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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 5, September/October 2016
AFRICA
289
patients with an indication for surgery who were operated on,
79% survived. On the other hand, for the patients having a
surgical indication but were not operated on, only 31% survived.
Discussion
CHD in DS is reported to be as high as 40 to 63% and is a major
cause of morbidity and early mortality in these patients.
4,6,8,13
It has been suggested that when characterising the profiles
and types of CHD in DS, the dominant lesions observed are
variable according to the different geographical areas around
the world.
7,8
Hence, for a given country, to know the profile and
characteristics of CHD in DS is of great importance, first to
improve survival by timely treatment of cardiac anomalies,
10
and
second to apply appropriate preventative measures.
In this study, we sought to determine the distribution of
CHD in DS in the Moroccan setting. As our institution is a
referral centre for approximately one-quarter of the population
of our country, the results observed in this study may reflect the
national trends of CHD in DS.
AVSD was the most common cardiac abnormality and VSD
the second most common abnormality. Together, AVSD and
VSD cases represented 50% of CHDs in our setting. ASD,
isolated PDA and tetralogy of Fallot were recorded at rates of
19.9, 16 and 5%, respectively.
DS is the most common autosomal abnormality. The
frequency is about one case in 600 live births.
1-3
This syndrome,
which is by far the most common and best known chromosomal
disorder in humans, is characterised by intellectual disability,
dysmorphic facial features and other distinctive phenotypic
traits.
1-4,6
DS is primarily caused by trisomy of chromosome 21, which
is the most common trisomy among live births. In 94% of
patients with DS, full trisomy 21 is the cause; mosaicism (2.4%)
and translocations (3.3%) account for the remaining cases.
14,15
Approximately 75% of the unbalanced translocations are
de
novo
, and approximately 25% result from familial translocation.
14
Two different hypotheses have been proposed to explain the
mechanism of gene action in DS: developmental instability (i.e.
loss of chromosomal balance) and the so-called gene-dosage
effect.
15
According to the gene-dosage effect hypothesis, the genes
located on chromosome 21 have been overexpressed in cells and
tissues of DS patients, and this contributes to the phenotypic
abnormalities.
16
There has been much interest in trying to identify the exact
location of CHD susceptibility genes. Although trisomy 21 is
a risk factor for CHD, it is not a sufficient requirement (about
40–60% of people with trisomy 21 do not have CHD).
Molecular mapping studies suggested the presence of
a ‘critical region’ that is responsible for the various CHD
phenotypes, and narrowed the region to D21S3 (defined by
VSDs) through to PFKL (defined by tetralogy of Fallot),
containing 39 human genes and 25 predicted genes. One of these
genes, DSCAM, is known to mediate cell–cell adhesion, thought
to be essential to the process of cellular adhesion and fusion of
endocardial cushions. It is speculated that the overexpression
of DSCAM can lead to a disturbance of normal epithelial–
mesenchymal transformation and/or mesenchyme cell migration
or proliferation, thus resulting in an increase in the adhesive
property of the cushion fibroblasts, leading to the various heart
defects.
17
As observed during this study, median age of the mothers at
delivery was 39 years (16–47). The occurrence of DS is strongly
dependent on maternal age, and advanced maternal age remains
the only well-documented risk factor for maternal meiotic
non-disjunction. With a maternal age of 45 years, the risk is one
in 30 to 50 live births.
18
However, understanding of the basic
mechanism behind the maternal age effect is lacking. Some
studies also suggest a role for consanguinity
19
(Fig. 1).
In our study, the most common lesion was AVSD (29%),
followed by VSD (21.5%) and ASD (19.9%). The most common
associations of CHD were AVSD
+
ASD (10%) and VSD
+
ASD
(7.8%) (Table 1).
In the international literature, the most common CHDs in DS
from reports from western European countries and the USA are
the following: endocardial cushion defect (43%), which results
in AVSD/AV canal defect; VSD (32%); secundum atrial septal
defect (10%); tetralogy of Fallot (6%); and isolated PDA (4%).
About 30% of patients have several cardiac defects.
3,4,6,13
However,
in Asia, isolated VSDs have been reported to be the most
common defect, observed in about 40% of patients,
20
whereas in
most reports from Latin America, the secundum type of ASD is
suggested to be the most common lesion.
8,11
This study on CHD in DS in the Moroccan setting exhibited
similar results to those of Western countries in terms of major
CHDs in DS, but the prevalence rates of ASVD and VSD were
lower. This has also been reported by others
1,7,8,20
and reinforces
the findings of a variation in profile and type of CHD in DS in
the different geographical areas around the world.
Since our study exhibited similar CHD dominant lesions in
DS to those of Morocco’s neighbouring European countries, it
suggests that, despite the level of development of the different
countries, a combination of factors and regional proximity
most likely plays a significant role in such similarities. However,
regional proximity alone cannot explain all the differences, as
studies in African countries that also have regional proximity
with Europe, such as Libya, have exhibited results that globally
encompassed the spectrum of CHD in DS seen in Europe but
with quite different rates in the different CHDs.
21
As illustrated
by the differences in reported rates of the different CHDs in
Table 2. Fate of patients with Down syndrome
and congenital heart disease
Patients with DS and CHD
Number of patients (%)
(
n
=
128)
• Dead
18 (14.1)
• Alive
72 (56.3)
• Lost to follow up
38 (29.7)
Patients with an indication for surgery
69/128 (54)
Patients operated on
42/69 (61)
• Dead
8/42 (19)
• Alive
33/42 (79)
• Lost to follow up
1/42 (2)
Patients not operated on
13/69 (19)
• Dead
9/13 (69)
• Alive
4/13 (31)
• Lost to follow up
14/69 (20)
Patients with no indication for surgery
59/128 (46)
• Dead
1/59 (2)
• Alive
35/59 (59)
• Lost to follow up
23/59 (39)