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Background
Down syndrome is by far the most common and
best known chromosomal disorder in humans and
the most common cause of intellectual disability.[1,
2, 3, 4, 5]
It is characterized by mental retardation,
dysmorphic facial features, and other distinctive
phenotypic traits. Down syndrome is primarily
caused by trisomy of chromosome 21; this is the
most common trisomy among live births. The term
mongolism was once commonly used but is now
considered obsolete.[6, 7, 8]
Like most diseases associated with chromosomal
abnormalities, trisomy 21 gives rise to multiple
systemic complications as part of the clinical
syndrome. This chromosomal anomaly leads to
both structural and functional defects in patients
with Down syndrome. However, not all defects
occur in each patient; there is a wide range of
phenotypic variation.
Pathophysiology
The extra chromosome 21 affects almost every
organ system and results in a wide spectrum of
phenotypic consequences. These include lifethreatening complications, clinically significant
alteration of life course (eg, mental retardation),
and dysmorphic physical features. Down
syndrome decreases prenatal viability and
increases prenatal and postnatal morbidity.
Affected children have delays in physical growth,
maturation, bone development, and dental
eruption.
Two different hypotheses have been proposed to
explain the mechanism of gene action in Down
syndrome: developmental instability (ie, loss of
chromosomal balance) and the so-called genedosage effect.[9] According to the gene-dosage
effect hypothesis, the genes located on
chromosome 21 have been overexpressed in cells
and tissues of Down syndrome patients, and this
contributes to the phenotypic abnormalities.[10]
The extra copy of the proximal part of 21q22.3
appears to result in the typical physical phenotype,
which includes the following:
Mental retardation - Most patients with
Down syndrome have some degree of
cognitive impairment, ranging from mild
(intelligence quotient [IQ] 50-75) to
severe impairment (IQ 20-35); patients
show both motor and language delays
during childhood
Characteristic facial features
Hand anomalies
PRESENTATION
History
When recording the history from the parents of a
child with Down syndrome, the clinician should
include the following[14] :
Parental concern about hearing, vision,
developmental delay, respiratory
infections, and other problems
Feeding history to ensure adequate caloric
intake
Prenatal diagnosis of Down syndrome
Vomiting secondary to gastrointestinal
(GI) tract blockage by duodenal web or
atresia
Absence of stools secondary to
Hirschsprung disease
Delay in cognitive abilities, motor
development, language development
(specifically expressive skills), and social
competence
Arrhythmia, fainting episodes,
palpitations, or chest pain secondary to
heart lesion
Symptoms of sleep apnea, including
snoring, restlessness during sleep,
difficulty awaking, daytime somnolence,
behavioral changes, and school problems
Symptoms of atlantoaxial instability include the
following:
About 13-14% of patients have
radiographic evidence of atlantoaxial
instability but no symptoms.
Only 1-2% of patients have symptoms that
require treatment.
Symptoms include easy fatigability, neck
pain, limited neck mobility or head tilt,
torticollis, difficulty walking, change in
gait pattern, loss of motor skills,
incoordination, clumsiness, sensory
deficits, spasticity, hyperreflexia, clonus,
extensor-plantar reflex, loss of upper-body
strength, abnormal neurologic reflexes,
change in bowel and bladder function,
increased muscle tone in the legs, and
changes in sensation in the hands and feet.
These symptoms often remain relatively
stable for months or years.
In rare cases, the symptoms progress to
paraplegia, hemiplegia, quadriplegia, or
death.
Physical Examination
Patients with trisomy 21 have characteristic
craniofacial findings, such as an anteriorly and
Characteristic
flat facies with hypertelorism, depressed nasal
bridge, and protrusion of tongue, as well as single
palmar simian crease in 2-year-old girl with Down
syndrome. Image courtesy of L. Dourmishev, MD,
PhD, DSc.
Mouth and teeth
Characteristic features include a (relatively) small
mouth with a tendency for tongue protrusion, a
fissured and furrowed tongue, mouth breathing
with drooling, a chapped lower lip, angular
cheilitis, partial anodontia (50%), tooth agenesis,
malformed teeth, delayed tooth eruption,
microdontia (35-50%) in both the primary and
secondary dentition (see the image below),
hypoplastic and hypocalcified teeth, malocclusion,
taurodontism (0.54-5.6%), and increased
periodontal destruction. Cleft lip or palate may
occur but is rare.
Small auricle
and anomalies of folds in patient with Down
syndrome. Image courtesy of L. Dourmishev, MD,
PhD, DSc.
