SYNDROMAL ASSOCIATIONS OF COMMON ORIGIN

OF THE CAROTID ARTERIES

Theadis R. Wells, HT(ASCP1, and Benjamin H. Landing, MD Departments of

Pathology and Laboratory Medicine, Childrens Hospital Los Angeles and University of
Southern California School of Medicine, Los Angeles, California

William R. Shankle, MD 0 Departments of Neurology and Psychobiology, University

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of California at Irvine, Irvine, California

The term “common origin of the carotid arteries” (COCA) has been proposed to replace the older
terms “or@in cf the left carotid arteryjiom the innominate stem’’ and “bicarotid trunk with anomalous
right or lefi subclavian artery.” These anatomic patterns are usually reported to occur in about 11 % of
whites and 20-25% of blacks and have been reported to have increased frequenv in patients with
esophageal atresia-tracheoesophageal fistula, DiGeorge anomaly, and anomalous origin of the left coro-
nary artery from the pulmonary artery. COCA is a significant, ij not invariant, feature of the great
arteries in the condition usually called in the more recent literature “anomalous origin of the innominate
artery,” the most frequent cause of symptomatic tracheal compression by anomalous systemic arteries.
For personal use only.

Analysis of associations of COCA with various other congenital cardiovascular lesions showed, in
addition, signifiCnt association with congenital polyvalvular disease, truncus arteriosus, aortico-
pulmonary window, trisomy 13, 18, and 21 syndromes, acrocephalosyndactyly (especially Apert syn-
drome), tetralogy of Fallot not associated with DiGeorge anomab, and clinical Noonan phenotype.
Pentalogy of Cantrell was associated with no increase in incidence of COCA.

KEY WORDS: carotid arteries.

INTRODUCTION

The illustrations in Gross’s papers on the conditions he named anomalous

origin of the innominate artery and anomalous origin of the left carotid artery
(1-3) show an anatomic pattern whereby the right and left common carotid
arteries both arise from a short “innominate” trunk, although how many of the
patients Gross accepted as having symptomatic tracheal compression by

We are indebted to Mrs. Peggy C . Earhart for preparation of the manuscript, to Dr. Howard Tucker,
Department of Mathematics, University of California at Irvine, for advice on conduct and interpretation of
the statistical procedures employed in this study, and to Ms. Patricia Kowal for preparation of Fig. 4.
Address reprint requests to Benjamin H. Landing, MD, Children’s Hospital Los Angeles, Depart-
ments of Pathology and Laboratory Medicine, Box 103, 4650 Sunset Blvd., Los Angeles, California 90027.

Pediatric Pathology, 13.203-212, 1993 203

Copyrkh! 0 1993 Tylor d Francis
0277-0938/93 $10.00 + . 00
 204 T. R. WELLS E l AL.

(6
anomalous innominate artery” had this anatomic pattern is not given in his
data. Poynter, in 1916, in his classical study of anatomic variations of the arter-
ies arising from the aortic arch, used the term “innominate trunk with the left
carotid artery springing from it” for the usual form of this anatomic variation
and the term “bicarotid trunk” for the rarer pattern of origin of both right and
left common carotid arteries from a short common trunk with the right subcla-
vian artery having more distal origin and retroesophageal course. Poynter ex-
plained the lack of specific mention of the anatomic pattern in anatomy texts by
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the fact that “Older anatomists considered the pattern normal’’ (4). Although
intended as a description rather than as the name of the pattern, the term
“common origin of the innominate and left carotid arteries” may first have
been used by Williams and Edmonds in 1935 (5). The present edition of the
Birth Defects Encyclopedia (6) lists the more usual form of common origin of
the carotid arteries (COCA) as “artery, brachiocephalic and contralateral ca-
rotid, common origin” (entry 0200, p. 186), with the notation “Associated
findings: none known,’’ and presents COCA as the anatomic basis of the condi-
tion usually called, in the more recent surgical literature, anomalous origin of
the innominate artery. Because increased frequency of COCA in patients with
For personal use only.

origin of the left coronary artery from the pulmonary artery, esophageal atresia-
tracheoesophageal fistula, or DiGeorge anomaly has been proposed (7-9), the
present study of the incidence of COCA in a number of other cardiovascular
and other anomaly situations was performed.
The major source of material for the present study was a series of speci-
mens from patients with congenital cardiovascular anomalies, so possible syn-
dromal associations of COCA with conditions of other types, such as midline
field defects not associated with cardiac malformation, are not addressed in
this study.

