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Down syndrome: Clinical features and

diagnosis
Author: Kathryn K Ostermaier, MD, FAAP
Section Editors: Jan E Drutz, MD, Helen V Firth, DM, FRCP, DCH
Deputy Editor: Elizabeth TePas, MD, MS

All topics are updated as new evidence becomes available and our peer review process is
complete.

Literature review current through: Jun 2020. | This topic last updated: Mar 18, 2019.

INTRODUCTION

Down syndrome (DS) is the most common chromosome abnormality among

liveborn infants. It is the most frequent form of intellectual disability caused by
a microscopically demonstrable chromosomal aberration. DS is characterized
by a variety of dysmorphic features, congenital malformations, and other
health problems and medical conditions. Not all of them are present in each
affected individual. The impact of DS for each person is individual, with some
individuals being profoundly impacted while others are healthy and able to live
independently as adults. In general, individuals with DS are now reaching
fuller potentials secondary to better educational programs, medical
advancements, community resources, and the support of family and friends.

The clinical features and diagnosis of DS will be presented here. The

epidemiology, genetics, and management are discussed separately. (See
"Down syndrome: Overview of prenatal screening" and "Congenital
cytogenetic abnormalities", section on 'Trisomy 21 (Down syndrome)' and
"Down syndrome: Management".)

DYSMORPHIC FEATURES

Upslanting palpebral fissures, epicanthic folds, and brachycephaly are nearly

universal features of DS. The other characteristic dysmorphic features of DS
are each present in 47 to 82 percent of cases [1,2]. These features
predominantly affect the head and neck and the extremities.

Head and neck — Characteristic dysmorphic features of DS affecting the

head and neck include:

● Upslanting palpebral fissures

● Epicanthic folds (picture 1)
● Flat facial profile/flat nasal bridge
● Folded or dysplastic ears
● Low-set small ears
● Brachycephaly
● Brushfield spots
● Open mouth
● Protruding tongue (picture 1)
● Furrowed tongue
● Short neck
● Excessive skin at nape of the neck
● Narrow palate
● Abnormal teeth

Extremities — Characteristic dysmorphic features of DS affecting the

extremities include:

● Short broad hands

 ● Incurved fifth finger with hypoplastic mid phalanx
● Transverse palmar crease (picture 2)
● Space between the first and second toes (sandal gap)
● Hyperflexibility of joints

Neonatal features — Ten of the characteristic dysmorphic features are

common in newborns with DS and are usually recognized soon after birth. In
a series of 48 affected newborns, all had four or more features, and 89
percent had six or more [1,3]:

● Flat facial profile

● Slanted palpebral fissures
● Anomalous ears
● Hypotonia (picture 3)
● Poor Moro reflex
● Dysplasia of midphalanx of fifth finger
● Transverse palmar (Simian) crease (picture 2)
● Excessive skin at nape of the neck
● Hyperflexibility of joints
● Dysplasia of pelvis

INTELLECTUAL DISABILITY

Almost all individuals with DS have cognitive impairment, although the range
is wide. Most are mildly to moderately intellectually disabled, with an
intelligence quotient (IQ) in the 50 to 70 or 35 to 50 range, respectively,
although some are severely impaired with an IQ of 20 to 35 [4]. (See
"Intellectual disability in children: Definition, diagnosis, and assessment of
needs".)

Developmental impairment becomes apparent in the first year of life. In

general, the average age of sitting (11 months), creeping (17 months), and
walking (26 months) is approximately twice the typical age [5]. The sequence
of language development is the same, although the rate is slower, with the
average age for the first word at 18 months [6]. The child with DS continues to
learn new skills. However, IQ declines through the first 10 years of age,
reaching a plateau in adolescence that continues into adulthood [2,7,8]. (See
"Developmental-behavioral surveillance and screening in primary care",
section on 'Approach to surveillance'.)

The profile of cognitive impairment in DS appears to differ from other forms of

intellectual disability. The cognitive deficits are primarily in morphosyntax,
verbal short-term memory, and explicit long-term memory [9]. The most
common profile, in which language comprehension is equal to mental age and
language production is more delayed, occurs in two-thirds of affected children
[10]. In one-third, language comprehension, mental age, and language
production are equal. Impairment in expressive language was noted in
another study of children with DS, who had fewer different and total words
and decreased mean length of utterance compared with controls matched for
nonverbal mental age [11]. Vocabulary skills accelerated more rapidly than
syntax (average sentence length and structure) and surpassed mental age in
adolescence. Similar findings of increasing differences in comprehension with
age were noted in another report, in which children with DS developed
relatively stronger skills in vocabulary compared with syntax [12]. Other
selective deficits have been described, such as greater difficulty
understanding sequences or grammatical rules [2,13].

Behavioral and psychiatric disorders — Behavioral and psychiatric

disorders are more common in DS than typical children but less common than
in those with other causes of intellectual disability [8]. In one report,
psychiatric disorders affected 17.6 percent of individuals with DS less than 20
years of age [14]. Disruptive behavioral disorders, such as attention-deficit
hyperactivity disorder, conduct/oppositional disorder, or aggressive behavior,
were most common. In the same study, psychiatric disorders, most often
consisting of major depressive illness or aggressive behavior, affected 25.6
percent of DS adults. (See "Attention deficit hyperactivity disorder in children
and adolescents: Clinical features and diagnosis", section on 'Clinical
features' and "Attention deficit hyperactivity disorder in adults: Epidemiology,
pathogenesis, clinical features, course, assessment, and diagnosis" and
"Unipolar depression in adults: Assessment and diagnosis" and "Pediatric
unipolar depression: Epidemiology, clinical features, assessment, and
diagnosis".)

Autism is a common comorbidity of DS, affecting as many as 7 percent of

children with DS [15]. The diagnosis is often delayed compared with children
without DS [16]. Some children with DS present in the school-aged years with
new-onset or worsening autistic-like features, cognitive decline to the point of
dementia, and new-onset insomnia [17]. The term "Down syndrome
disintegrative disorder" has been suggested to describe this cluster of clinical
findings, although it is not clear if this is one disorder or several different ones
with similar presentations. The etiology is not known, but autoimmunity is
suspected. There are no established diagnosis or treatment
recommendations for this clinical association. Some patients respond to
psychiatric care. Further research is needed in this area. (See "Autism
spectrum disorder: Clinical features".)

Dementia/Alzheimer disease — Adults with DS usually develop

neuropathologic and functional changes typical of Alzheimer disease by the
sixth decade of life [8,18,19]. In one report, dementia was present in 49 of 96
(51 percent) DS individuals over the age of 35 years [18]. The average age of
onset was 54 years, and seizures developed in 84 percent of patients. In
another report, over 75 percent of patients over 65 years of age were affected
[9]. (See "Evaluation of cognitive impairment and dementia".)