Neck
The neck is typically broad and short, with excess
skin on the back. Atlantoaxial instability (14%)
can result from laxity of transverse ligaments that
ordinarily hold the odontoid process close to the
anterior arch of the atlas. Laxity can cause
backward displacement of the odontoid process,
leading to spinal cord compression in about 2% of
children with Down syndrome.
Chest and abdomen
The internipple distance is decreased. The
abdomen is frequently protuberant. Diastasis recti
and umbilical hernia (see the image below) may
occur.
Patient with
Down syndrome with protuberant abdomen and
umbilical hernia. Image courtesy of L.
Dourmishev, MD, PhD, DSc.
Skin
Xerosis, localized hyperkeratotic lesions, elastosis
serpiginosa, alopecia areata (< 10%), vitiligo,
folliculitis, abscess formation, and recurrent skin
infections are observed.[22, 23] Distal axial triradius
in the palms, transverse palmar creases, a single
G-banded
karyotype showing trisomy 21 (47,XY,+21).
G-banded
karyotype showing trisomy 21 of isochromosome
arm 21q type [46,XY,i(21)(q10)].
Interphase fluorescence in situ hybridization
Fluorescence in situ hybridization (FISH) may be
used for rapid diagnosis. It can be successful in
both prenatal diagnosis and diagnosis in the
neonatal period.
Occult mosaicism for trisomy 21 may partially
explain the previously described association
between family history of Down syndrome and
risk of Alzheimer disease. Screening for
mosaicism with FISH is indicated in selected
patients with mild developmental delay and those
with early-onset Alzheimer disease.[44]
Evaluation of the proportion of cells with trisomy
21 in mosaic trisomy 21 includes the following[45] :
Lymphocyte preparations
Buccal mucosa cellular preparations
FISH
Scoring frequency of trisomic cells
Measurement of immunoglobulin G
Measurement of immunoglobulin (Ig) G levels
focuses on identifying deficiencies of subclasses 2
and 4. Decreased levels of IgG subclass 4 is
significantly correlated with bacterial infections.
These deficits in cellular immunity have also been
documented in individuals with gingivitis and
periodontal disease.
Radiography and Ultrasonography
MEDICATION
Medication Summary
Drug therapy is not currently a component of the
standard of care for Down syndrome. Medications
are indicated only for symptomatic treatment of
pain. Obviously, prolonged use of analgesics
without diagnostic evaluation and an
understanding of the underlying cause should not
be encouraged. No particular analgesic is superior.
Diuretics and digoxin should be used to manage
congestive heart failure secondary to congenital
heart defect.
Analgesics, Other
Class Summary
Pain control is essential to quality patient care. It
ensures patient comfort and promotes pulmonary
toilet, and analgesics have sedating properties that
are beneficial for patients who have sustained
trauma or injuries.
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Acetaminophen and codeine (Tylenol #3,
Capital and Codeine)
Codeine is a centrally acting analgesic;
acetaminophen is a peripherally acting analgesic.
The combination is indicated for treatment of mild
to moderately severe pain. Tablets contain
acetaminophen 300 mg and codeine phosphate 30
mg; elixir contains acetaminophen 120 mg and
codeine 12 mg per 5 mL.
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Morphine sulfate (Duramorph, Astramorph,
MS Contin, Oramorph SR)
Morphine is a narcotic drug that interferes with
opioid receptors; it mainly acts on the central
nervous system (CNS) and the gastrointestinal
(GI) tract.
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Ibuprofen (Motrin, Advil, Caldolor)
Ibuprofen is a member of the propionic acid group
of nonsteroidal anti-inflammatory drugs
(NSAIDs). It has anti-inflammatory, analgesic, and
antipyretic activity. Its mode of action is not clear
but might be related to prostaglandin synthetase
inhibition.
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Naproxen (Aleve, Anaprox, Naprosyn,
Naprelan)
Naproxen is an NSAID of the arylacetic acid
group. It inhibits prostaglandin synthesis.
Antidysrhythmics, Ia
Class Summary
Antidysrhythmics may improve morbidity in
patients with congestive heart failure secondary to
congenital heart defect.
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Digoxin (Lanoxin)
Digoxin is a cardiac glycoside with direct
inotropic effects in addition to indirect effects on
the cardiovascular system. It acts directly on
cardiac muscle, increasing myocardial systolic
contractions. Indirect actions result in increased
carotid sinus nerve activity and enhanced
sympathetic withdrawal for any given increase in
mean arterial pressure.
Diuretics, Other
Class Summary
Diuretics should be used to manage congestive
heart failure secondary to congenital heart defects.
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Furosemide (Lasix)
Furosemide increases excretion of water by
interfering with the chloride-binding cotransport