MATERIALS AND METHODS

Evaluation of the great vessels arising from the aorta for COCA, defined
as the presence of an arterial trunk giving rise to both the right and left
common carotid arteries, with or without independent origin of the right sub-
clavian artery from the aorta, was done for 122 neonates, infants, and chil-
dren, with age range 25 weeks of gestation to 9 years, from heart-lung speci-
mens in the Gabriel C. Duque Jr. Memorial Cardiac Registry of the
Department of Pathology and Laboratory Medicine, Childrens Hospital Los
Angeles. The categories analyzed in this study included truncus arteriosus,
aorticopulmonary window, congenital polyvalvular disease, tetralogy of Fallot
not associated with DiGeorge anomaly, pentalogy of Cantrell, clinical Noonan
phenotype, 13, 18 and 21 trisomies for patients who also had other cardiovas-
cular anomalies, and acrocephalosyndactyly syndromes. Included in the sta-
 COMMON ORIGIN OF CAROTID ARTERIES 206

tistical analyses carried out on the material of the present study were the data
of Landing et al. (8) on COCA in patients with esophageal atresia/
tracheoesophageal fistula, of Ehren et al. (7) on COCA in patients with anom-
alous origin of the left coronary artery from the pulmonary artery, and of Sein
et al. (9) on COCA in patients with DiGeorge anomaly, for a total of 140
patients in the analyses. Specimens from 20 patients who had normal hearts
and none of the syndromes listed above were studied as controls. Figure 1
shows the stage of development of the derivatives of the embryonic ventral
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aorta, the persistence of which gives the vascular pattern called COCA.
Values of the observed associations of COCA with the conditions listed
above are given in Table 1. Figures 2 and 3 show the relations of the carotid
arteries in the most frequent pattern of COCA, with the short trunk leading to
both common carotid arteries and the right subclavian artery.
Statistical analyses of the significance of the observed numbers of patients
with and without COCA in the disease categories studied were done by the
method of normal approximation to the hypergeometric distribution (lo), us-
ing a calculated value of 13% incidence of COCA in the general population
from which the patients in the study were drawn (estimated 11% incidence of
For personal use only.

COCA in whites and 20% in blacks). The results of this analysis are shown in

FIGURE 1. Diagram of great vessel pattern at the embryologic stage at which both common carotic
arteries arise from a common vascular trunk. The diagram shows the form of common origin of the carotid
arteries (COCA) called by Poynter (4) “innominate stem with the left carotid springing from i t ” ; a similar
relation of both common carotid arteries, with anomalous origin of the right (or very rarely the left)
subclavian artery, was called by Poynter “bicarotid trunk.’’ Both these categories are included in the
concept COCA in the present study. Reprinted with permission from Ehren et al. (7).
 206 T. R. WELLS ET AL.

TABLE 1. Observed Incidences of COCA in Disease Categories Analyzed in the Present Study'

Observed incidence
Category of COCA

Controls, no cardiac malformation 2/20 (10%)

Esophageal atresia with tracheoesophageal fistula (EA/TEF) 8/17 (47%)
Anomalous origin of left coronary artery from
pulmonary artery (ALCAPA) 11/13 (85%)
DiGeorge anomaly (DGA) 10119 (53%)
Tetralogy of Fallot not associated with DGA (TOF not DGA) 4/11 (36%)
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Acrocephalosyndactyly syndromes (Apert syndrome, 3; Carpenter

syndrome, 1 ; acrocephalospondylosyndactylysyndrome, 1) (ACSS) 4/51 (80%)
Clinical Noonan phenotype (CNP) 4/6 (67%)
Truncus arteriosus (TA) 4/5 (80%)
Aorticopulmonary window (APW) 3/6 (50%)
Congenital polyvalvular disease (CPD) 7/9 (78%)
Trisomy 13 (TS13) 7/11 (64%)
Trisomy 18 (TS18) 12/23 (52%)
Trisomy 21 (TS21) 8/19 (42%)
Pentalogy of Cantrell (POC) 0/7 (0%)

"Patients falling in more than one category were included in all appropriate categories (two patients had
For personal use only.

CPD, CNP, and COCA; two had EA/TEF, TS18, and COCA; one had DGA, CNP, and COCA; one had
DGA and TA but not COCA; and one had E N T E F and TS18 but not COCA).

Fig. 4 and Tables 2 and 3. Use of the values 1 7 % in whites and 42% in
blacks, the highest reported values we have found (5), corresponding to values
of 18% COCA and 82% not COCA, in the general population, does not
change the statistical significance of the relations described. The incidence of
COCA in the general population would have to be 21 % or greater for the
least abnormal ratio, that for tetralogy of Fallot, to lose significance at the 5%
level.