CARDIOVASCULAR DISEASE
Approximately one-half of individuals with DS have congenital heart disease
[20-22]. In the largest population-based study, cardiovascular abnormalities
were identified in 342 of 821 (42 percent) infants born with DS from 1985 to
2006 in the northeast region of England [22]. Twenty-three percent had more
than one anomaly. The secondary lesion was most commonly an atrial septal
defect (ASD) or patent ductus arteriosus (PDA). The following primary lesions
were identified:

● Complete atrioventricular septal defect (CAVSD) – 37 percent

● Ventricular septal defect (VSD) – 31 percent
● ASD – 15 percent
● Partial atrioventricular septal defect (PAVSD) – 6 percent
● Tetralogy of Fallot (TOF) – 5 percent
● PDA – 4 percent
● Miscellaneous – 2 percent

The clinical features of these defects are discussed separately. (See "Isolated
atrial septal defects (ASDs) in children: Classification, clinical features, and
diagnosis" and "Isolated ventricular septal defects in infants and children:
Anatomy, clinical features, and diagnosis" and "Clinical manifestations and
diagnosis of patent ductus arteriosus in term infants, children, and adults" and
"Pathophysiology, clinical features, and diagnosis of tetralogy of Fallot".)

Some asymptomatic adolescents and adults without structural heart disease

develop valve abnormalities [23,24]. In a series of 35 patients with DS, mitral
valve prolapse occurred in 46 percent and aortic regurgitation in 6 percent at
an average age of 20 years [23]. In another report of 30 adults, mitral valve
regurgitation occurred in 17 percent [24].

Pulmonary hypertension is also common, occurring in 28 percent of patients

with DS in one retrospective review [25]. The median age at diagnosis was
five days in this review, with the majority (70 percent) having transient disease
that lasted a median of eight months. Recurrent disease occurred in 15
percent and was associated with congenital heart disease, obstructive sleep
apnea, recurrent pneumonia, and intermittent hypoxia. The remaining 15
percent had persistent disease. (See 'Pulmonary disorders' below.)

GASTROINTESTINAL ABNORMALITIES

Children with trisomy 21 are at increased risk for gastrointestinal tract

anomalies, which occur in approximately 5 percent of cases [26]. Duodenal
atresia or stenosis, sometimes associated with annular pancreas, is the most
characteristic lesion, occurring in 2.5 percent [2]. Imperforate anus and
esophageal atresia with tracheoesophageal fistula are seen less often.
Conversely, DS affects 28 percent of patients with duodenal atresia or
stenosis and 20 percent with annular pancreas. (See "Intestinal atresia" and
"Annular pancreas" and "Prenatal diagnosis of esophageal, gastrointestinal,
and anorectal atresia" and "Congenital anomalies of the intrathoracic airways
and tracheoesophageal fistula", section on 'Tracheoesophageal fistula and
esophageal atresia'.)

Hirschsprung disease is more common in DS than in the general population,

although the risk is less than 1 percent [4]. Among children with Hirschsprung
disease, approximately 2 percent have trisomy 21 (with a range of 2 to 15
percent) [27-31]. (See "Congenital aganglionic megacolon (Hirschsprung
disease)".)

A strong association appears to exist between DS and celiac disease. The

prevalence of biopsy-proven celiac disease has been reported to be between
5 and 16 percent, representing a 5- to 16-fold increase compared with the
general population [32-36]. (See "Epidemiology, pathogenesis, and clinical
manifestations of celiac disease in children", section on 'Down syndrome'.)

GROWTH
Birth weight, length, and head circumference are less in DS compared with
typical infants. Newborns with DS weigh approximately 0.18 to 0.37 kg less
than their siblings [37]. Mean length at birth is approximately 0.5 standard
deviations less than control newborns [38]. In a study of 105 children with DS,
growth parameters remained lower until puberty, with the growth spurt being
earlier (age 11 in boys and 9.5 in girls), and were blunted compared with
controls [39]. Weight gain during the first three years of life has improved
since the 1980s, as has stature in males [40-42].

Short stature — Growth rate is reduced in DS compared with typical

children, especially in infancy and adolescence. Growth is most reduced in
children with severe congenital heart disease [38,40]. In adults with DS, the
average height in males and females was 61.7 and 57 inches (157 and 144
cm), respectively, and the average weight was 157 and 140 lb (71 and 64 kg)
in males and females in a 1998 study [43]. Measurement of growth in patients
with DS is discussed separately. (See "Down syndrome: Management",
section on 'Growth'.)

The cause of DS-associated growth retardation remains unknown. Low

circulating levels of insulin-like growth factor 1 (IGF-1) and diminished
provoked and spontaneous secretion of growth hormone (GH) have been
reported in some patients [44,45]. Serum GH levels are not low in children
with DS [46,47], but suboptimal endogenous GH production as a result of
hypothalamic dysfunction has been demonstrated [48]. Selective deficiency of
IGF-1, but not IGF-2, has been seen in DS patients who are older than two
years [49,50]. IGF-1 receptors are present in brain cells from fetuses with
trisomy 21 [50].

Obesity — The prevalence of obesity (defined as a body mass index [BMI]

>27.8 kg/m2 in adult males and >27.3 kg/m2 in adult females) is greater in DS
than in the general population (45 versus 33 percent, 56 versus 36 percent,
for males and females, respectively) [43]. This is thought to result from the
reduced resting metabolic rate in children and adults with DS [51,52]. In
general, weight is less than expected for length in infants with DS and then
increases disproportionally so that the majority of children are obese by age
three to four years [8]. (See "Down syndrome: Management", section on
'Obesity prevention'.)

EYE PROBLEMS

Ophthalmologic disorders that require monitoring and intervention affect the

majority of children with DS. Disorders that are the most common include
[8,53-57]:

● Refractive errors (myopia, hyperopia, astigmatism) – 35 to 76 percent

● Strabismus – 25 to 57 percent
● Nystagmus – 18 to 22 percent

Cataracts occur in 5 percent of newborns. Starting in the second decade of

life, many individuals develop corneal opacities. Children occasionally
develop glaucoma. (See "Overview of glaucoma in infants and children" and
"Cataract in children", section on 'Clinical features'.)

The frequency of ocular disorders increases with age. In one report, eye
abnormalities occurred in 38 percent of infants 2 to 12 months of age and 80
percent of children age 5 to 12 years [53]. These abnormalities may be more
prevalent in adults. In one report of 30 institutionalized adults with DS, only
one had nearly normal ocular status [58]. Nine had keratoconus, an abnormal
shape or thinning of the cornea that impairs visual acuity.

HEARING LOSS

Hearing impairment affects 38 to 78 percent of individuals with DS [8,59,60].

Otitis media is a frequent problem, affecting 50 to 70 percent of DS children,
and it is often the cause of hearing loss in this population [4]. Monitoring for
this condition is important to preserve hearing. Congenital hearing loss is also
more common in DS, identified in 15 percent of newborns with DS compared
with 0.25 percent in the total neonate population in one retrospective review
[61].

The characteristics of hearing loss were illustrated by a study of 47 children

with DS, 2 months to 3.5 years of age, evaluated by auditory brainstem
response testing [60]. The following findings were noted:

● The loss was unilateral or bilateral in 28 and 38 percent, respectively; 34

percent of patients had normal hearing.
● The loss was conductive in 19 ears, sensorineural in 16, and mixed in 14.
● The extent of loss was mild, moderate, and severe to profound in 33, 13,
and 3 ears, respectively.

