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Viscero Atrial Situs (Solitus, Inversus, Ambiguous)

Chapter · January 2009

DOI: 10.1007/978-3-540-29676-8_7173

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Viscero Atrial Situs Abnormalities
G UIDO O PPIDO, C ARLO PACE N APOLEONE ,
G AETANO G ARGIULO
Pediatric Cardiac Surgery Unit, S. Orsola-Malpighi
Hospital, Bologna, Italy
Synonyms
Viscero atrial situs: solitus, inversus, ambiguous; Hetero-
taxia or heterotaxy syndrome; Asplenia and polysplenia
syndrome; Right and left isomerism; Bilateral or
double right and left sidedness; Right and left lat-
erality; Laterality abnormalities; Right-left axis malfor-
mations; Visceral symmetry; Ivemark syndrome
Definition and Characteristics
Human body is characterized by a typical left–right
asymmetry or laterality, which is normally defined situs
solitus. Variation in the development of the normal left–
right asymmetry, of the thoracoabdominal organs, may
either result in complete mirror image arrangement, situs
inversus, or in apparently chaotic arrangement, termed
situs ambiguous or heterotaxy (from the Greek words
heteros = other and taxis = order).
We may refer to situs visceroatrialis because in nearly
all cases situs atrialis and situs visceralis are concordant.
Situs inversus totalis is the mirror image arrangement
of all thoracoabdominal organs. It may or may not be
part of the “immotile cilia syndrome” or Kartagener’s
syndrome, clinically presenting with chronic sinusitis,
bronchiectasis, and male infertility.
Heterotaxy or situs ambiguous, typically involves the
following: rotation of the entire gastrointestinal tract,
lobation of the lungs, lobation and position of the liver,
atrial appendage’s morphology, and development of
the spleen. Heterotaxy may tend, more or less, to
“isomerism.” In other words, the complete failure to
break bilateral asymmetry can result in two apparently
right body sides (right atrial isomerism, asplenia
syndrome), or in two apparently left body sides (left
atrial isomerism, polysplenia or Ivemark syndrome).
Characteristics of asplenia and polysplenia are not
constant and are summarized in Table 1 [1,2].
QC by:
Prevalence
1. Situs viscero atrialis solitus = normal
2. Situs viscero atrialis inversus = 1:10,000/20,000
births. 20–25% of them have Kartagener’s syndrome.
3. Situs viscero atrialis ambiguous = 1:4,000/10,000
births. 1–3% of all the congenital heart diseases.
Genes
Familial situs abnormalities occur with autosomal
dominant, recessive, X-linked, and multigenetic inher-
itance. All possible situs variants such as solitus,
inversus, ambiguous can occur among different mem-
bers of the same heterotaxy family [3].
1. iv/iv mice (mapped on human chromosome 12) has
been identified in some forms of autosomal recessive
familial heterotaxy.
2. Mutations in connexin 43 have been recognized in
some other autosomal recessive familial cases of
heterotaxy. Connexin 43 (to chromosome 6) codes
a protein involved in gap junctions, which may play
a main role in the embryo organ development by
mediating the exchange of morphogenetic cell to cell
signals.
3. Mutations of nodal gene, mapped in the humans
to 10q21-q23, account for some cases of human
heterotaxy
4. Mutation in the ZIC3 gene (to Xq26.2), encoding
a putative zinc-finger transcription factor is described
as X-linked inheritance mechanism of heterotaxy.
Molecular and Systemic Pathophysiology
How the mutations translate into situs inverdsis is
incompletely understood. Situs inversus totalis may or
may not be part of the “immotile cilia syndrome” that is
characterized by the absence or abnormalities of the
dynein arms, connecting the nine pairs of microtubules
of cilia and clinically presenting with chronic sinusitis,
bronchiectasis, and male infertility.
Gap junctions may play a main role in the embryo
organ development by mediating the exchange of
morphogenetic cell-to-cell signals.
Diagnostic Principles Au1
Viscero atrial situs abnormalities may be suggested by
the position of the cardiac apex, bronchi length and
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2 Viscero Atrial Situs Abnormalities