RESULTS

Table 1 gives the incidences of COCA for the categories of disease studied.
The highest observed association with COCA in these data was with anoma-
lous origin of the left coronary artery from the pulmonary artery (ALCAPA)
(85%) (7), but 80% of patients with truncus arteriosus or with a
craniosynostosis-syndactyly syndrome had COCA, as did 78 76 of patients
with congenital polyvalvular disease, 67 76 of patients with clinical Noonan
phenotype, 53 % of patients with DiGeorge anomaly (DGA), 50 % of patients
with aorticopulmonary window, 47 % of patients with esophageal atresia-
tracheoesophageal fistula, and 36% of patients with tetralogy of Fallot who
did not also have DGA. None of seven patients with pentalogy of Cantrell
 with POC who were also studied (data not included in Table 1).
Statistical analysis showed that all categories of patients analyzed had a
significantly greater incidence of COCA than the general population except
pentalogy of Cantrell, with the order of significance as follows: T O F not
DGA; AP window; clinical Noonan phenotype; acrocephalosyndactyly syn-
dromes, specifically Apert syndrome; truncus arteriosus; trisomy 2 1; esopha-
geal atresia-tracheoesophageal fistula; trisomy 13; DGA; congenital poly-
valvular disease; trisomy 18; and ALCAPA. There was no difference in the
incidence of COCA by sex.

DISCUSSION
As stated above, the anatomic arterial pattern, common origin of carotid
arteries (COCA) has been proposed as the general explanation of the terms
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For personal use only.

FIGURE 2. Aortic arch of 2-day-old male with congenital polyvalvular disease and COCA. The short
common trunk, giving rise to (in order from left to right in the figure) the right subclavian artery, the right
common carotid artery, and the left common carotid artery, is well shown. The figure also demonstrates
that in this more common form of COCA the aortic arch has only two large ostia, one for the innominate-
left carotid trunk and one for the left subclavian artery, in contrast to the usual three. In the less frequent
form of COCA with bicarotid trunk, left aortic arch, and anomalous origin of the right subclavian artery
and in the rare form with bicarotid trunk, right aortic arch, and anomalous origin of the left subclavian
artery, the third major ostium is more distally situated than is normal.
 208 T. R. WELLS ET AL.
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FIGURE 3. Aortagram of 5-month-old male with anomalous origin of the left coronary artery from the
pulmonary artery, showing the short common trunk giving rise to both the innominate artery and the left
common carotid artery.
For personal use only.

anomalous origin of the innominate artery and anomalous origin of the left
carotid artery.
That some patients with COCA are symptomatic, while others are not,
remains inadequately explained. Respiratory distress in the neonate with
COCA has been attributed to superior mediastinal crowding, and the fre-
quent improvement of symptoms with age to lessening of the degree of such
crowding (11). Gross (3) suggested that when the “anomalous vessel” com-
pressing the trachea was lax there were no symptoms, and conversely, that
when the vessel was tight the patient was symptomatic. That the difference
between patients with symptomatic versus asymptomatic COCA might be due
to different degrees of intrinsic tracheal cartilage softness (tracheomalacia in
the strict sense) has also been suggested (1 1). To our knowledge, no evidence
has been provided that any of these explanations is correct. Interesting in this
regard are reports of patients with esophageal atresia and tracheoesophageal
fistula who were initially asymptomatic but later developed stridor caused by
tracheal compression by COCA (12).
The study of Takahashi (13), utilizing angiographic demonstration of the
site of origin of the innominate artery along the aortic arch, showed no signifi-
cant relation of the incidence of clinical tracheal compression to the site of
origin of the artery, possibly because of the small size of the series. Although
the differences were not statistically significant, Takahashi’s data do show the
highest proportion of symptomatic tracheal stenosis for patients with origin of
the innominate trunk farthest to the left along the aortic arch and are in
 COMMON ORIGIN OF CAROTID ARTERIES 209

04

0 35

03

D 025
n
-
02 TA h ACSS

-n-
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P
? 015

01

0 05

ALCAPA ,;,, z.score

FIGURE 4. Graph showing distribution of probabilities that the observed numbers of patients with and
For personal use only.

without COCA in the disease categories sampled differ significantly from the ratio 13% with COCA and
87 % without COCA, calculated using the normal approximation of the hypergeometric distribution. The
graph shows that all the disease categories studied show significantly increased incidence of COCA except
pentalogy of Cantrell. The ordinate of the graph shows Z-scores (standard scores) corresponding to posi-
tions of various possible sample ratios along the distribution curve, and the abscissa shows the probabilities
of significant difference from chance for the disease category samples studied. The precise values for the
probabilities of difference from chance for the categories studied are listed in a footnote to Table 2.

accord with earlier data (14) suggesting that the longer course of the innomi-
nate or right common carotid artery over the anterior surface of the trachea
with leftward origin of either vessel causes a greater degree of tracheal com-
pression.
Because of the nature of the data base used in the present study, the
proportions of patients in the various anomaly categories analyzed who may
have had clinical features of tracheal compression due to COCA cannot be
given. Appropriate clinical studies on patients in the groups with the most
convincing increase in incidence of COCA-anomalous origin of the left coro-
nary artery from the pulmonary artery, DiGeorge anomaly, esophageal
atresia-tracheoesophageal fistula, trisomies 13, 18, and 21, truncus arte-
riosus, and congenital polyvalvular disease-would be of interest and would
perhaps shed light on why some patients with COCA have symptomatic tra-
cheal compression while the majority do not. Of the five patients in the study
who had an acrocephalosyndactyly syndrome, three with Apert syndrome and
one with Carpenter syndrome had COCA and one with acrocephalospondylo-
syndactyly syndrome did not. The association with COCA is statistically sig-
 Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of Auckland on 11/04/14
For personal use only.