Another series of 332 children with DS born in Utah found that [62]:

● Forty-six percent had hearing loss, 32 percent of whom were identified on

newborn screening and the rest in later infancy.

● Most newborns and infants had conductive hearing loss due to serous
otitis media and required placement of tympanostomy tubes, although a
few children were identified with sensorineural or mixed hearing loss,
primarily identified by newborn screening.

ENDOCRINE DISORDERS

Endocrine abnormalities in DS include thyroid dysfunction and diabetes.

Thyroid disease — Thyroid disorders are common in DS. The prevalence

varies, depending in part upon the population studied and the age of testing.
The prevalence of hypothyroidism ranged from 3 to 54 percent in reports of
adults with DS [63]. Hyperthyroidism is also relatively common, occurring in
2.5 percent of institutionalized adults [64].
Thyroid disease is also frequently seen in children with DS, as indicated in the
following reports:

● In a longitudinal study of 85 DS patients up to 25 years of age, 35

percent had hypothyroidism. One-half developed the disorder before age
eight years [63]. Two percent had hyperthyroidism.

● In 320 children with DS aged five days to 10 years, 28 percent had

abnormal thyroid function tests [65]. Of these, diagnoses included
primary congenital hypothyroidism in 6, acquired hypothyroidism in 1,
transient hyperthyrotropinemia in 2, compensated hypothyroidism (T4
concentration normal or close to the lower limit of normal and increased
thyroid-stimulating hormone [TSH] level) in 16, and mild compensated
hypothyroidism (mildly elevated TSH concentration) in 65. None had
hyperthyroidism.

● In a retrospective cohort study of 122 infants <4 months of age with DS,
17.5 percent had primary hypothyroidism that required therapy, and 15
percent had compensated hypothyroidism [66].

However, there is a shift in thyroid hormone levels in patients with DS who

have no overt symptoms of thyroid disease, suggesting that normal values
may be different in this group. In a large cohort from a neonatal screening
program, T4 concentrations in newborns with DS had a normal distribution but
were shifted to lower concentrations than the general population [67]. Mean
TSH concentration was significantly increased (9.76 versus 3.96 milli-
international units/L), and T4-binding globulin was normal compared with
controls. The distribution plots for TSH and free T4 were shifted to higher
values in another study of patients with DS (median age 10, range six months
to 64 years) [68].

Diabetes — The risk of type 1 diabetes appears to be increased in DS

[36,69-71]. Data from a Dutch study in children up to 14 years of age suggest
the risk of type 1 diabetes is three times greater in DS than in the general
population (50 versus 12.4 per 100,000 per year) [70,71]. In another study,
the estimated prevalence of type 1 diabetes in DS children up to nine years of
age was eight times greater than the age-matched control population (335
versus 40 per 100,000) [70].

HEMATOLOGIC DISORDERS

Hematologic abnormalities affecting red blood cells, white blood cells, and
platelets are common in DS, particularly during childhood. The lifetime risk of
leukemia in DS is 1 to 1.5 percent [72,73].

Approximately 65 percent of newborns with trisomy 21 have polycythemia

[74]. In one report, plasma erythropoietin concentration measured in umbilical
cord blood was higher in infants with DS compared with controls, suggesting
that chronic fetal hypoxemia may explain the high incidence of polycythemia
[75]. (See "Neonatal polycythemia".)

Children with DS often have macrocytosis [74,76]. In one study, mean

corpuscular volume (MCV) was greater in DS children age two to six years
compared with controls (86.9 versus 80.6 fL), and MCV >95th percentile for
age was more likely to occur (66 versus 11 percent) [76]. Hematocrits were
higher in the DS patients (39.1 versus 36.9 percent), although all were normal
for age. (See "Macrocytosis/Macrocytic anemia".)

White blood cell counts are decreased in DS [74,76]. In the study cited above,
white blood cell counts <5th percentile for age occurred more often in DS than
controls (33 versus 6 percent) [76]. The macrocytosis and leukopenia were
not explained by folate deficiency, because serum and red blood cell folate
concentrations were similar between the patients and controls.
Thrombocytosis is common in infancy, and thrombocytopenia is rare [74].

Transient myeloproliferative disorder — Transient myeloproliferative

disorder (TMD), also known as transient leukemia or transient abnormal
myelopoiesis (TAM), is a form of leukemia that almost exclusively affects
newborns with DS. It is typically detected on routine screening with a
complete blood count (identification of blasts on the peripheral smear). The
majority of newborns are asymptomatic, with spontaneous resolution of the
disorder by two to three months (median 54 days), although some develop
severe disease including hydrops fetalis, hyperleukocytosis, liver failure, and
cardiopulmonary failure. TMD is discussed in greater detail separately. (See
"Transient myeloproliferative disorder of Down syndrome".)

Acute megakaryoblastic leukemia — In prospective and retrospective

studies, up to 26 percent of infants with transient leukemia later developed the
French-American-British (FAB) classification system M7 subtype of acute
myeloid leukemia (AML-M7), also known as acute megakaryoblastic leukemia
(AMKL) or myeloid leukemia of DS (ML-DS) [77-79]. AMKL occurs in
approximately 1 in 50 to 200 children with DS. The incidence is approximately
500 times greater in children with than without DS. (See "Classification of
acute myeloid leukemia".)

AMKL develops during the first four years of life. It is most commonly seen by
two years of age and is invariably associated with mutations in guanine-
adenine-thymine-adenine (GATA)-binding factor 1 gene (GATA1) [73,78,80-
85]. In contrast, myeloid leukemias in people with DS aged four years or older
are usually negative for GATA1 mutations, and their prognosis does not differ
from AML in patients without DS. Many affected patients (20 to 69 percent)
present with myelodysplastic syndrome, consisting of progressive
thrombocytopenia followed by anemia [72]. Some develop hepatomegaly and
liver failure due to fibrosis [86]. Neutropenia and infection rarely are seen [86].
Treatment issues are complex as children with DS and either acute
lymphoblastic leukemia (ALL) or AMKL are subject to high initial rates of
treatment-related mortality [87]. (See "Overview of the outcome of acute
lymphoblastic leukemia/lymphoma in children and adolescents", section on
'Down syndrome'.)
There is evidence that these GATA1 mutations are acquired in utero and that
finding such mutations at birth might serve as a biomarker for an increased
risk of transient leukemia and subsequent AMKL [88,89]. In one study, three
of four children with DS and AMKL had the same GATA1 mutation in a
neonatal blood spot (Guthrie card) that was found at the time of clinical
diagnosis of AMKL 12 to 26 months later [90].

Gene expression profiling may help in distinguishing transient leukemia from

AMKL [91] and identifying those at risk of progressing from transient leukemia
to AMKL [92], as well as distinguishing the AMKL seen in children with DS
from AMKL seen in those without DS [93].

Acute lymphoblastic leukemia — The risk of developing ALL is

approximately 10 to 20 times higher in DS compared with children without DS
[36,94-96] and accounts for 1 to 3 percent of all patients with ALL. The clinical
presentation is similar to that in children without DS. (See "Overview of the
clinical presentation and diagnosis of acute lymphoblastic
leukemia/lymphoma in children".)

