Brief
in
Trisomies
Paul A. Levy, MD,* Robert Marion, MD*
*Children’s Hospital at Montefiore, Bronx, NY
AUTHOR DISCLOSURE Drs Levy and Marion
have disclosed no financial relationships
relevant to this article. This commentary does
not contain a discussion of an unapproved/
investigative use of a commercial product/
device.
Health Supervision for Children with Down
Syndrome. Bull MJ; Committee on Genetics.
Pediatrics. 2011;128(2). Available at: http://
www.pediatrics.org/cgi/doi/10.1542/
peds.2011-1605. doi:10.1542/peds.2011-1605
Care of the Infant and Child with Trisomy 18
or Trisomy 13: A Care Book for Families. 3rd
ed. Barnes AM, Carey JC. Available at: http://
trisomy.org/wp-content/uploads/2014/08/
Carebook-updated-8-15-14.pdf
Chromosomal Disorders. Levy P, Marion RW.
In: Marcdante KJ, Kliegman RM, Jenson HB,
Behrman RE, eds. Nelson’s Essentials of
Pediatrics. 6th ed. Philadelphia, PA: Elsevier
Saunders; 2010:167–186
The Trisomy 18 Syndrome. Cereda A, Carey
JC. Orphanet J Rare Dis. 2012;7:81
Perspectives on the Care and Management
of Infants with Trisomy 18 and Trisomy 13:
Striving for Balance. Carey JC. Curr Opin
Pediatr. 2012;24(6):672–678. doi: 10.1097/
MOP.0b013e3283595031
104 Pediatrics in Review
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Errors in meiosis during the production of gametes lead to abnormalities of
chromosome structure or number. Chromosomal abnormalities occur in 0.5% to
1.0% of live births and cause trisomy syndromes such as 21, 13, and 18.
TRISOMY 21 (ALSO KNOWN AS DOWN SYNDROME)
Occurring in approximately 1 in 700 live births, trisomy 21 is by far the most
common trisomy. In 94% of patients, it is caused by nondisjunction, with
3 copies of chromosome 21 present in all cells. In 4.5% of patients, the extra
chromosome 21 is part of a translocation, the most common of which involves
chromosomes 14 and 21.
Although most children with trisomy 21 have normal birthweight and birth
length, they have a characteristic facial appearance, which includes brachy-
cephaly, a flattened occiput, a depressed nasal bridge, upslanting palpebral
fissures, epicanthal folds, and a large protruding tongue. Other features include
short, broad hands, often with a transverse palmar crease, and a wide gap be-
tween the first and second toes. Hypotonia may be severe enough to cause
significant feeding problems, with some infants requiring nasogastric feeding.
Individuals with trisomy 21 have many health issues. In the newborn period,
concerns include the following:
1) Congenital heart disease: Approximately 40% are born with a cardiac anomaly,
most of which involve abnormalities of the embryonic endocardial cushion.
Atrioventricular canal, ventriculoseptal, and atrioseptal defects are the most
common anomalies. All infants diagnosed as having trisomy 21 should have an
echocardiogram before hospital discharge.
2) Congenital gastrointestinal defect: Five percent to 10% have an obstructive lesion
of the small intestine. Duodenal atresia is most common, but annular pancreas
is also seen. In addition, 2% to 5% have obstruction from Hirschsprung
disease. Anal atresia can also occur. Surgery is usually necessary to repair these
obstructions.
3) Hematologic abnormalities: More than 50% exhibit polycythemia (hematocrit
level ‡65%). A smaller percentage has a markedly elevated white blood cell
count, suggestive of congenital leukemia. Known as a leukemoid reaction or
transient myeloproliferative disorder, it is benign, resolving on its own.
Treatment for the polycythemia is necessary for symptoms of hyperviscosity.
Trisomy 21 confers an increased risk (10- to 18-fold) of leukemia. Children
younger than 1 year develop acute nonlymphoblastic forms of leukemia;
older children, similar to the general population, predominantly contract
acute lymphoblastic leukemia.
4)Hypothyroidism and other endocrine abnormalities: Approximately 1% have
congenital hypothyroidism. The prevalence of hypothyroidism rises dramati-
cally with age, reaching approximately 20% by 21 years old. In most patients,
 autoimmune thyroiditis is the cause. Hyperthyroidism
is also more common, occurring in approximately 3%.
Monitoring of thyroid function is essential in the man-
agement of children with trisomy 21. Diabetes mellitus
and obesity also become more prevalent as affected chil-
dren age.
Medical issues in older individuals with trisomy 21
include the following:
1) Intellectual and developmental disabilities: As in the
general population, the spectrum of intellectual devel-
opment adheres to a bell-shaped curve; however, with
trisomy 21, the median IQ is approximately 60, rather
than 100. It is essential that all children with trisomy 21
receive early intervention services, including physical,
occupational, and speech therapy, as well as special
instruction, and other educational services, from as early
in life as is possible.
2) Other neurologic issues: There is increased risk of
developing seizures early in life, especially infantile
spasms, which occur in 1% to 3%. Individuals with
trisomy 21 are 6 times more likely than the general
population to develop a dementia-like syndrome similar
to Alzheimer disease.
3) Immune function: There is greater susceptibility to
infections, especially early in life.
4) Ophthalmologic: Strabismus and the development of early
cataracts are more common than in the general population.
5) Otolaryngologic: Obstructive apnea, and both sensori-
neural and conductive hearing loss are also more common.
Individuals with trisomy 21 must be followed by a mul-
tidisciplinary team of health-care providers with expertise in
the care of these children. As a guide, the American Acad-
emy of Pediatrics has published “Health Supervision for
Children with Down Syndrome.”
