Congenital malformations - Edocr

Chapter 13
Cleft Lip and Palate
BRAD ANGLE
INTRODUCTION
Orofacial clefts (cleft lip [CL], cleft palate [CP])
are among the most common of all major birth
defects. CL may occur either in association with
CP or in the absence of CP, and is generally referred
to as “cleft lip with or without cleft palate”
(CL/P). CL/P is etiologically and genetically distinct
from CP, which typically occurs without associated
CL. CL/P and CP may occur as isolated
congenital anomalies (nonsyndromic orofacial
clefts) or as components of genetic disorders or
syndromes.
EPIDEMIOLOGY/ETIOLOGY
The overall incidence of CL with or without cleft
palate is approximately 1/1000, ranging from
1/500 to 1/2500 in different populations, varying
with geographic location, ethnic group, and
socioeconomic conditions. 1 CL may be unilateral
(80%) or bilateral (20%) and when unilateral,
it is more common on the left side (70%).
Approximately 85% of cases of bilateral CL and
70% of unilateral CL are associated with CP. The
incidence of isolated CP is approximately 1 in
2500 2 and Robin sequence occurs in approximately
1 in 14,000 live births. 3
Both genetic and environmental factors are
thought to play important roles in the causation
of orofacial clefts (multifactorial inheritance). It
is likely that there are multiple genes that may
play a role in cleft malformations. In addition to
single gene disorders that cause syndromic
forms of orofacial clefts, it has been estimated
that at least six genes, and possibly many more,
could be involved in the development of nonsyndromic
orofacial clefts. 4,5 It has been suggested
that causation does not involve “major
genes” but rather the combination of many genes,
each conferring only a small risk, in conjunction
with a significant environmental component. 6
Results of a number of studies suggest that involvement
of the pathways of folate metabolism
may play a role in the etiology of orofacial clefts. 5
Some studies have suggested that women with a
specific mutation (C677T) in the methylenetetrahydrofolate
reductase (MTHFR) gene have an
increased risk of having an offspring with an
orofacial cleft. 7,8
Many epidemiological studies have demonstrated
a relation between specific environmental
factors and teratogens and the development
of orofacial clefts. Environmental factors such as
cigarette smoking appear to play a role in the
occurrence of these malformations. 5 Alcohol use
in pregnancy increases the risk of CL/P but not
CP only. 9 The anticonvulsants phenytoin and
valproic acid are associated with an increased
risk for a variety of congenital anomalies including
orofacial clefts. 10 It is unclear whether CP
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