In a report comparing ALL in children with and without DS, the following
findings were noted at presentation [72,94]:

● Leukocyte count and leukemic cell mass were similar.

● Age distribution and immunophenotype were similar.

● Clinically, they were indistinguishable [73].

● Mediastinal mass (1.6 versus 8.9 percent) and central nervous system
(CNS) leukemia (0 versus 2.7 percent) were less common in DS, both
favorable prognostic signs.

● Less T cell leukemia or translocation of (9;22) or t(4;11) were seen in DS,

both unfavorable prognostic signs.
 ● Cytogenetic differences occurred, including less hyperdiploidy in DS, an
unfavorable prognostic sign.

Children with DS who develop ALL often respond to chemotherapy, similar to

children without DS. The treatment and outcome for children with DS and ALL
are discussed separately. (See "Overview of the outcome of acute
lymphoblastic leukemia/lymphoma in children and adolescents", section on
'Down syndrome'.)

PULMONARY DISORDERS

Sixty percent of 208 children with DS in a 2004 survey were reported by their
parents to have respiratory conditions, including sleep apnea and asthma
[97], although this may be an underestimate based upon results from other
studies [98]. Other pulmonary complications that are more common in
children with DS include disorders of the pulmonary vasculature, parenchymal
lung disease, upper and lower airway abnormalities, and chronic aspiration
[99]. Respiratory tract infections are also more frequent and often more
severe than in children without DS.

Sleep apnea — Obstructive sleep apnea (OSA) occurs in at least 30 to 75

percent of children with DS, including those who are not obese [98,100-106].
In a population of 65 unselected 3.5 year olds with DS, polysomnograms were
classified as abnormal with evidence of OSA in 57 percent. Among the 45
children whose parents reported no sleep problems, 54 percent had abnormal
results [98]. The mechanism includes soft tissue and skeletal alterations that
lead to upper airway obstruction. In infants with DS, OSA was associated with
dysphagia, gastrointestinal conditions such as gastroesophageal reflux
disease, and congenital heart disease [106]. Intermittent hypoxemia may lead
to pulmonary hypertension and contribute to mental impairment [107]. (See
"Mechanisms and predisposing factors for sleep-related breathing disorders in
children".)
SKIN DISORDERS

The majority of DS children have associated skin disorders, which are

considered benign [108-110]. In one series, 62 of 71 children (87 percent) had
skin abnormalities in the following proportions [111]:

● Palmoplantar hyperkeratosis – 41 percent

● Seborrheic dermatitis – 31 percent
● Fissured tongue – 20 percent
● Cutis marmorata – 13 percent
● Geographic tongue – 11 percent
● Xerosis – 10 percent
● Alopecia areata – 8 percent [108,109]

In adolescents, dermatologic problems become particularly bothersome. The

most common condition in this age group is folliculitis, which affects 50 to 60
percent of patients [112].

REPRODUCTION

Women with DS are fertile and may become pregnant. In one series, 30
pregnancies in 26 women resulted in 10 offspring with DS, 18 (including one
set of twins) without DS, and 3 spontaneous abortions [113]. Appropriate
counseling should be provided for management of menstruation and
contraception [114].

Nearly all males with DS are infertile. The mechanism is impairment of

spermatogenesis [115]. However, cases have been reported of offspring from
fathers with DS [116,117].

UROLOGIC ABNORMALITIES
Studies suggest an increased incidence of urologic abnormalities in
individuals with DS. These include hypospadias (1 in 250 males),
cryptorchidism (14 to 27 percent of males), testicular cancer, and renal
malformations (3.5 percent) [118]. (See "Hypospadias: Pathogenesis,
diagnosis, and evaluation" and "Undescended testes (cryptorchidism) in
children: Clinical features and evaluation" and "Clinical manifestations,
diagnosis, and staging of testicular germ cell tumors" and "Overview of
congenital anomalies of the kidney and urinary tract (CAKUT)".)

ATLANTOAXIAL INSTABILITY

Atlantoaxial instability (AAI), defined as excessive mobility of the articulation

of the atlas (C1) and the axis (C2), may lead to subluxation of the cervical
spine [119]. Approximately 13 percent of individuals with DS have
asymptomatic AAI, while spinal cord compression due to the disorder affects
approximately 2 percent [120]. The diagnosis is made by lateral neck
radiographs taken in neutral position, flexion, and extension. (See "Down
syndrome: Management", section on 'Atlantoaxial instability'.)

Patients with symptomatic spinal cord compression may have neck pain,
torticollis, gait abnormalities, loss of bowel or bladder control, or signs of
quadriparesis or quadriplegia and require immediate stabilization.
Asymptomatic individuals appear to remain asymptomatic whether or not
physical activity is restricted [121,122]. In one study, DS children with AAI
were randomly assigned to participate or not in athletic activities considered
to be risky and evaluated after one year. The groups were similar in motor
function, frequency of neurologic signs, and changes in atlantoaxial distance
and were also similar to children with DS and without AAI [121].

ARTHROPATHY
DS arthropathy has a prevalence of 8 to 10 per 1000, or approximately six
times the prevalence of juvenile idiopathic arthritis in the general population
[123]. In a review of 30 cases, 17 had polyarticular disease at symptom onset,
and 13 had oligoarticular disease at symptom onset, but seven of these
progressed to polyarticular disease. Average delay from symptom onset to
diagnosis was two years.

IMMUNODEFICIENCY

DS is associated with a variety of immunologic impairments that are thought

to be related to the increased susceptibility to infection, autoimmune
disorders, and malignancies [124-128]. Chemotactic defects [129], decreased
immunoglobulin G4 (IgG4) levels [130], and quantitative and qualitative
abnormalities of the T cell and B cell systems have been inconsistently
demonstrated [124-126,131]. Whether these represent a primary
immunodeficiency or early senescence of the immune system is uncertain.

Support for an intrinsic immunodeficiency is provided by a cross-sectional

study in which immunophenotyping was used to evaluate lymphocyte
subpopulations in 96 children with DS who ranged in age from 1 to 20 years
[132]. In another study, children with DS had a diminished expansion of T and
B cells in the first years of life compared with previously published data on
healthy children without DS [133]. B cells remained diminished (with 88
percent of values below the 10th percentile), although T cells eventually
approximated normal levels. Reduced naive mature and memory B cell
numbers and evidence of impaired antigen selection for IgM+ and IgA+
memory B cells were seen in one small study [134].

DIAGNOSIS OF DOWN SYNDROME

The diagnosis of DS is often made by prenatal screening. (See "First-
trimester combined test and integrated tests for screening for Down syndrome
and trisomy 18" and "Laboratory issues related to maternal serum screening
for Down syndrome".)

When no prenatal diagnosis is available, DS is usually recognized from the

characteristic phenotypic features present in the newborn (see 'Dysmorphic
features' above). Diagnosis should be confirmed with a genetic test (eg, a
karyotype performed on a blood sample). Alternative methods (eg, interphase
fluorescent in situ hybridization [FISH] for trisomy 21 or quantitative
fluorescence-polymerase chain reaction [QF-PCR]) may be used to expedite
diagnosis, but these investigations should always be followed by a full
karyotype in order to detect DS due to translocations (eg, Robertsonian
translocations involving chromosome 21) or mosaic DS.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected

countries and regions around the world are provided separately. (See "Society
guideline links: Down syndrome".)

