Congenital malformations - Edocr

CHAPTER 13 CLEFT LIP AND PALATE 95
These disorders involve abnormalities of the
hair, teeth, and skin. Some ectodermal dysplasias
also are associated with congenital limb
anomalies involving absence of fingers or toes
(ectrodactyly/split hands and feet). Mutations
in the TP63 gene cause the ectrodactyly, ectodermal
dysplasia, and cleft lip/palate (EEC)
syndrome and Hay-Wells anklyoblepharonectodermal
dysplasia–clefting (AEC) syndrome.
CL with or without palate may occur in a variety
of chromosome abnormalities, particularly in
association with partial deletion of the short arm
of chromosome 4. Deletion 4p syndrome (4p- or
Wolf-Hirschhorn syndrome) is characterized by
ocular hypertelorism, broad or beaked nose, microcephaly,
low-set ears, and CL and/or CP.
While the vast majority of CL malformations
are lateral clefts, median or midline clefts (through
the center of the upper lip) are very rare and represent
approximately 0.5% of all CL defects. Median
CL may occur as an isolated anomaly or as
part of a number of malformation syndromes.
The most common disorders associated with a
median CL are holoprosencephaly, Trisomy 13,
and oral-facial-digital (OFD) syndrome.
Holoprosencephaly is a malformation in
which impaired cleavage of the embryonic forebrain
is the major feature. Typical craniofacial
features include hypertelorism, various degrees
of abnormal nasal development, and occasional
median CL. Infants with Trisomy 13 may have
holoprosencephaly and/or median CL.
Oral-Facial-Digital type 1 syndrome is an
X-linked dominant disorder affecting mainly
females, which is characterized by multiple
frenuli between the buccal mucous membrane
and alveolar ridge, median CL and/or CP, lobulated
or bifid tongue, and a variety of digital
anomalies including asymmetric digits, syndactyly,
and polydactyly.
As previously mentioned, a number of teratogens
may cause CL/P including alcohol,
phenytoin, and valproic acid. Each of these
teratogens is associated with characteristic
craniofacial features and a variety of congenital
anomalies most commonly including digital
TABLE 13-2 Genetic Disorders Associated
with Cleft Palate
22q11.2 deletion syndrome and other
chromosome abnormalities
Fetal alcohol syndrome
Hay-Wells ectodermal dysplasia
Kniest dysplasia
Oto-Palato-digital syndrome
Robin sequence
Spondyloepiphyseal dysplasia congenita
Stickler syndrome
Treacher Collins syndrome
Van der Woude syndrome
abnormalities, congenital heart defects, and genitourinary
anomalies.
Cleft Palate
Approximately 15–50% of infants with CP without
CL have additional congenital abnormalities and
there are a number of specific genetic disorders
in which CP is a frequent finding (Table 13-2).
One of the disorders most frequently associated
with CP is the 22q11.2 deletion syndrome.
This syndrome is caused by a submicroscopic
deletion of chromosome 22 detected by fluorescence
in situ hybridization (FISH). With an
incidence of 1/4000, 22q11.2 deletion syndrome
is the most common chromosome microdeletion
syndrome and one of the most common of
all recognized genetic disorders. The most frequently
observed features of this disorder include
congenital heart defects, particularly
conotruncal defects (tetralogy of Fallot, interrupted
aortic arch, ventricular septal defect),
palatal abnormalities (CP, abnormal velopharyngeal
musculature and function), hypocalcemia,
immune deficiency, and characteristic facial
features (Table 13-3).
The 22q11.2 deletion syndrome includes the
phenotypes previously described as DiGeorge
syndrome (heart defects, hypocalcemia, absent
or hypoplastic thymus) and velocardiofacial