the main
reasons children with Down syndrome are excluded
from general education classrooms.77 Consultation
with a child psychologist or other mental health
professional regarding an overall behavioral support
plan is encouraged.
Complementary and Alternative Medicine
There is no specific medical treatment for the under-
lying cause of Down syndromeall treatments are
aimed at the specific medical complication present in
the patient. Complementary and Alternative Medicine
(CAM) therapies are often employed for children with
Down syndrome in an attempt to improve overall
functioning. Some studies report that more than 85%
of families try at least one type of CAM.79,80 CAM is
generally defined as products or practices not currently
considered part of conventional medicine.81 The types
of CAM typically used for Down syndrome include
vitamins, supplements, and cell therapy as described
below.
A gene on chromosome 21 codes for superoxide
dismutase (SOD), a key enzyme in the breakdown of
free radicals. Oxidative stress (the imbalance between
production of free radicals and removal by antioxi-
dants) has been theorized to play a role in the cogni-
tive, immune, malignancy, and premature aging issues
associated with Down syndrome. Thus, antioxidants
hold some theoretical promise.80 Minerals such as zinc
and selenium have been proposed to play a role in
antioxidation, but definitive research has not been
done.
A small number of dietary supplements trials have
not been found to improve cognition in individuals
with Down syndrome.82 Vitamins A, B6, and thiamin
and niacin are among the CAM treatments studied.
Cell therapy has been more popular in Europe. Sicca
cell therapy consists of subcutaneous injection of
freeze-dried or lyophilized fetal sheep or rabbit brain
cells. Although this type of therapy is not legal in the
United States, some families have traveled to Europe
to obtain it or received it via mail. Allergic, hypersen-
sitivity reactions as well as viral infections are possible
side effects. Preliminary research thus far has not
shown any effect.83
Curr Probl Pediatr Adolesc Health Care, September 2008
 Since greater than 75% of adults over 60 years of age
with Down syndrome have symptoms of Alzheimers
disease,9 medications used to treat Alzheimers have
been tried in patients with Down syndrome. Piracetam
is a medication approved by the FDA for the treatment
of Alzheimers disease. While there have been anec-
dotal reports of improved cognitive functioning, one
small crossover study of piracetam in persons with
Down syndrome failed to show a response. Side
effects included central nervous system stimulatory
effects such as aggression, poor sleep, and decreased
appetite.84 Larger randomized controlled trials are
underway. Other Alzheimers drugs, such as rivastig-
mine, have also been tried in Down syndrome, al-
though there have not been randomized clinical trials
and only a few case reports that involve children.80,85
Of course, families do not always report that they
are using CAM to their childs clinician. Families
report various reasons for this lack of communica-
tion including a sense of disapproval, lack of
provider knowledge, and lack of time.79 Some
families view CAM therapy as a form of advocacy;
they believe it is one more way they can improve
their childs life. For others, it is something positive
they can do for their child, in contrast to the
negative predictions they are accustomed to hearing
from medical and lay sources.86
Since many families are using CAM but not inform-
ing their childs clinician, it is important to inquire
about CAM use in a nonjudgmental manner. Most
parents report being interested in their physicians
opinion, even if it is different from their own. They
would also like more guidance about CAM and
usually accept the fact that their physician may not
have the answers immediately available.79
In summary, CAM represents an area of unmet need
for families, who generally want to be able to discuss
these treatments with their childs clinician. These
discussions would help ensure safe practices and also
address unrealistic expectations and unfounded scien-
tific claims.
Transition
Transition to adult services, including health care,
can be difficult for adolescents with Down syndrome
and their families. As is the case for many children
with special health care needs, adult medical providers
may not be familiar with many important issues for
Curr Probl Pediatr Adolesc Health Care, September 2008
these individuals and families. Among adolescents and
young adults with Down syndrome, this may include
congenital heart defects, GI malformations, and appro-
priate ongoing Down syndrome screening. Multiple
pediatric subspecialty providers, such as ear, nose, and
throat, cardiology, GI, developmental pediatrics, etc,
may be involved, and their adult counterparts are
probably less familiar and comfortable with the care of
individuals with Down syndrome as well as other
adults with disabilities.
Lack of basic health knowledge is another concern
for many adolescents with Down syndrome.87 The
clinician should take advantage of opportunities dur-
ing health supervision and other visits with youngsters
with Down syndrome to explain concepts in develop-
mentally appropriate terms and to encourage appropri-
ate gradual independence in managing health care
needs. This is a process that involves repetition but
may help decrease the risk of later poor health status,
which is unfortunately common among adults with
intellectual disability88 and even more so for adults
with Down syndrome.89 This approach to health liter-
acy is a part of the transition process that should be
addressed at all visits with the primary care provider.
