Case 28
Interrupted Aortic Arch in a Patient
with DiGeorge Syndrome
Sabrina D. Phillips
Age: 18
Gender: Female
Occupation: Student
Working diagnosis: Left ventricular outflow tract obstruction and DiGeorge syndrome
HISTORY
The patient was the product of a normal pregnancy delivered
at term. She initially had symptoms of heart failure on day 10
of life. She was found to have nearly complete aortic arch
interruption, a VSD, and an ASD. Before a planned operative
repair, she was noted to have hypocalcemia, which was cor-
rected. Otherwise, she underwent repair of the aortic arch, VSD
closure, and ASD closure and had no operative complications.
Thereafter, she grew normally.
At 10 years of age the patient again developed heart failure
symptoms. She was diagnosed with severe aortic valve stenosis,
and a balloon valvotomy was attempted. During that hospital-
ization, however, she developed a severe systemic infection
with severe splenomegaly and hepatomegaly. This was eventu-
ally diagnosed as a cytomegalovirus infection. Her aortic steno-
sis was not relieved after the balloon valvotomy, so she was
considered for operative replacement of her aortic valve. She
developed a transfusion reaction during a platelet transfusion
that was being administered prophylactically for thrombocyto-
penia prior to a diagnostic angiogram. The patient eventually
had replacement of her aortic valve with a 21-mm St. Jude
prosthesis. Notably, several large mediastinal lymph nodes
were removed during this surgery.
The patient did well initially after her aortic valve replace-
ment, and cardiology follow-up visits were unremarkable. She
was eventually diagnosed with selective IgA deficiency and
treatment was initiated with monthly IVIG infusion. In late
adolescence, however, she began to feel increasingly tired. She
presented at 18 years of age with increasing fatigue and reduced
exercise tolerance over the prior 6 months.
C o m m e n t s : Cardiac anomalies commonly associated with
DiGeorge syndrome include tetralogy of Fallot, pulmonary
atresia/VSD, truncus arteriosus, and interrupted aortic arch.1
Hypocalcemia in DiGeorge syndrome occurs secondary to
absent parathyroid function. The term partial DiGeorge syndrome
is applied when infants have impaired rather than absent para-
thyroid or thymus function,2 as in this case.
Patients with DiGeorge syndrome manifest a deficiency in
cell-mediated immunity related to thymic hypoplasia. Suscep-
tibility to infection is variable.2 Disorders of humoral immunity
can also occur.3
Some patients with DiGeorge syndrome produce autoanti-
bodies to red cells, white cells, and platelets.2
Fatigue is a very nonspecific symptom at any age, and late
adolescence can cause psychosocial problems that can be diffi-
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cult to decipher against the background of complex congenital
heart disease. Further, DiGeorge patients are at risk for depres-
sion and schizophrenia.4 Still, a hemodynamic cause of deterio-
ration must be sought.
CURRENT SYMPTOMS
The patient had exertional fatigue. She denied dyspnea, orthop-
nea, and paroxysmal nocturnal dyspnea. She did not have intol-
erance to heat or cold, or constipation. Her menstrual cycles
were regular but generally heavy. She noted that it had been
very difficult to keep her INR in the therapeutic range. She also
admitted that she was ambivalent about anticoagulation, as she
was prohibited from some activities because of fear of injury
and bleeding.
NYHA class: I–II
C o m m e n t s : There were no typical symptoms of thyroid
disease to explain her fatigue, but thyroid disease should be
properly excluded by laboratory testing. Heavy menses may be
associated with iron deficiency anemia, which may cause fatigue
or exacerbate cardiac causes of fatigue. Selective IgA deficiency
is associated with malabsorption and is another potential cause
of iron deficiency anemia.5 Malabsorption likely contributes to
difficulty in controlling oral anticoagulation and results in a
need for higher warfarin doses. Noncompliance certainly needs
to be considered, especially in teenagers and young adults with
chronic disease who may rebel against the constraints placed
on them. Compliance could be increased with home INR mon-
itoring and education.