Au4 Viscero Atrial Situs Abnormalities. Table 1 Characteristics of asplenia and polysplenia
Solitus Inversus Ambiguous Ambiguous
(asplenia) (polysplenia)
Male/female 1 >1 <1
Thoraco-abdominal organs
Spleen Left sided Right sided Absent Multiple small
spleens
Liver Right sided Left sided Median and Median and
symmetric – 76% symmetric – 67%
Stomach Left sided Right sided Right sided – 43% Right sided 50%
Left sided – 57% Left sided – 50%
Intestine Malrotation – 37% Malrotation – 27%
Malfixation Malfixation
Lungs Left: bilobed Right: bilobed Both trilobed – 85% Both bilobed – 58%
Right: trilobed Left: trilobed
Bronchi Left: long hy- Left: short Both short epiarterial Both long hypoar-
poarterial epiarterial terial
Right: short Right: long
epiarterial hypoarterial
Atrial appendages Left: finger-like Left: broad Both broad Both finger-like
triangular triangular
Right: broad Right: finger-
triangular like
Anal stenosis/atresia 6% Rare
Absence of gallbladder and biliary atresia Rare Frequent
Cardiac anomalies 0.8% 3–5% Nearly 100% More than 90%
Seno atrial node Often double Often absent
Atrio ventricular canal 85% 40 %
Total anomalous pulmonary venous return 70% (extra cardiac) 40% (intra-atrial)
Pulmonary stenosis/atresia 90% 30%
Transposition of the great arteries/double 80% 20%
outlet right ventricle
Azygos continuation of the interrupted Rare 85%
inferior vena cava
Bilateral superior vena cava 50% 40%
Dextrocardia 40% 40%
Functional single ventricle 50% 20%
Left heart obstruction Rare 40%

direction, stomach bubble, and liver shadow on the plain
thoracic and abdominal radiographs. Ultrasound, CT and
MR imaging, contrast gastrointestinal studies, echocar-
diography and angiocardiography may be required to
evaluate fully all the features of these anomalies. Howell-
Jolly bodies on peripheral blood smear found at birth may
Au2 suggest asplenia syndrome (Fig. 1). Presence or absence
of spleen tissue is anyhow best defined in children with
heterotaxy with hepatoiminodiacetic acid (HIDA) scan in
conjunction with radiocolloid scan.
Therapeutic Principles
The heart is the organ that most frequently leads to
clinically detectable abnormalities.
Mortality in the first year of life: 79% asplenia, 61%
polysplenia.
Therapy is basically surgical and is mainly focused
on the treatment of congenital heart disease.
Abdominal complication such as midgut volvulus,
due to gut malrotation and malfixation, may require
urgent surgical treatment.
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Viscero Atrial Situs Abnormalities 3

Au4 Viscero Atrial Situs Abnormalities. Figure 1 {A,D,D} Common inlet left ventricle with pulmonary atresia and total
anomalous pulmonary venous return in asplenia syndrome or right isomerism. This intraoperative view clearly
shows both atrial appendages to be morphologically right, with the characteristically broad base of implant and the
typical pyramidal shape. Pulmonary atresia is a recurrent feature in asplenia syndrome and is clearly
recognizable in this patient as well.

References 2. Uemura H, et al. (1995) Analysis of visceral heterotaxy

according to splenic status, appendage morphology, or
1. Ticho BS, et al. (2000) Extracardiac anomalies in the both. Am J Cardiol 76(11):846–849
heterotaxy syndromes with focus on anomalies of midline- 3. Kosaki K, Casey B (1998) Genetics of human left-right
associated structures. Am J Cardiol 85(6):729–734 axis malformations. Semin Cell Dev Biol 9(1):89–99
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