SYNDROMES ASSOCIATED WITH CONOTRUNCAL DEFECTS
|
Conotruncal anomalies are
malformations of the great vessels, arising from the embryological structures
of the conus and truncus, and account for about 30% of congenital heart defects
(CHD).
·
Associated
extracardiac anomalies, typically affecting the neck and head, result in apparently
different clinical syndromes:
o
DiGeorge
(DGS),
o
Shprintzen,
o
Velo-cardio-facial
syndrome (VCFS)
o
Conotruncal
anomaly face syndromes.
·
A
microdeletion of 22q11.2 has been shown to be associated with these anomalies
in greater than 80% of cases (1,2).
·
The
syndromes have been grouped together under the acronym 'CATCH-22' (3).
o
Cardiac defects,
o
Abnormal facies,
o
Thymus aplasia or hypoplasia,
o
Cleft palate,
o
Hypocalcemia,
o
22
denoting the deletion on chromosome 22.
o
Mental
retardation, immunologic deficiency, hypocalcemia and other mild to severe
disease are associated with CATCH-22.
o
Recently
it was suggested to abandon the acronym CATCH-22 and instead to use mainly
deletion 22q11.2 (4).
|
|
Frequency of |
|
1. Isolated (non familial). |
20-30% |
|
2. Syndromes associated with thymic and facial anomalies:
|
|
22q11.2 DELETION AND CHD |
·
The prevalence
of del.22q11.2 in the general population is high (1:4000 live births) (5).
·
The
prevalence in pediatric cardiology series depends on the specific subgroups
examined.
o
Marino
et al. (6) found that 88 of 931 (9.4%) infants and children with
CHD examined for this purpose had a microdeletion. One case only had an
isolated cardiac defect; the remaining 87 demonstrated features of
DiGeorge/VCFS, such as facial anomalies, immune defects, palatal anomalies,
neonatal hypocalcemia and mental retardation. Prenatal ultrasound has obvious
limitations for most of these features, but our study has indicated that an
absent or hypoplastic thymus may be a useful additional marker for the
deletion.
·
In
utero, the fetal
thymus is well developed and is easily visualized with high resolution
ultrasound (7). It is best
visualized in the 'three-vessel' view, a plane commonly used in assessment of
fetal conotruncal and aortic arch lesions (8). As absence and hypoplasia of the
thymus is associated with CATCH-22, it is possible that visualization of the
thymus on ultrasound can be used as a marker in the detection of del.22q11.2.
o
There
is a sensitivity of 90% in prediction of the 22q11.2 deletion when the fetal
thymus is hypoplastic or absent, in association with a cardiac anomaly.
o
The
thymus may be used as a sonographic marker to identify a group with CHD in whom
targeted examination of del.22q11.2 is indicated (9).
·
The
prevalence of 22q11.2 in a recent study was:
o
6.7% in all cardiac anomalies with
normal karyotype,
o
13.1%
in the subgroup with conotruncal anomalies.
·
The
deletion is frequently found in:
o
interrupted
aortic arch, particularly type B (45%),
o
absent
pulmonary valve syndrome (50%) ) Johnson et al. (10), Iserin et al
(11) and Boudjemline et al (12) that absent pulmonary valve
syndrome comprises over 40% of cases associated with 22q11.2 deletion).
o
truncus
arteriosus communis (30%),
o
pulmonary
atresia with VSD (21%)
o
tetralogy
of Fallot (14%) (11,13).
o
occasionally
present in double outlet right ventricle (13) and transposition of the great
arteries (14) and can be an incidental finding in non-conotruncal anomalies
such as hypoplastic left heart syndrome (15), isomerism (16) or others.
|
|
Chaoui (17) (prenatal) n = 76 (%) |
Boudjemline (12) prenatal) n = 261 (%) |
Iserin (11) (neonatal) n = 104 (%) |
Goldmuntz (13) (pediatric) n = 251 (%) |
|
Interruption of the aortic arch |
66.7 |
45.4 |
89 |
50 |
|
Truncus arteriosus |
33.3 |
31.0 |
41 |
34.5 |
|
Absent pulmonary valve syndrome |
50.0 |
37.5 |
40 |
|
|
Tetralogy of Fallot |
9.0 |
14.0 |
26 |
15.9 |
|
Pulmonary atresia with VSD |
0 |
21.5 |
46 |
|
|
Double outlet right ventricle |
0 |
Not assessed |
Not assessed |
5 |
|
Transposition of the great
arteries |
0 |
Not assessed |
Not assessed |
0 |
|
Complex malpositions |
0 |
0 |
Not assessed |
Not assessed |
|
VSD with conal septum
malalignment |
Not assessed |
Not assessed |
67 |
33.3 |
REFERENCES |