CURRENT MEDICATIONS
Trimethoprim/sulfamethoxazole, regular strength, orally twice
daily
IVIG Polygam, every 5 weeks
Hydrocortisone prior to IVIG administration
Coumadin 9.5 mg daily (target INR 2.5–3.5)
Subacute bacterial endocarditis prophylaxis
C o m m e n t s : Trimethoprim/sulfamethoxazole is admin-
istered prophylactically in this patient secondary to her reduced
CD4 cell count. IVIG and steroids are useful in the treatment of
autoantibodies to red cells, white cells, and platelets. This also
Cases in Adult Congenital Heart Disease  157
 provides treatment for deficiency of immunoglobulin, which C o m m e n t s : A mild pancytopenia is present, which may
this patient has demonstrated. be secondary to autoantibodies to red cells, white cells, and
Left-Sided Lesions / Coarctation of the Aorta

platelets. Iron deficiency is possible given the microcytic picture.

The degree of anemia is unlikely to be the cause of her
PHYSICAL EXAMINATION fatigue.
BP 100/70 mm Hg (arm), 100/70 mm Hg (leg); HR 80 bpm;
oxygen saturation 100% Other Relevant Lab Results
2 TSH 4.0 mIU/L (0.3–5)
Height 151 cm, weight 39 kg, BSA 1.28 m
Bio-Intact PTH (1-84) <4.0 pg/mL (10–55)
Head and neck: Long, narrow face with a pointed chin, narrow Calcium 7.7 mg/dL (9.1–10.3)
palpebral fissures, and small ears with overfolding of the Albumin 4.6 g/dL (3.5–5.0)
superior helix INR 1.9
IgA 2 mg/dL (55–377)
Surgical scars: Sternotomy IgM 19 mg/dL (56–242)
Neck veins: Normal IgG 1310 mg/dL (724–1611)
Lungs/chest: Decreased air entry in the right lung base
C o m m e n t s : The low parathyroid hormone (PTH) and
Heart: There was a regular rhythm, a 2+ LV impulse, a crescendo- calcium are consistent with reduced parathyroid function.
decrescendo murmur heard best at the right upper sternal Her INR is low. One may need to ask her about and empha-
margin, a crisp, metallic A2, and a suprasternal thrill. The size compliance. She may need to reduce her dietary vitamin K
carotid upstroke was delayed. intake. The dose of warfarin needed to maintain an adequate
INR may be higher secondary to the malabsorption associated
Abdomen: Marked hepatosplenomegaly was present. with IgA deficiency.
Extremities: There was no radiofemoral delay; no cyanosis,
clubbing, or edema. The levels of IgA and IgM are severely reduced, consistent
with a defect in antibody-mediated immunity.
Pertinent Negatives
She was not pale. ELECTROCARDIOGRAM
C o m m e n t s : The patient’s height and weight are less than
the third percentile when plotted on standard growth curves. I aVR V1 V4
Patients with DiGeorge syndrome commonly have short stature.
This may be related to growth hormone deficiency or hypo­ II aVL V2 V5
thyroidism, both of which have been associated with the
syndrome.3 Poor growth is also seen in children with immuno-
globulin deficiency.6 III aVF V3 V6
Several “typical” facial features have been described in
patients with DiGeorge or velocardiofacial syndrome. These II
include a small mandible, long face, large nose, narrow palpe-
bral fissures, abnormal ear folding, and a flat malar region. V1
However, the features described are subtle, and two separate
studies have demonstrated an inability to predict whether a
patient has the syndrome based on facial features.1,7 V5
The cardiac exam is consistent with severe aortic valve steno- Figure 28-1  Electrocardiogram.
sis. There was no radiofemoral delay to suggest significant
coarctation. She did not appear anemic.
Findings
Heart rate: 74 bpm
LABORATORY DATA QRS axis: +109°
Hemoglobin 11.3 g/dL (11.5–15.0)
QRS duration: 138 msec
Hematocrit/PCV 33.8% (36–46)
MCV 73 fL (83–99) Normal sinus rhythm with a nonspecific intraventricular con-
Platelet count 106 × 109/L (150–400) duction delay and right-axis deviation.
Leukocyte count 2.0 × 109/L (3.5–10.5)
Sodium 139 mmol/L (134–145) C o m m e n t s : The patient does not have clear evidence of
Potassium 3.8 mmol/L (3.5–5.2) LV hypertrophy, which should be looked for in any patient with
Creatinine 0.7 mg/dL (0.6–1.2) aortic valve and/or arch stenosis.

158  Cases in Adult Congenital Heart Disease

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CHEST X-RAY
Figure 28-2  Posteroanterior projection.