TABLE 2 . Probabilities of Significant Difference from the General Population of Observed Numbers of Patients with and without COCA in a Series with a
Specific Disease Category"
~

Number Number without COCA

with
COCA 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

0 xxxx 0.86 0.69 0.57 0.49 0.42 0.36 0.32 0.28 0.24 0.22 0.19 0.17 0.15 0.13 0.12
1 0.14 0.31 0.42 0.51 0.58 0.64 0.68 0.72 0.63 0.57 0.53 0.48 0.43 0.39 0.36 0.32
2 0.005 0.03 0.07 0.12 0.19 0.25 0.31 0.37 0.42 0.48 0.48 0.57 0.61 0.64 0.63 0.59
3 0.0001 0.001 0.006 0.02 0.03 0.06 0.09 0.12 0.16 0.19 0.24 0.26 0.32 0.37 0.41 0.45
4 0.0001 0.0003 0.001 0.004 0.008 0.02 0.025 0.04 0.06 0.06 0.1 0.13 0.15 0.19 0.22
5 * * 0.0001 0.0003 0.0008 0.002 0.004 0.007 0.01 0.02 0.03 0.04 0.05 0.06 0.08
t *
6 0.0001 0.0002 0.0004 0.0009 0.002 0.003 0.005 0.008 0.01 0.02 0.02
7 * * 0.0001 0.0002 0.0004 0.0007 0.001 0.002 0.003 0.005
I * t t *
8 0.0001 0.0002 0.0003 0.0005 0.0006
9 * * * * . * * * 0.0001 0.0001
* t * * * I t * *
10
* * * I * * * * *
11
12 * * * * * *
* * * * * * t * * * * t I
13
I * I * t
14
* t * * t * * t *
15

"The table can be used to establish the probabilities that observed numbers of patients with and without COCA differ from the base population, for any other
disease category not known to have differential racial distribution, up to an N of 15 for the larger value (number of patients with or number of patients without
COCA). The table is based on the ratio of patients with and without COCA in the population studied of 13% to 87%. The specific probabilities corresponding to
the ratios observed in the 13 disease categories analyzed in the present study are listed in Table 3.
*p c 1 x lo+.
 COMMON ORIGIN OF CAROTID ARTERIES 21 1

TABLE 3. Specific Probabilities in the 13 Disease Categories Analyzed

~

No. of No. No.

specimens with without
studied COCA COCA Disease category P
7 0 7 Pentalogy of Cantrell 0.32
11 4 7 Tetralogy of Fallot, not DGA 0.025
6 3 3 Aorticopulmonary window 0.02
6 4 2 Clinical Noonan phenotype 0.003
5 4 1 Acrocephalosyndactyly syndromes 0.0001
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5 4 1 Truncus arteriosus 0.0001

19 8 11 Trisomy 21 0.0001
17 8 9 Esophageal atresia-
tracheoesophageal fistula <0.00001
11 7 4 Trisomy 13 < 0.0000 1
19 10 9 DiGeorge anomaly (DGA) < 0.0000 1
9 7 2 Congenital polyvalvular disease < 0.0000 1
23 12 11 Trisomy 18 < 0.0000 1
13 11 2 Anomalous left coronary artery
from pulmonary artery (ALCAPA) < 0.00001
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nificant for Apert syndrome, but further study of these relations would be
useful, since tracheal cartilaginous sleeve malformation (tracheal splint) is also
associated with this group of syndromes (15).
Because the autopsy service from which the material of this study was
drawn has not regularly kept specimens of heart plus aorta and great arteries
for patients not diagnosed at the time of autopsy as having cardiovascular
anomaly, and because COCA is relatively rarely recognized at autopsy, analy-
sis of the incidence of COCA in other disease categories of interest, such as
midline field problems (e.g., Beckwith and other hemihypertrophy-
hemiatrophy syndromes, coloboma-heart disease-choanal atresia-genital
hypoplasia-ear anomolies (CHARGE) association, etc.), is not possible from
the data base used for the present study. Table 2 is presented in part as an aid
to other workers who may wish to investigate such relations.

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For personal use only.

Received March 10, 1992

Accepted June 20, 1992