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encourage you to print or e-mail these topics to your patients. (You can also
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(Beyond the Basics)")

SUMMARY

● The characteristic dysmorphic features of Down syndrome (DS)

predominantly affect the head and neck and the extremities. Ten of the
characteristic dysmorphic features are common in newborns with DS and
are usually recognized soon after birth. (See 'Dysmorphic features'
above.)

● Almost all individuals with DS have cognitive impairment, although the

range is wide. Most are mildly to moderately intellectually disabled,
although some are severely impaired. Behavioral and psychiatric
disorders are more common in DS than typical children but less common
than in those with other causes of intellectual disability. (See 'Intellectual
disability' above.)

● Approximately one-half of individuals with DS have congenital heart

disease. Septal defects are the most common. Some asymptomatic
adolescents and adults without structural heart disease develop valve
abnormalities. (See 'Cardiovascular disease' above.)
● Children with trisomy 21 are at increased risk for gastrointestinal tract
anomalies, including duodenal atresia or stenosis, imperforate anus, and
esophageal atresia with tracheoesophageal fistula. They are also at
increased risk for celiac disease and Hirschsprung disease. (See
'Gastrointestinal abnormalities' above.)

● Birth weight, length, and head circumference are less in DS compared

with typical infants. The growth rate for height is reduced in DS compared
with typical children. In general, weight is less than expected for length in
infants with DS and then increases disproportionally so that the majority
of children are obese by age three to four years. (See 'Growth' above.)

● Ophthalmologic disorders are common in patients with DS and increase

in frequency with age. These disorders include refractive errors,
strabismus, nystagmus, cataracts, and keratoconus. Hearing loss is also
common, and otitis media is a frequent problem. (See 'Eye problems'
above and 'Hearing loss' above.)

● Endocrine abnormalities in DS include thyroid dysfunction and type 1

diabetes. (See 'Endocrine disorders' above.)

● Hematologic abnormalities affecting red cells, white cells, and platelets

are common in DS and include polycythemia, macrocytosis, leukopenia,
thrombocytosis, and leukemia (transient, acute megakaryoblastic, and
acute lymphoblastic). (See 'Hematologic disorders' above.)

● Women with DS are fertile and may become pregnant. However, nearly
all males with DS are infertile. (See 'Reproduction' above.)

● Increased rates of urologic abnormalities, arthropathy, pulmonary

disease, and benign skin disorders are also seen in patients with DS.
(See 'Urologic abnormalities' above and 'Arthropathy' above and
'Pulmonary disorders' above and 'Skin disorders' above.)
 ● Individuals with DS are at increased risk of atlantoaxial instability (AAI),
defined as excessive mobility of the articulation of the atlas (C1) and the
axis (C2), although spinal cord compression due to subluxation of the
cervical spine is uncommon. (See 'Atlantoaxial instability' above.)

● DS is associated with a variety of immunologic impairments that are

thought to be related to the increased susceptibility to infection,
autoimmune disorders, and malignancies. However, these defects are
inconsistently demonstrated. Whether these represent a primary
immunodeficiency or early senescence of the immune system is
uncertain. (See 'Immunodeficiency' above.)

● The diagnosis of DS is often made by prenatal screening. DS is

otherwise usually recognized from the characteristic phenotypic features
present in the newborn. A clinical diagnosis of DS should be confirmed
by genetic testing whenever possible. (See 'Diagnosis of Down
syndrome' above and "First-trimester combined test and integrated tests
for screening for Down syndrome and trisomy 18" and "Laboratory issues
related to maternal serum screening for Down syndrome" and 'Neonatal
features' above.)

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Topic 2917 Version 29.0

GRAPHICS

Down syndrome facies

Characteristic facial features of Down syndrome depicted in a term (A) and preterm (B) infant include:
epicanthal folds, slanted palpebral fissures, flat nasal bridge, and protruding tongue.

Reproduced with permission from: Clark DA. Atlas of Neonatology, WB Saunders, Philadelphia 2000. Copyright ©
2000 Elsevier.

Graphic 64030 Version 2.0

Transverse palmar crease

Reproduced with permission from: Clark DA. Atlas of Neonatology, WB Saunders, Philadelphia
2000. Copyright © 2000 Elsevier.

Graphic 79414 Version 2.0

Hypotonia: Severe head lag

Reproduced with permission from: Clark DA. Atlas of Neonatology, WB Saunders, Philadelphia
2000. Copyright ©2000 Elsevier.

Graphic 68246 Version 3.0

Contributor Disclosures
Kathryn K Ostermaier, MD, FAAP Nothing to disclose Jan E Drutz, MD Nothing to
disclose Helen V Firth, DM, FRCP, DCH Nothing to disclose Elizabeth TePas, MD,
MS Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group.
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 Official reprint from UpToDate®
www.uptodate.com ©2020 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Down syndrome: Management

Author: Kathryn K Ostermaier, MD, FAAP
Section Editors: Helen V Firth, DM, FRCP, DCH, Jan E Drutz, MD
Deputy Editor: Elizabeth TePas, MD, MS

All topics are updated as new evidence becomes available and our peer review process is
complete.

Literature review current through: Jun 2020. | This topic last updated: Mar 27, 2019.

INTRODUCTION

Down syndrome (DS) is the most common chromosome abnormality

among live-born infants. It is the most frequent form of intellectual disability
caused by a microscopically demonstrable chromosomal aberration.

The Committee on Genetics of the American Academy of Pediatrics (AAP)

has provided recommendations to assist primary care clinicians in the care
of children with DS (table 1) [1]. Management requires an organized
approach to the initial and ongoing evaluation and monitoring for
associated abnormalities and prevention of common disorders [2,3]. Some
patients are also followed by specialists in a Down syndrome clinic, where
they may have additional health care needs related to DS addressed.

The management and life expectancy of children with DS are presented

here. The epidemiology, clinical features, and diagnosis are discussed
separately. (See "Down syndrome: Overview of prenatal screening" and
"Congenital cytogenetic abnormalities", section on 'Trisomy 21 (Down
syndrome)' and "Down syndrome: Clinical features and diagnosis".)

General issues related to management of adults with intellectual disability,

and problems related to DS specifically, are discussed in detail separately.
(See "Primary care of the adult with intellectual and developmental
disabilities".)

GROWTH

Patients with DS should be monitored for disturbances of growth

associated with other disorders, such as hypothyroidism or celiac disease,
and for excessive weight gain.

DS-specific growth charts based upon populations in the United States [4-
6], the United Kingdom and Ireland [7], Italy [8], the Netherlands [9], and
Sweden [10] have been published. The 2015 DS-specific US growth charts
[6], which are consistent with the more contemporary charts based upon
data from European populations [7,10,11], will most likely supplant the
Centers for Disease Control (CDC) and World Health Organization (WHO)
growth charts for assessing growth and nutritional status in children with
DS. The updated 2015 DS-specific growth charts are optimal for
assessment of height, weight, and head circumference and should be
used, if available, rather than the old DS growth charts. The one exception
is the body mass index (BMI) measurement. The 2015 US charts include
weight-for-length and corresponding BMI charts that are needed to
adequately assess nutritional status, although optimal weight-for-length and
BMI levels for individuals with DS are not yet established. In addition, one
study showed that the CDC BMI growth chart using the 85th percentile was
more sensitive for excess adiposity than the new DS-specific BMI chart
[12]. (See "Measurement of growth in children".)