Findings
Cardiothoracic ratio: 45%
Moderately dense infiltrates and pleural thickening around the
right lung base were seen, as well as increased pulmonary vas-
cularity. Epicardial leads and an aortic prosthesis were noted.
C o m m e n t s : Often, epicardial leads were placed by sur-
geons at the time of other surgery for potential future use.
Although the patient does not have a pacemaker, consideration
of these wires is relevant when considering the utility of a MRI
scan (see Fig. 28-6).
ECHOCARDIOGRAM
Figure 28-3  Parasternal long-axis view.
Findings
The LV was normal in size with normal systolic function, ejec-
tion fraction 62%. There was no LV hypertrophy. No evidence
of residual VSD or ASD was seen.
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In addition, mild RV enlargement with normal systolic
function was noted. The estimated RV systolic pressure was
Interrupted Aortic Arch in a Patient with DiGeorge Syndrome
32 mm Hg.
C o m m e n t s : LV hypertrophy would be expected in a
patient with significant prosthetic valve stenosis.
Figure 28-4  Continuous-wave Doppler of the aortic valve.
Findings
Severe aortic valve prosthetic stenosis was present. The peak
velocity was 4.7 m/sec, giving a systolic gradient of 88 mm Hg.
The mean systolic Doppler gradient was 49 mm Hg. There was
mild prosthetic regurgitation.
C o m m e n t s : Mechanical prosthetic aortic valve stenosis is
most commonly related to pannus formation or thrombosis.8–11
The incidence of pannus formation resulting in valve obstruc-
tion is estimated to be about 1% to 6%.12 Thrombosis must be
considered in this patient given the history of variable control
of her anticoagulation.
Figure 28-5  Suprasternal notch view of the aortic arch.
Findings
There was mild residual obstruction of the aortic arch just distal
to the origin of the left common carotid artery, with a maximal
instantaneous gradient of 21 mm Hg and a mean systolic gradi-
ent of 13 mm Hg.
C o m m e n t s : The patient was born with an interrupted
aortic arch, one of many congenital defects associated with
DiGeorge syndrome. The residual narrowing here is a known
long-term complication of the early repair.
Cases in Adult Congenital Heart Disease  159
 MAGNETIC RESONANCE
Left-Sided Lesions / Coarctation of the Aorta
ANGIOGRAPHY
Figure 28-6  Maximal intensity projection image of the aortic arch.
Findings
There was mild residual narrowing of the aortic arch. An aber-
rant right subclavian artery was seen originating distal to the
origin of the left subclavian artery. The course of the right sub-
clavian artery was posterior to the esophagus.
C o m m e n t s : Patients with type B aortic interruption and
patients with DiGeorge syndrome often have an aberrant right
subclavian artery related to the embryologic neural crest con-
tribution to the vascular anatomy.12
It should be noted that on the CXR the patient had epicardial
pacing leads, which were often left in place after cardiac surgery
and commonly found in adult congenital heart disease patients
even when no pacemaker is present. Such leads are considered
a possible contraindication to MRI because of the potential for
heating. However, more and more laboratories are challenging
this contraindication. Even if no appreciable heating occurs, the
wires can still cause significant artifacts. Thankfully, this angio-
gram was not affected by such artifact.
Focused Clinical Questions
and Discussion Points
1. What is the etiology of the DiGeorge phenotype?
DiGeorge syndrome is the result of a microdeletion of chromo-
some 22q11.2. It is part of a spectrum of phenotypic expression
of this deletion, which also includes velocardiofacial syndrome
and conotruncal anomaly face syndrome. These syndromes have
been referred to as CATCH-22 disorders (Cardiac defects,
Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypo-
calcemia) and result from developmental abnormalities of
the embryonic third and fourth branchial arches and neural crest
cells.3 The 22q11.2 microdeletion is the most common deletion
disorder in humans, with an incidence of approximately 1 out of
4000 births.13
160  Cases in Adult Congenital Heart Disease
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2. Do patients with 22q11.2 microdeletion and conotruncal
abnormalities have an unfavorable surgical outcome?
Patients with 22q11.2 microdeletion tend to have more complex
pulmonary anatomy and abnormalities of great artery anatomy
when compared to patients with the same cardiac diagnosis who
do not have the microdeletion. This potentially affects surgical
outcome in an unfavorable manner.1 The multisystem conse-
quences of the microdeletion require a team approach to the
surgical patient, including anesthesia, hematology, and infec-
tious disease experts. Blood products should be irradiated in
patients with the DiGeorge phenotype to reduce transfusion-
related complications.2 Laryngotracheal abnormalities are com­­
mon and need to be anticipated by the anesthesiologist.