In addition, adolescents with Down syndrome and
their families face tough choices regarding life after
school. Although able to continue in school until age
21, adolescents with Down syndrome may find fewer
inclusive educational settings and fewer social oppor-
tunities as their school careers wind down.90
Families also confront difficult decisions regarding
living arrangements including staying at home, inde-
pendent living situations, and group homes. Within the
medical home, the clinician should counsel families to
prepare for these eventualities early, even if unsure
about future preferences, since there can be very long
waits for some types of placements.
Families also need to consider guardianship and
financial options. Once he/she turns 18, the adoles-
cent with Down syndrome may apply for Social
Security without parental income being a factor.
Consultation with a lawyer or social worker familiar
with disabilities may be helpful. Other family con-
cerns include establishment of trusts, estate execu-
tors, and potential guardians of the child in the event
of the parents unexpected early death.
There are also decisions to be made regarding
vocational options. The possible alternatives include
independent, competitive work; supported employ-
ment; or sheltered workshop employment. The adoles-
257
cent should be involved in the IEP process starting at
age 14, and transition to work planning should be part
of the IEP process starting at age 16.
Overall, this can be a difficult time for adolescents
and their families. The adolescents typically develop-
ing peers may be graduating and moving into the
workforce or college while the adolescent with Down
syndrome remains in high school or transitions to
another setting that continues to require ongoing
parental involvement and supervision. Parents may go
through a period of grieving as they realize anew their
adolescents limitations. It also may be a time when
parents face unresolved behavioral issues or skill
deficits that may negatively impact vocational and
living options.
In addition to providing ongoing medical care during
adolescence, the medical home can assist families with
finding adult medical care, supplying adult providers
with information specific to the individual and about
Down syndrome in general, and advocating along with
families for appropriate adult services and opportuni-
ties. Support from the adolescents medical home can
make this process easier for all involved.
New Research on Chromosome 21
While Down syndrome is a disorder that was iden-
tified more than a century ago, recent research efforts
have led to a more sophisticated understanding of the
genetics of chromosome 21. Chromosome 21 is the
smallest of the 23 human autosomes. In 2000, se-
quencing of the long (q) arm of chromosome 21
estimated that it contains around 225 genes.91 Com-
pared with chromosome 22, chromosome 21 is rela-
tively gene poor, and this may help to explain the
increased viability of fetuses with trisomy 21 com-
pared with other trisomies.10 Phenotype correlations
have been possible from individuals who have
unique translocations that include portions of chro-
mosome 21.5 The idea of a critical region has
been proposed, suggesting that a certain region of
chromosome 21 is responsible for particular clinical
features seen in Down syndrome.92 Other research
has focused on the creation of mouse models that
has enabled additional genetic studies.
As a result of these research efforts, specific genes
on chromosome 21 have been identified, and some of
these genes may hold promise for understanding
certain phenotypic changes seen in Down syndrome.5
258
Two such genes that may be important in the central
nervous system are superoxide dismutase (SOD1) and
amyloid precursor protein. SOD1 is involved in free
radical metabolism and has been suggested to play a
role in the advanced aging process seen in some
individuals with Down syndrome.9 Also located on
chromosome 21, amyloid precursor protein is known
to be involved in neurodegenerative disorders, includ-
ing some cases of Alzheimers disease.93 These and
similar genes may further our understanding of disor-
ders seen with increased frequency in individuals with
Down syndrome.
Despite recent advances, many of the genetic aspects
of Down syndrome remain unclear. For example, not
all of the gene transcripts from chromosome 21 are
expressed at levels of 1.5 times normal, as would be
expected with an extra copy of a chromosome.92
Certain features, such as cognitive impairment,
seem to be present in the majority of individuals,
whereas some abnormalities, such as heart disease
and duodenal atresia, occur with much less fre-
quency. Future research should be directed toward a
better understanding of the role that certain genes
and gene transcripts play in the development of
specific clinical features. This type of research
should enable the development of therapies target-
ing certain medical and psychological abnormalities
associated with trisomy 21.
Summary
Down syndrome is a chromosomal disorder caused
by triplicate material from chromosome 21. It has a
variable phenotypic expression, with a characteristic
constellation of physical findings including distinctive
facial features and anomalies of multiple organ sys-
tems. Advances in genetics have increased our early
detection of the condition, our understanding of its
causes, and potential treatments for its complications.
Provision of a comprehensive medical home and
advocacy for appropriate educational programming
can assure optimal outcomes for children with this
condition.
Acknowledgments. We are grateful to Debra Dun-
lope, RN, Changing Lives Project Manager for the
Down Syndrome Association of Central Ohio, and
Carrie Blout, MS, Certified Genetic Counselor at
Nationwide Childrens Hospital, Columbus, OH for
Curr Probl Pediatr Adolesc Health Care, September 2008
expertise and to J. Lynne Henkel for assistance in
preparing this manuscript.
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