Pentalogy of Fallot

Pentalogy of Fallot means tetralogy of Fallot (TOF) with a secundum type of ASD. Pentalogy means that five anomalies are present ( pente , five, Greek), the four anomalies of the tetralogy of Fallot (pulmonary outflow tract obstruction [stenosis or atresia], subaortic VSD, overriding aorta, and right ventricular hypertrophy) plus an ASD II. Although found in the older literature, this diagnosis is not routinely used today.

How common is an ostium secundum type of ASD found in association with TOF? In an effort to answer this question, we did a study of 100 randomly selected postmortem cases from the 1980s and 1990s. An ostium secundum type of ASD was found in 35 of these 100 cases (35%). The ASD was so large as to be regarded as resulting in common atrium in 5 of these 35 patients. Thus, a very large defect (common atrium) occurred in 14% of ASD II and in 5% of the series of tetralogy patients as a whole.

To summarize, pentalogy of Fallot occurred in approximately one-third of our autopsied cases of TOF (35%).

Common Atrium

Common atrium means, as the name indicates, that a very large ASD is present—so large that the atria are in common, that is, essentially undivided. Thus, the atrial septum is largely or totally absent.

There are two main anatomic types of common atrium:

• 1.
  

  with a divided AV canal (see Figs. 9.4 to 9.6 ), that is, with a separate mitral and tricuspid valve, the anterior leaflet of the mitral valve often being cleft, as in the Ellis-van Creveld syndrome (chrondoectodermal dysplasia, i.e., achondroplasia with defective development of skin, hair, and teeth; polydactyly; and defect cardiac septation in about 50%, autosomal recessive inheritance); and

  
  
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  with a common AV canal, that is, with a common AV valve and an AV septal defect (see Chapter 11 ). Dr. Jesse Edwards calls this type of common atrium “the forgotten type of common AV canal,” in which there is an AV septal defect that typically is confluent with a large secundum type of ASD due to marked deficiency or absence of the components of the atrial septum. Thus, there are confluent secundum atrial and AV septal defects, resulting in a huge deficiency of cardiac septation.

Are there any other syndromes in which interatrial communications are characteristic? Yes. The heterotaxy syndrome with congenital asplenia, polysplenia, and right-sided but otherwise normally formed spleen spring to mind. Analysis of 95 postmortem cases of asplenia and 68 postmortem cases of polysplenia revealed the following findings ( Table 9.3 ):

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  A PFO or an intact atrial septum was much more common in the polysplenia syndrome (22%) than in the asplenia syndrome (2%) ( p < .001) (see Table 9.3 ).

  
  
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  An ASD II was somewhat more frequent with polysplenia (31%) than with asplenia (20%), but this difference was not statistically significant (see Table 9.3 ).

  
  
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  An ASD I (incompletely common AV canal) was commoner with asplenia (23%) than with polysplenia (10%) ( p < .05) (see Table 9.3 ).

  
  
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  Common atrium was much more frequent with asplenia (72%) than with polysplenia (32%) ( p < .001) (see Table 9.3 ).

  
  
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  Overall, visceral heterotaxy with asplenia had an interatrial communication more often (97.89%) than did visceral heterotaxy with polysplenia (77.94%) ( p < .001) (see Table 9.3 ).

What about visceral heterotaxy with a normally formed but right-sided spleen? As discussed in Chapter 29 , we know too little about this least frequent heterotaxy syndrome to make any statistically supported conclusions (n = 5). The data are as follows: PFO, 1 case (20%); ASD II, 1 case (20%); and common atrium, 3 cases (60%).

Aneurysm of Septum Primum

When tricuspid atresia is associated with a PFO or a restrictive ostium secundum type of ASD, the septum primum can form a prominent aneurysm that bulges into the LA ( Fig. 9.12 ). The aneurysm of the septum primum can form a supramitral stenosing membrane, or the aneurysm can prolapse downward into the mitral canal and into the left ventricular inlet (see Fig. 9.12 ), resulting in a rare form of congenital supramitral or intramitral stenosis. The septum primum appears to bulge progressively more markedly into the LA, below the ostium secundum, that is, below the superior concave rim of septum primum that delimits the so-called ostium secundum inferiorly. In advanced cases (see Fig. 9.12 ), the septum primum resembles a suspended bird’s nest—like the nest of an oriole—that is, dangling from the anterior and posterior attachments of the septum primum to the left side of the superior limbic band of the septum. These attachments are called the anterior and posterior horns of the septum primum (see Fig. 9.12 ). The concavity of the septum primum aneurysm faces the RA and receives the thrust of right atrial systole into the concavity of the obstructive septum primum. The right atrial blood then appears to swirl upward, over the superior narrowed rim of the septum primum into the LA and then downward around the bulging convexity of the septum primum, through the obstructed mitral canal, and into the left ventricle (LV).