3. When should the 22q11.2 microdeletion be suspected?
Patients with conotruncal abnormalities (tetralogy of Fallot, pul-
monary atresia/VSD, truncus arteriosus, and interrupted aortic
arch) should be suspect, especially when there is an associated
right-sided aortic arch, discontinuous or hypoplastic pulmonary
arteries, multiple aortopulmonary collateral arteries, a dysplastic
or absent semilunar valve, or interrupted aortic arch type B.3
Aortic arch interruptions are defined as type A, B, or C depending
on the site of discontinuity of the aorta. Type A interruptions
occur distal to the left subclavian artery. Type B interruptions are
located between the left carotid artery and the left subclavian
artery. Type C interruptions are defined as aortic interruptions
between the right innominate artery and the left carotid artery.
The aorta and its branches distal to the interruption are supplied
by a patent ductus arteriosus.
Genetic testing can be performed via several methods to detect
the microdeletion. This testing is performed on peripheral blood
samples from the patient, from which lymphocytes are isolated.
DNA obtained from these lymphocytes is used in the testing.
Fluorescence in situ hybridization with commercial probes is
widely used. A multiplex ligation dependent probe amplification
single tube assay can also be used. This assay is rapid and eco-
nomical. Short tandem repeat segregation tests can also be used.13
Patients with the deletion should be counseled regarding preg-
nancy, as each offspring will have a 50% chance of having the
deletion themselves. Although genetic screening of parents of
index cases is recommended, most new presentations of DiGeorge
syndrome are sporadic.
4. Why did the St. Jude prosthetic valve become obstructed?
The pathogenesis of obstruction of a St. Jude medical aortic valve
prosthesis has been evaluated by several authors.8–11,14 While
thrombosis is often considered the culprit, pannus formation,
with or without thrombosis, has been documented at operation
more frequently.8,10 Thrombosis of a mechanical prosthesis tends
to occur earlier after implantation and at random, whereas
pannus formation requires a larger time interval after implanta-
tion and has a delayed exponential increase in risk.8 Thrombosis
of the prosthesis is more likely to present with acute symptoms
in contrast to pannus formation, which presents with increasing
valve gradient over time.8,10 The clinical distinction between
pannus and thrombosis, however, is quite difficult. This patient
presents with significant obstruction and a history of inadequate
anticoagulation, which makes thrombosis a concern. Operation
is indicated for relief of the obstruction, at which time the patho-
genesis can be determined. Thrombolytic therapy is not indicated
in this circumstance, as the patient is hemodynamically stable
and the true cause of obstruction is unknown.
FINAL DIAGNOSIS
DiGeorge syndrome
Severe prosthetic aortic valve stenosis
Mild aortic arch stenosis (following repair of aortic interruption
in infancy)
PLAN OF ACTION
Aortic valve re-replacement with multidisciplinary involve-
ment from hematology, anesthesiology, infectious disease,
and endocrinology
INTERVENTION
The patient underwent aortic valve re-replacement. The surgeon
described circumferential subvalvular obstruction of the pros-
thesis by fibrous tissue, which was confirmed by pathology to
be pannus formation without thrombosis. Dacron patch enlarge-
ment of the aortic valve annulus and implantation of a 19-mm
St. Jude aortic valve prosthesis was performed.
Pannus formation is likely caused by persistent neointimal
development related to a chronic inflammatory response that
results in proliferation of myofibroblasts and extracellular
matrix without fresh thrombus formation.9 Pannus is often
found to be circumferential and is almost exclusively found on
the LV aspect of the valve.9,10,14 The fibrous tissue most com-
monly restricts movement of the leaflets directly, but has been
demonstrated at a distance from the valve, resulting in LVOT
narrowing.14 The cause of leaflet motion restriction in the St.
Jude medical prosthesis may relate to its low-profile structure
and the placement of the pivot guards. The straight edges of the
leaflets are very close to the edge of the pivot guards in the fully
open position. One of the pivot guards comes into contact with
the ventricular wall (in either placement orientation). If pannus
formation occurs, growth into the pivot guards restricts the
opening of the leaflet without restricting closing of the
leaflet.10
A 19-mm prosthesis was chosen as this was the largest pros-
thesis that could be implanted after Dacron patch enlargement
of the aortic annulus. While this is a small prosthesis it was felt
to be adequate for this small patient, as she has completed
growth and has a BSA of only 1.28 m2.