TRISOMY 18
The second most common trisomy is trisomy 18, occurring
in 1 in 3,000 to 1 in 8,000 live births with a ratio of females
to males of 3:1. More than 95% of trisomy 18 conceptuses are
lost as spontaneous abortuses.
Only 25% to 40% of affected infants live beyond the first
month, and only 2% to 8% survive past their first year.
Among survivors, severe intellectual disability, coupled with
serious chronic medical problems, is the rule. The decision
to provide extraordinary care to infants with trisomy 18 must
be tailor-made for each child, with an ongoing dialogue
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between the primary care provider, the multidisciplinary
team, and the child’s family.
Virtually all cases of trisomy 18 result from an extra copy
of the chromosome; unlike trisomy 21, there are no cases
from unbalanced translocations. Most affected infants are
small for gestational age with a characteristic phenotype,
including dolichocephaly with a prominent occiput, micro-
gnathia with a receding jaw, short palpebral fissures, and
low-set malformed ears. Additional features include a short
sternum and anomalies of the feet, including prominent
talus rocker-bottom feet and talipes equinovarus (club-feet).
The hands are striking, with hypoplastic nails, fingers held
in a clenched posture, and the second and fifth digits over-
lapping the third and fourth digits.
TRISOMY 13
The third most common trisomy occurs in 1 in 12,000 live
births. Similar to trisomy 18, the condition is nearly always
fatal in the first year of life; less than 10% of infants with
trisomy 13 survive beyond their first birthday.
Generally, infants with this condition have intrauterine
growth restriction and microcephaly. Midline facial defects
such as cyclopia (single orbit) and cleft lip and palate are
common, as well as midline central nervous system anom-
alies, such as alobar holoprosencephaly. The forehead is
generally sloping, the ears are often small and malformed,
and severe anomalies of the eyes (anophthalmia or micro-
phthalmia) occur. Postaxial polydactyly is common, as are
clubfeet or rocker-bottom feet. Hypospadias and cryptor-
chidism are common in males, and females generally have
hypoplasia of the labia minora.
As in trisomy 18, anomalies of virtually every organ sys-
tem are seen in infants with trisomy 13. Most infants have
congenital heart disease. Abnormalities of the lungs, liver,
kidneys, and pancreas are often seen.
GENETIC COUNSELING
The common trisomies are most often diagnosed prena-
tally or at birth. Because advanced maternal age is a risk
for nondisjunction, prenatal testing is routinely offered to
pregnant women who will be 35 years or older at their child’s
birth. Amniocentesis remains the gold standard for identi-
fying fetal chromosome abnormalities, but pregnancies at
risk can now be identified by noninvasive prenatal screen-
ing, which identifies fetal DNA from maternal blood.
Vol. 39 No. 2 FEBRUARY 2018 105
 The recurrence risk for parents with a child with trisomy biochemical screening, ultrasonography, amniocentesis,
21 depends on the child’s cytogenetic findings. If nondis- and chorionic villous sampling are all available.
junction led to trisomy 21, the recurrence risk is 1% higher
than the mother’s age-specific risk for women younger than
COMMENT: With time, and experience, our view of chil-
35 years, and only the age-specific risk for women older than
dren with trisomies has changed, often in dramatic ways.
35 years. For the two-thirds of cases when an unbalanced
In the past, for example, children with Down syndrome
translocation occurs de novo, the recurrence risk is 1%. In
either were not considered for corrective cardiac surgery at
the remaining one-third of cases, where 1 of the parents has
all or their referral for surgery was commonly delayed to
a balanced translocation, if the mother is the carrier, the
the point that onset of shunt reversal with pulmonary
recurrence risk is 10% to 15%; if the father is the carrier, the
hypertension (Eisenmenger syndrome) made correction
risk is only 2% to 5%.
useless. Even more fundamentally, how many children
Genetic counseling for parents of children with trisomy
with Down syndrome were in effect stockpiled in institu-
18 is similar to that in trisomy 21. Prenatal testing, as
tions to “protect” their families from having to cope with so
described for trisomy 21, is available.
“hopeless” a child? And we don’t need long memories to
As in the other trisomies, most cases of trisomy 13 are
recall the days when resuscitative efforts were not even a
caused by nondisjunction, but the frequency of unbal-
consideration for any child with trisomy 13 or 18. Change
anced translocations (20%) is higher than in trisomy 21
can be for the better.
or trisomy 18. Recurrence risk, as with trisomy 21, in-
creases with advancing maternal age. For prenatal diag- – Henry M. Adam, MD
nosis, noninvasive prenatal screening, maternal serum Associate Editor, In Brief

ANSWER KEY FOR FEBRUARY 2018 PEDIATRICS IN REVIEW

Pediatric Solid Tumors of Infancy: An Overview: 1. E; 2. C; 3. A; 4. D; 5. A.
Recognizing and Referring Children with Posttraumatic Stress Disorder:
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Kawasaki Disease: 1. A; 2. C; 3. B; 4. A; 5. C.

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 Trisomies
Paul A. Levy and Robert Marion
Pediatrics in Review 2018;39;104
DOI: 10.1542/pir.2016-0198

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 Trisomies
Paul A. Levy and Robert Marion
Pediatrics in Review 2018;39;104
DOI: 10.1542/pir.2016-0198

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/content/39/2/104

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