Obesity prevention — A goal of growth monitoring is the prevention of

obesity. Interventions beginning at 24 months of age should include
attention to diet and promotion of physical activity. Caloric intake should be
less than the age-specific recommendations for unaffected individuals [13].
Calcium and vitamin D intake should be monitored closely to minimize
bone loss since adults with DS have lower bone mineral density than
controls [14,15].

CARDIAC DISEASE

All newborns with DS should be evaluated for congenital heart disease in

consultation with a pediatric cardiologist. An echocardiogram is
recommended to detect abnormalities that may not be symptomatic or
apparent on physical examination. Continued clinical cardiac evaluation is
needed because of the high risk of mitral valve prolapse and aortic
regurgitation in adolescents and young adults [2]. In a large, retrospective
cohort study of congenital heart surgery, patients with DS had similar
mortality, but higher morbidity, compared with patients without DS [16].
(See "Identifying newborns with critical congenital heart disease" and
"Isolated atrial septal defects (ASDs) in children: Management and
outcome" and "Management of isolated ventricular septal defects in infants
and children" and "Management of patent ductus arteriosus in term infants,
children, and adults" and "Management and outcome of tetralogy of
Fallot".)

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

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

OPHTHALMOLOGIC DISORDERS

An ophthalmologic assessment should be performed in the newborn period

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

Thyroid function testing (both total thyroxine [tT4] and thyroid-stimulating

hormone [TSH]) should be obtained in the newborn period [17]. The
American Academy of Pediatrics (AAP) recommends that screening should
be repeated at 6 and 12 months and then annually [1]. However, there is
debate regarding the optimal frequency of laboratory screening [18-21].
Height and weight should be measured yearly since the combination of
deceleration of linear growth associated with weight gain is a sensitive
indicator of hypothyroidism [20]. (See "Clinical features and detection of
congenital hypothyroidism".)

CELIAC DISEASE

Screening for symptoms of celiac disease should begin at one year of age
[1]. Laboratory screening is recommended if signs or symptoms develop.
(See "Diagnosis of celiac disease in children".)

HEMATOLOGY

A complete blood count and differential should be obtained at birth to

evaluate for myeloproliferative disorders and polycythemia. Infants with
transient myeloproliferative disorders should be followed with a complete
blood count and differential every three months until three years of age and
then every six months until six years of age. This monitoring protocol is
modified from that used in the prospective study of transient leukemia in
DS conducted by the Pediatric Oncology Group [22]. Children with DS are
at increased risk for leukemia. Thus, there should be vigilance for signs of
leukemia, such as anemia, increased infections, and excessive bruising.
(See "Down syndrome: Clinical features and diagnosis", section on
'Hematologic disorders' and "Neonatal polycythemia" and "Overview of the
clinical presentation and diagnosis of acute lymphoblastic
leukemia/lymphoma in children".)

A hemoglobin level should be obtained annually from 1 to 13 years of age

to screen for anemia [1]. The anemia is usually due to iron deficiency
secondary to the restricted diet that many children with DS develop as a
result of delayed oral motor skills and dysphagia. However, anemia may
also be a sign of leukemia.

PERIODONTAL DISEASE

Periodontal disease is common in children and adults with DS and involves

inflammation, periods of acute infection, and pain [23]. The increased
frequency is thought to be due in part to alterations in mouth flora, with a
higher frequency of Actinobacillus actinomycetemcomitans compared with
controls [24]. Overlapping teeth, poor oral hygiene, and immunodeficiency
may also play a role [25]. (See "Gingivitis and periodontitis in children and
adolescents", section on 'Periodontitis' and "Periodontal disease in
children: Associated systemic conditions", section on 'Down syndrome'.)

Routine brushing should be encouraged. Dental visits are recommended

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

ATLANTOAXIAL INSTABILITY
The American Academy of Pediatrics Committee on Genetics and the
American Academy of Pediatrics (AAP) Committee on Sports Medicine and
Fitness recommend careful neurologic evaluation for signs and symptoms
consistent with spinal cord injury (eg, loss of motor skills, loss of bowel or
bladder control, neck pain, neck stiffness) as the most important clinical
predictor of symptomatic atlantoaxial instability (AAI) and dislocation [1,26].
The evaluating clinician should take a careful history and perform a
thorough physical examination, looking for evidence of neurologic
involvement. This clinical screening process should be done at least
annually. Caution regarding contact sports and trampoline use should be
discussed with families.

The AAP Committee on Genetics recommends obtaining lateral plain

cervical spine radiographs in the neutral position with odontoid and
anterior-posterior (A-P) views to examine for evidence of AAI or subluxation
in patients with myelopathic signs or symptoms [1]. Radiologic screening is
also suggested in children with DS prior to procedures that require
extremes of head position during induction of anesthesia or surgery [27]. Of
note, children do not have adequate vertebral mineralization and
epiphyseal development for accurate radiographic evaluation of the cervical
spine until at least three years of age.

The patient should be placed in a collar and referred immediately to a

pediatric neurosurgeon or pediatric orthopedic surgeon if significant
radiographic abnormalities are noted. Flexion and extension radiographs
may be performed prior to referral if no significant radiographic
abnormalities are present. The AAP Committee on Sports Medicine and
Fitness recommends that symptomatic children have magnetic resonance
imaging (MRI) to clarify the extent of spinal cord compression and that
appropriate surgical consultation be obtained to evaluate the need for
definitive treatment [26].
Nearly all people with AAI who have suffered a catastrophic injury to the
spinal cord have had preceding neurologic symptoms [26]. Asymptomatic
AAI is more common than symptomatic AAI in patients with DS, occurring
in 14 versus 3 percent, respectively, in one study [28]. Despite this, the
Special Olympics requires screening neck radiographs in children with DS
before participation. Children who are found to have AAI on these
radiographs but who lack neurologic symptoms should be followed closely
with repeat neurologic examinations (at least annually) [26].

BEHAVIOR AND PSYCHIATRIC PROBLEMS

Assessment and treatment of behavior and psychiatric problems should be

expeditious and should include evaluation of the problem at school and at
home, behavior management techniques, and medication as needed. (See
"Attention deficit hyperactivity disorder in children and adolescents: Clinical
features and diagnosis", section on 'Evaluation' and "Developmental-
behavioral surveillance and screening in primary care", section on 'Children
≥4 years'.)