OUTCOME
The patient’s postoperative course was complicated by AV dis-
sociation and heart failure. Hypocalcemia was noted, but cor-
rection of the hypocalcemia did not resolve the conduction
system abnormalities. Permanent pacemaker implantation was
performed.
Seven months after surgery, the patient presented with bac-
teremia and concerns for endocarditis. Serial transesophageal
echocardiography revealed a normal aortic valve prosthesis.
The patient had no further positive blood cultures after treat-
ment with a 4-week course of intravenous antibiotics.
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Conduction abnormalities requiring permanent pacemaker
implantation after aortic valve replacement have an incidence
Interrupted Aortic Arch in a Patient with DiGeorge Syndrome
of 5.7% but are not related to adverse long-term outcome when
compared to patients with aortic valve replacement who did
not need permanent pacing.15
Selected References
1. Beauchesne LM, Warnes CA, Connolly HM, et al: Prevalence and
clinical manifestations of 22q11.2 microdeletion in adults with
selected conotruncal anomalies. J Am Coll Cardiol 45:595–598,
2005.
2. Hayward AR: Immunodeficiency. In Hay WW, Hayward AR,
Levin M, Sondheimer JM (eds): Current Pediatric Diagnosis and
Treatment, 16th ed. New York, McGraw-Hill Professional, 2003,
pp 921–936.
3. Cuneo BF: 22q11.2 deletion syndrome: DiGeorge, velocardiofa-
cial, and conotruncal anomaly face syndromes. Curr Opin Pediatr
13:465–472, 2001.
4. Bassett AS, Chow EWC, Husted J, et al: Clinical features of 78
adults with 22q11 deletion syndrome. Am J Med Genet 138:
307–313, 2005.
5. Spickett GP, Misbah SA, Chapel HM: Primary antibody defi-
ciency in adults. Lancet 337:281–284, 1991.
6. Bjorkander J, Bake B, Hanson LA: Primary hypogammaglobu-
linaemia, impaired lung function, and body growth with delayed
treatment and inadequate treatment. Eur J Respir Dis 65:529–536,
1984.
7. Becker DB, Pilgram T, Marty-Grames L, et al: Accuracy in identi-
fication of patients with 22q11.2 deletion by likely care providers
using facial photographs. Plast Reconstr Surg 114:1367–1372,
2004.
8. Rizzoli G, Guglielmi C, Toscano G, et al: Reoperations for acute
prosthetic thrombosis and pannus: An assessment of rates, rela-
tionship and risk. Eur J Cardio-Thor Surg 16:74–80, 1999.
9. Teshima H, Hayashida N, Yano H, et al: Obstruction of St. Jude
medical valves in the aortic position: Histology and immunohis-
tochemistry of pannus. J Thorac Cardiovasc Surg 126:401–407, 2003.
10. Aoyagi S, Nishimi M, Tayama E, et al: Obstruction of St. Jude
medical valves in the aortic position: A consideration for patho-
genic mechanism of prosthetic valve obstruction. Cardiovasc Surg
10:339–344, 2002.
11. Katircioglu SF, Ulus AT, Yamak B, et al: Acute mechanical valve
thrombosis of the St. Jude medical prosthesis. J Card Surg 14:
164–168, 1999.
12. Bergwerff M, Verberne ME, DeRuiter MC, et al. Neural crest cell
contribution to the developing circulatory system: Implications
for vascular morphology? Circ Res 82:221–231, 1998.
13. Fernandez L, Lapunzina P, Arjona D, et al: Comparative study of
three diagnostic approaches (FISH, STRs and MLPA) in 30 patients
with 22q11.2 deletion syndrome. Clin Genet 69:373–378, 2005.
14. Kuniyoshi Y, Koja K, Miyagi K, et al: Pannus formation in aortic
valve prostheses in the late postoperative period. J Artificial
Organs 6:179–182, 2003.
15. Boughaleb D, Mansourati J, Genet L, et al: Permanent cardiac
stimulation after aortic valve replacement: Incidence, predictive
factors and long-term prognosis. Arch Mal Coeur Vaiss 87:
925–930, 1994.
Cases in Adult Congenital Heart Disease  161