Anatomy in Patients with 22q11 Deletion and Pulmonary Atresia with Ventricular Septal Defect and Major Aortopulmonary Collaterals

doi:10.4236/ss.2011.25063

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Surgical Science, 2011, 2, 294-296

doi:10.4236/ss.2011.25063 Published Online July 2011 (http://www.SciRP.org/journal/ss)

Anatomy in Patients with 22q11 Deletion and Pulmonary

Atresia with Ventricular Septal Defect and Major

Aortopulmonary Collaterals

Ashish O. Sureka1, Lynn F. Peng2, Olaf Reinhartz2, V. Mohan Reddy2, Frank L. Hanley2

1Pediatrix Cardiology of North Texas, Dallas, USA

2Lucille Packard Children’s Hospital, Palo Alto, USA

E-mail: [email protected]

Received April 30, 2011; revised June 20, 2011; accepted July 6, 2011

Abstracts

We performed a retrospective analysis of patients with and without 22q11 deletion undergoing surgery for

pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals between January 2004

and August 2009 at our institutions. Information was collected on collateral origin, arch sidedness, presence

of central pulmonary arteries, and presence of an aberrant subclavian vessel. While patients with 22q11 dele-

tion were more likely to have collateral origin from brachiocephalic vessels, patients without 22q11 deletion

were more likely to have collateral origin from the descending aorta. There was no significant difference in

arch sidedness or the presence of central pulmonary arteries. Patients with 22q11 deletion were more likely

to have an aberrant subclavian artery (15/46 vs 5/54, p < 0.05), whether a left or right arch was present. Nine

of the fifteen 22q11 deletion patients had a collateral originating from an aberrant subclavian artery. In time,

genomic and embryologic research may help determine the exact mechanisms by which 22q11 deletion con-

tributes to the development of congenital heart disease such as pulmonary atresia with ventricular septal de-

fect and major aortopulmonary collaterals.

Keywords: Tetralogy of Fallot with Pulmonary Atresia, Pulmonary Atresia with Ventricular Septal Defect,

22q11 Deletion

1. Introduction

The disease spectrum known as 22q11 deletion syndrome

is associated with cardiac, immunologic and psychiatric

abnormalities. Although the exact mechanism of the de-

letion’s effect is unknown, abnormal neural crest cell mi-

gration seems to contribute [1]. The T-Box 1(TBX1) ge-

netic pathway appears to be involved in the formation of

the pharyngeal arches and the cardiac outflow tracts [2,3].

Mice heterozygous for the TBX1 deletion have a high

frequency of defects of the fourth aortic arch [1,4]. In

addition, haploinsufficiency of TBX1 appears to cause

poor development of the distal outflow tracts [5-9].

A particularly challenging lesion common in these pa-

tients is pulmonary atresia with ventricular septal defect

with major aortopulmonary collaterals (PA/VSD/ MAP-

CA’s), also known as tetralogy of Fallo t with pulmonary

atresia and major aortopulmonary collaterals. Among

patients with this lesion, several studies have attempted

to highlight the differences between the patients with and

without 22q11 deletion. In one study comparing 23 cases

to controls, patien ts with the deletion were more likely to

have a right aortic arch, aberrant subclavian artery, and

MAPCA’s than patients without the deletion. There was

no difference in the incidence of absent true confluent

central pulmonary arteries [10].

A prospective study describing 25 patients compared

to controls foun d tho se with PA/VSD and 22 q11 de letion

were more likely to have MAPCA’s and absen t conflu en t

central pulmonary arteries than those without the dele-

tion. There was no difference in the incidence of an ab-

errant subclavian artery. Among the 25 patients, ten had

MAPCA’s, all originating from the descending aorta

[11].

This study sought to examine the comparative anat-

omy in patients with pulmonary atresia with ventricular

septal defect with major aortopulmonary collaterals with

and without 22q11 deletion.

A. O. SUREKA ET AL.295

2. Materials and Methods

We reviewed the data for all patients with PA/VSD/ MA-

PCA’s who underwent surgery at our institutions be-

tween January 2004 and August 2009. All patients un-

derwent cardiac catheterization and echocardiogram be-

fore operation; in some cases, the catheterization was

performed at outside institutions. All angiograms were

reviewed by the investigators at our institution. All cathe-

terizations were performed systematically to establish the

following information:

a) collateral origin(s), whether from brachiocephalic

arterial vessels, ductus-like collatera l vessels, descend-

ing aorta, or coronary arteries (patients often have mul-

tiple collaterals from various origins)

b) presence of central pulmonary arteries

c) arch sidedness

d) presence of an aberrant subclavian artery

Patients without selective angiograms that adequately

defined collateral origin or arch sidedness were excluded

from the study. Collaterals originating from the under-

surfac e of the aor ta but not en circ led by the r ecurren t lar-

yngeal nerve were termed ‘ductus-like collateral vessels,’

while other collaterals originated from brachiocephalic

arteries, the descending aorta, or coronary arteries.