SLEEP APNEA

Children with DS have an increased risk of obstructive sleep apnea (OSA)

because of soft tissue and skeletal alterations that lead to upper-airway
obstruction. Symptoms related to sleep apnea (snoring, restless sleep, and
sleep position) should be discussed at health supervision visits beginning
at age one year and continuing throughout childhood [29].
Polysomnography or pulse oximetry monitoring during sleep is
recommended in all children with DS by four years of age [1]. A predictive
model using questions from a validated sleep questionnaire, medication
history, patient age, anthropometric measurements, vital signs, and
physical exam findings had a negative predictive value of 73 percent for
mild OSA and 90 percent for moderate to severe OSA [30]. If confirmed in
validation studies, this tool could be used to determine which patients may
not need a diagnostic sleep study. (See "Mechanisms and predisposing
factors for sleep-related breathing disorders in children" and "Evaluation of
suspected obstructive sleep apnea in children" and "Management of
obstructive sleep apnea in children".)

FERTILITY AND REPRODUCTION

Ages for the onset and completion of puberty are typical for individuals with
DS. However, the mean stretched penile length and the mean testicular
volumes are significantly below average among adult men with DS
compared with unaffected men. Fertility is impaired in individuals with DS,
most likely secondary to primary gonadal deficiency [31]. Most published
data, however, suggest that 15 to 30 percent of women with DS are
capable of becoming pregnant, and their risk of having a child with DS is
approximately 50 percent [32]. Offspring without trisomy 21 seem to have
an increased risk for other congenital and developmental abnormalities.
Limited research also suggests that women with DS may have an
increased risk for miscarriages, premature births, and difficult labor [33].
Men with DS are generally thought to be infertile. However, there have
been various published case reports of men with DS fathering children [34-
36].

Individuals with various disabilities are at an increased risk for sexual

abuse. It is important for parents to discuss matters of sexuality, social skills
training, and measures to prevent pregnancy routinely with older children
and adults with DS.
ALZHEIMER DISEASE

Dementia that resembles Alzheimer disease is more common and occurs

at an earlier age in patients with DS. A medical evaluation should be
performed, including testing for thyroid disease, when the diagnosis of
Alzheimer disease is considered. Possible depression should also be
excluded. The diagnosis and treatment of dementia, including in patients
with DS, is discussed in detail separately. (See "Down syndrome: Clinical
features and diagnosis", section on 'Dementia/Alzheimer disease' and
"Evaluation of cognitive impairment and dementia" and "Treatment of
dementia".)

LIFE EXPECTANCY

Life expectancy in DS is shorter than that in the general population or in

individuals with other causes of intellectual disability. However, survival has
improved substantially [37-40]. In a Swedish study using national birth and
death registries, the median age at death increased from 3.6 years from
1969 to 1973 to 56.8 years from 1999 to 2003 [40]. The most common
main or contributing cause of death was pneumonia and other infections,
followed by congenital malformations, circulatory disease, and dementia. In
a similar study using United States death certificates from 1983 to 1997,
the improvement in survival was thought to be due to increased placement
of infants in homes rather than institutions, and to changes in treatment for
common causes of death, especially congenital heart disease [37].

In a retrospective cohort study conducted on 16,506 infants with DS born in

the United States between 1983 and 2003, the overall one-month and 1-,
5-, and 20-year survival probabilities were 98, 93, 91, and 88 percent,
respectively [41]. Survival improved modestly over the course of the study
in all but the neonatal period.

In the study using death certificate data, malignancies other than leukemia
were much less frequent in those with than without DS (standardized
mortality odds ratio 0.07) [37]. Possible mechanisms suggested for the low
rate of cancer include tumor suppressor genes on chromosome 21, a
slower rate of replication or higher rate of apoptosis in DS cells, or less
exposure to environmental risks.

Predictors of survival in DS may include race, gender, birth weight,

gestational age at birth, and presence of heart defects and other structural
anomalies [37,41-43]. In the death certificate study noted above, the
median age at death was higher among whites than other races [37]. In
contrast to the greater longevity of females in most populations, males with
DS appear to have a survival advantage [44,45]. In a series from Western
Australia, life expectancy was 58.6 years for the population and 3.3 years
longer for males than females [44].

BASIC SCIENCE RESEARCH AND FUTURE TREATMENT

OPTIONS

The development of DS mouse models has provided an opportunity to

study emerging pharmacotherapies that target intellectual disabilities
common in DS [46-48]. The overexpression of many genes found on
chromosome 21 contributes to learning deficits. Research has focused on
hippocampus function related to memory and learning. Areas of interest
include specific gamma-aminobutyric acid (GABA) receptor inhibitors, N-
methyl-D-aspartic (NMDA) receptor antagonists, and hippocampal dentate
gyrus neurogenesis. Preliminary basic science research shows
medications such as pentylenetetrazole (PTZ), memantine, and fluoxetine
may enhance learning in the DS mouse model. Further studies and clinical
trials are needed to show efficacy and safety of these medications in
children with DS.

ALTERNATIVE TREATMENTS

Oxidative stress, the imbalance between production and removal of

oxygen-derived free radicals, may contribute to some features of DS, such
as decreased immune function, premature aging, impaired mental function,
and malignancy [49]. In particular, the activity of superoxide dismutase (the
gene for which is located on chromosome 21) is increased [50]. Superoxide
dismutase is usually regarded as a protective enzyme since it scavenges
free superoxide molecules. However, in DS, the hydrogen peroxide
generated by superoxide dismutase-1 may become toxic in the presence of
ferrous iron (Fe2+). It forms the highly toxic hydroxyl radical (OH), which
can result in profound cellular damage [51].

Supplementation with antioxidant nutrients has been proposed as potential

therapy for DS. Treatments studied include supplementation with zinc,
selenium, megavitamins and minerals, vitamin A, vitamin B6, 5-
hydroxytryptamine, coenzyme Q10, and targeted nutritional intervention
[49,52,53]. These studies have methodologic flaws and provide no
convincing evidence that nutritional supplementation improves outcomes in
DS [54]. One randomized, controlled trial evaluated psychomotor and
language development in 156 infants treated for 18 months with daily oral
supplementation with one of four programs: antioxidants (selenium, zinc,
vitamin A, vitamin E, vitamin C), leucovorin (folinic acid), antioxidants and
leucovorin combined, or placebo. This trial found no significant differences
between the groups [53].
COUNSELING AND RESOURCES

Counseling may begin when a prenatal diagnosis of DS is made or

suspected [1]. The discussion should include the wide range of variability in
manifestations and prognosis. Medical and educational treatments and
interventions should be discussed. Initial referrals should be made to early
intervention, informative publications [55], parent groups, and advocacy
groups. In the early teen years, discussion and plans for transition to
adulthood should include employment/volunteer work [56], place of
residence, driving, and leisure activities.

Internet resources for parents and patients include the following:

● The Association for Children with Down Syndrome

● National Down Syndrome Society

A brochure entitled, "A promising future together: A guide for new and
expectant parents," available in English and Spanish, can be downloaded
from the National Down Syndrome Society website.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected

countries and regions around the world are provided separately. (See
"Society guideline links: Down syndrome".)

INFORMATION FOR PATIENTS

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

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

● Basics topic (see "Patient education: Down syndrome (The Basics)")

● Beyond the Basics topic (see "Patient education: Down syndrome

(Beyond the Basics)")

SUMMARY

● Management of Down syndrome (DS) requires an organized approach

to ongoing evaluation and monitoring for associated abnormalities and
prevention of common disorders. The Committee on Genetics of the
American Academy of Pediatrics (AAP) has provided
recommendations to assist clinicians in the care of children with DS
(table 1).

