Congenital malformations - Edocr

CHAPTER 1 DYSMORPHOLOGY 5
Almost 15–30% of all pediatric hospitalizations
in the United States are related to birth defects,
and approximately $8 billion is spent annually
to provide medical and rehabilitative care for affected
children in the United States alone. 19
EMBRYOLOGY OF BIRTH
DEFECTS
Since all congenital anomalies are a result of
aberrant structural development before birth,
basic understanding of normal and abnormal
embryogenesis and fetal development is important
for clinicians providing care for these infants.
Prenatal development can be divided into
three time periods: the preembryonic period or
implantation stage, extending from the time of
fertilization to the end of the second week of gestation;
the embryonic stage, from the beginning
of the third week to the end of the eighth week;
and the fetal stage, from the ninth week until
birth (Fig. 1-1). 20 The preembryonic stage starts
with the fertilization and formation of the zygote
which transforms into a blastocyst by the end of
the first week. Characterized by the presence of
pluripotent cells and rapid cell proliferation, implantation
of the blastocyst is complete by the
end of the second week. The presence of these
pluripotent cells is also responsible for the “all
or none” effect of teratogens during this period.
An environmental insult during this period will
either kill the embryo or produce no harm if the
embryo survives.
The embryonic stage is the time of primary
tissue differentiation and formation of definitive
organs. During the third week of gestation, it starts
with the formation of primitive streak, notochord,
and three germ layers from which all embryonic
tissues and organs develop. During the following
Preorganogenesis
Fertilization to
Bilaminar disc
Formation
Embryonic Period
(weeks)
Lip
Heart
U.Limb
L.Limb
Palate
Central Nervous System
Ear
Fetal Period
(weeks)
1 2 3 4 5 6 7 8 9 10 11 12 20 38
Eyes
Teeth
External Genitalia
Death
Major Malformations
Functional Defects and Minor Malformations
Figure 1-1. Susceptibility to teratogenesis for different organ systems. Solid bar indicates highly
sensitive periods. (Reprinted with permission from Clayton-Smith J, Donnai D. Human Malformations.
In: Rimoin DL, Connor JM, Pyeritz RE, eds. Emery and Rimoin’s principles and practice of medical
genetics Vol I. 3rd ed. New York; Edinburgh: Churchill Livingstone; 1997:383–94.) 20