All patients underwent FISH testing for 22q11 dele-

tion. Many patients were referred; the method of 22q11

flourescent in situ hybridization (FISH) testing v aried by

referring institution.

Statistical analysis was performed by Fisher’s exact

test. Analysis was performed with SAS version 9.1 (SAS

Institutes Inc., Cary, NC). Significance was determined

at a p value of less than 0.05. All p values were two-

tailed.

3. Results

Table 1 outlines the anatomical differences of PA/VSD

/MAPCA’s patients with 22q11 deletion compared to the

patients without the deletion. Patients with 22q11 dele-

tion were significantly more likely to have an aberrant

subclavian artery, regardless of arch sidedness (p < 0.05).

Among the 15 patients with an aberrant subclavian artery,

6 had a left aortic arch with an aberrant right subclavian

artery, while 9 had a right aortic arch with an aberrant

left subclavian artery. Nine of the 15 patients with an ab-

errant subclavian artery (60%) had a collateral originat-

ing from that vessel.

Patients with 22q11 deletion were significantly more

likely to have a collateral vessel arise from a brachioce-

phalic artery (p < 0.01). Patients without 22q11 deletion

were more likely to have a collateral vessel arising from

the descending aorta (p < 0.05).

Table 1. Anatomical differences in PA/VSD/MAPCA’s pa-

tients with and without 22q11 deletion.

Characteristic 22q11 Positive 22q11 Negativep-value

Brachiocephalic

artery collateral

vessels 25 of 46 (54%) 13 of 54 (24%)0.035*

Ductus—like

collateral vessels 7 of 46 (15%) 2 of 54 (4%) 0.076

Descending aorta

collateral vessels 40 of 46 (87%) 53 of 54 (98%)0.046*

Coronary arter y

collateral vessels 2 of 46 (4%) 4 of 54 (7%) 0.68

Presence of central

pulmonary a rteries35 of 46 (76%) 45 of 54 (83%)0.45

Presence of right

aortic arch 20 of 46 (43%) 21 of 54 (39%)0.69

Presence of aberrant

subclavian artery 15 of 46 (33%) 5 of 54 (9%) 0.0052*

*= p value < 0.05.

4. Discussion

To our knowledge, this is the first report detailing the

origin of collateral vessels in PA/VSD/MAPCA’s with

and without 22q11 deletion. As in previous reports, 22q11

deletion was associated with an aberrant subclavian ar-

tery [12,13]. Notably, in our study the presence of the

22q11 deletion was not significantly p r edictiv e for a right

aortic arch among patients with PA/VSD/ MAPCA’s.

These findings could help guide diagnostic testing in

patients with PA/VSD/MAPCA’s, with and without

22q11 deletion. Testing for sources of collateral circula-

tion is generally not methodical—the aorta, coronary art-

eries, and brachiocephalic vessels are assessed by cathe-

terization. In the era of widespread availability of FISH

testing, we believe our findings may help direct assess-

ment for collaterals and abnormalities of vessel branch-

ing based on the patient’s 22q11 status. Patients with

22q11 deletion are more likely to have collaterals from

brachiocephalic vessels and an aberrant subclavian artery,

regardless of arch sidedness.

The results of this study may also have long-term im-

plications for determining the mechanism by which 22q11

deletion interferes with the normal development of the

cardiac outflow tracts. Though abnormal migration of

neural crest-derived tissues has been implicated, it is un-

clear why and how patients with the deletion would more

often develop collateral circulation from brachiocephalic

vessels. More precise molecular characterization could

be helpful.

This study had several limitations. Referral bias was a

significant concern. As our institution is a referral center

for PA/VSD/MAPCA’s, our patients may not have

A. O. SUREKA ET AL.

296

anatomy representative of the entire population of PA/

VSD/MAPCA’s patients, with and without 22q11 dele-

tion. Also, the fact that some of the patients had studies

(including the FISH test and catheterization) at various

institutions introduces bias.

Collaterals can regress over time, and these patients

entered our system at various ages. A cohort study of all

newborns may yield different results.

Studies with more PA/VSD/MAPCA’s patients would

be helpful to better characterize the anatomy in those

with and without 22q11 deletion. In time, genomic and

embryologic research may help determine the exact me-

chanisms by which 22q11 deletion contributes to the

development of congenital heart disease such as PA/VSD

/MAPCA’s.

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