● The following evaluations are recommended:

• Plot growth on standard National Center for Health Statistics or

World Health Organization (WHO) growth charts; monitor for
 disturbances of growth associated with other disorders, such as
hypothyroidism or celiac disease, and for excessive weight gain.

• Pediatric cardiology evaluation, including an echocardiogram, in

the newborn period for congenital heart disease and continued
clinical cardiac monitoring in adolescence and adulthood for mitral
valve prolapse and aortic regurgitation.

• Newborn hearing screen and ongoing hearing screening

throughout childhood, plus monitoring for otitis media, which is a
common cause of hearing loss in children with DS.

• An ophthalmologic assessment before six months of age and then

approximately annually to screen for ophthalmologic disorders.

• Thyroid function testing in the newborn period with newborn state

screens and repeated at 6 months of age, 12 months of age, and
then yearly thereafter.

• Monitor for symptoms of celiac disease beginning at one year of

age. Screening is recommended if signs or symptoms develop.

• A complete blood count and differential at birth to evaluate for

myeloproliferative disorders and polycythemia; ongoing monitoring
for signs of leukemia.

• Check hemoglobin level annually starting at one year of age to

screen for iron deficiency anemia.

• Neurologic evaluation for signs and symptoms consistent with

spinal cord injury at each health supervision visit; symptomatic
children should have magnetic resonance imaging (MRI) to clarify
the extent of spinal cord compression.
 • Monitoring for symptoms related to sleep apnea at health
supervision visits beginning at age one year; polysomnography or
pulse oximetry during sleep is recommended in all children with
DS by four years of age.

● Life expectancy in DS is shorter than that in the general population or

in individuals with other causes of intellectual disability. However,
survival has improved substantially in the past two to three decades.

● Internet resources for parents and patients include the following:

• The Association for Children with Down Syndrome

• National Down Syndrome Society

Use of UpToDate is subject to the Subscription and License Agreement.

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Topic 2938 Version 38.0

GRAPHICS

Health supervision for children with Down syndrome

1
Birth
month 1 to 5 5 to 13 13 to 21
Prenatal to 1
to 1 years years years
month
year

Counseling
regarding
prenatal
screening test
and imaging
results

Plan for delivery

Referral to
geneticist

Parent-to-parent
contact, support
groups, current
books and
pamphlets

Physical exam for

evidence of
trisomy 21

Chromosomal
analysis to
confirm diagnosis

Discuss risk of
recurrence of
Down syndrome

Echocardiogram

Radiographic
swallowing
assessment if
marked
hypotonia, slow
feeding, choking
with feeds,
recurrent or
persistent
respiratory
symptoms, FTT
Eye exam for
cataracts

Newborn hearing
screen and
follow-up

History and
physician
examination
assessment for
duodenal or
anorectal atresia

Reassure
parents delayed
and irregular
dental eruption,
hypodontia are
common

If constipation, Any visit

evaluate for
limited diet or
fluids, hypotonia,
hypothyroidism,
GI malformation,
Hirschsprung

CBC to rule out

transient
myeloproliferative
disorder,
polycythemia

Hb annually; Annually
CRP and ferritin
or CHr if possible
risk iron
deficiency or Hb
<11 g

Hemoglobin Annually

TSH (may be part 6 and Annually

of newborn 12
screening) months

Discuss risk of
respiratory
infection

If cardiac surgery
or hypotonic:
evaluate apnea,
bradycardia, or
oxygen
desaturation in
car seat before
discharge

Discuss All health maintenance visits

complementary
and alternative
therapies

Discuss cervical All health maintenance visits

spine positioning,
especially for
anesthesia or
surgical or
radiologic
procedures

Review signs and All health maintenance visits

symptoms of
myopathy

If myopathic Any visit

signs or
symptoms: obtain
neutral position
spine films and, if
normal, obtain
flexion and
extension films
and refer to
pediatric
neurosurgeon or
orthopedic
surgeon with
expertise in
evaluating and
treating atlanto-
axial instability

Instruct to contact Biennially

physician for
change in gait,
change in use of
arms or hands,
change in bowel
or bladder
function, neck
pain, head tilt,
torticollis, or new-
onset weakness

Advise risk of All health maintenance visits

some contact
sports,
trampolines

Audiology
evaluation at six
months

If normal hearing Every 6

established, months
behavioral
audiogram and
tympanometry
until bilateral ear-
specific testing
possible. Refer
child with
abnormal hearing
to occupational
therapy.

If normal ear- Annually

specific hearing
established,
behavioral
audiogram

Assess for All health maintenance visits

obstructive sleep
apnea symptoms

Sleep study by
age four years

Ophthalmology
referral to assess
for strabismus,
cataracts, and
nystagmus

Refer to pediatric Annually Every 2 Every 3

ophthalmologist years years
or
ophthalmologist
with experience
with Down
syndrome

If congenital All visits

heart disease,
monitor for signs
and symptoms of
congestive heart
failure
Assess the All health maintenance visists
emotional status
of parents and
intrafamilial
relationships

Check for All health maintenance visits

symptoms of
celiac disease; if
symptoms
present, obtain
tissue
transglutaminase
IgA and
quantitative IgA

Early Health maintenance visits

intervention:
physical,
occupational, and
speech therapy

At 30 months,
discuss transition
to preschool and
development of
IEP

Discuss Health maintenance visits

behavioral and
social progress

Discuss self-help Health

skills, ADHD, maintenance
OCD, wandering visits
off, transition to
middle school

If chronic cardiac
or pulmonary
disease, 23-
valent
pneumococcal
vaccine at age >2
years

Reassure
regarding
delayed and
irregular dental
eruption

Establish optimal Health

dietary and maintenance
 physical exercise visits
patterns

Discuss
dermatologic
issues with
parents

Discuss physical
and psychosocial
changes though
puberty, need for
gynecologic care
in the pubescent
female

Facilitate Health
transition: maintenance
guardianship, visits
financial
planning,
behavioral
problems, school
placement,
vocational
training,
independence
with hygiene and
self-care, group
homes, work
settings

Discuss sexual Health

development and maintenance
behaviors, visits
contraception,
sexually
transmitted
diseases,
recurrence risk
for offspring

Do once at this age

Do if not done previously

Repeat at indicated intervals

FTT: failure to thrive; GI: gastrointestinal; CBC: complete blood count; Hb: hemoglobin; CRP: C-reactive
protein; CHr: reticulocyte hemoglobin; TSH: thyroid-stimulating hormone; IgA: immunoglobulin A; IEP:
Individualized Education Plan; ADHD: attention deficit hyperactivity disorder; OCD: obsessive-compulsive
disorder.

Reproduced with permission from Pediatrics, Vol. 128, Pages 393-406, Copyright © 2011 by the AAP.
Graphic 118957 Version 2.0
Contributor Disclosures
Kathryn K Ostermaier, MD, FAAP Nothing to disclose Helen V Firth, DM, FRCP,
DCH Nothing to disclose Jan E Drutz, MD Nothing to disclose Elizabeth TePas,
MD, MS Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group.
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