This patient with transposition {S,D,D} and tricuspid atresia had a huge aneurysm of septum primum (Sept I) that bulged into the left atrium (LA) and then herniated downward and through the mitral valve into the left ventricular inflow tract, resulting in severe supramitral and intramitral stenosis. Why did this enormous aneurysm of septum primum occur? Our hypothesis is that septum primum was obstructive. Notice how relatively small and superior the ostium secundum is, that is, the space above the concave and superiorly oriented upper margin of the septum primum, between the anterior cornu (horn) and the posterior cornu, by which septum primum is attached to the left atrial aspect of the superior limbic band of septum secundum. Before this LA was opened, the small ostium secundum “opened” into the left atrial free wall, increasing the obstruction of the interatrial communication. Given the coexistence of tricuspid atresia, the prenatal right-to-left interatrial shunt was greater than normal. Note also that there were no fenestrations within this restrictive septum primum—which, had they been present, would have made septum primum less obstructive. This type of aneurysm of septum primum is often referred to in the literature as an atrial septal aneurysm (which it is). PFO, Patent foramen ovale.

When there is congenital mitral atresia or severe stenosis, the septum primum can bulge in the opposite direction, into the RA. I cannot recall having seen an aneurysm of the septum primum that produced supratricuspid or intratricuspid obstruction. For reasons unknown, very impressive aneurysms of the septum primum have been associated with tricuspid atresia, as in Fig. 9.12 , rather than with mitral atresia or the hypoplastic left heart syndrome (HLHS). Time may be the critical variable. Systemic venous obstruction may be better tolerated than pulmonary venous obstruction, allowing more time for the development of a leftward bulging aneurysm with tricuspid atresia than for a rightward bulging aneurysm with mitral atresia (speculation).

However, the ostium secundum type of ASD typically is associated with underdevelopment of the septum primum, with or without fenestrations of or within the septum primum. The septum primum typically is regurgitant, not obstructive. Prenatally, the flap valve function of the septum primum may permit significant regurgitation of blood from the left heart into the right heart, resulting in underdevelopment of the left heart, that is, HLHS without mitral or aortic obstruction, with overdevelopment of the right heart. We have seen patients treated surgically for the hypoplastic left heart syndrome, when the basic diagnosis was really ASD II with significant LA-to-RA regurgitation in utero and postnatally.

This is an important clinical lesson: An ASD II can manifest as HLHS. And the left heart is relatively hypoplastic compared with the right heart. How does one diagnostically recognize this type of HLHS? There is no stenosis or atresia at any left heart level, only hypoplasia (without dysplasia). In this type of HLHS, the basic diagnosis is ASD II with significant left-to-right regurgitation (shunting).

It is the blood of the via sinistra coming from the placenta up the IVC, past the right venous valve (Eustachian and Thebesian valves) to the right, past the left venous valve and septum primum to the left, and then about 60% of the IVC’s blood stream goes over the concave top of the septum primum into the LA ( Fig. 9.13 ).

View Through the Opened Right Atrium of a Newborn’s Septum Primum (Septum I) Which Is Furthest to the Left.

Slightly to the right, at the base of septum primum, is the left leaflet of the sinoatrial valve (SA V), often called the left venous valve. Further to the right is the lumen of the inferior vena cava (IVC). To the right of the IVC is the Eustachian valve (Eust. V), which is the right leaflet of the SA V, often called the right venous valve. Thus, the left leaflet of the SA V is really bifid, consisting of two parts: septum primum and the left venous valve, which is normally vestigial. Septum primum is the largest venous valve in the body and is the main component of the bifid left venous valve mechanism. The largest venous valve in the body, the SA V, is not normally incompetent (regurgitant), as is commonly thought. Instead, because of the septum primum, the SA V is normally competent in the sense that it prevents regurgitation from left atrium to right atrium. But the SA V normally is incompetence between the right atrium and the venae cavae. Abnormally, the right venous valve can be very well developed, dividing the medial caval compartment from the more lateral appendage and tricuspid valve compartment, resulting in cor triatriatum dextrum. This is why the right venous valve is normally incompetent—so that it will not be obstructive.

This is the via sinistra— the left road (Latin)—of the oxygenated placental venous return that normally goes from the IVC into the left heart, and normally stays in the left heart, if the septum primum (the flap valve of the foramen ovale) is normal in form and function (essentially nonregurgitant). If the blood of the via sinistra then regurgitates out of the left heart, the result can be HLHS without mitral or aortic or other dysplasia (“pure” hypoplasia).

Hence, an important question for consideration is: Why can the septum primum be underdeveloped, and/or fenestrated, or absent? What is known about the development of the septum primum?

Embryology of Septum Primum

Where do all those fenestrations, holes, and deficiency in the growth of the septum primum come from that result in the great majority of ostium secundum ASDs (see Figs. 9.2 , 9.4 to 9.9 , and 9.11 )? Is there anything known about the development of the septum primum that may make fenestrations and deficiency of the septum primum more readily understandable?

Yes indeed, there is. We were very well impressed by the Ph.D. thesis of Mary Jessica Charles Hendrix in 1977 that appears highly relevant to this question. In an electron and light microscopic study of the development of the atrial septum in the chick and in the human embryo, Hendrix found the following:

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  In the chick embryo (“full term” or hatching in 21 days), at 3 days of age a common atrium is present. The beginnings of the septum primum (called the atrial septum) are present dorsally and cephalically, but without fenestrations in the septum primum ( Fig. 9.14 ).

  
  

  
  

  
  

  

  
  

  
  

  Right Lateral View of a 3-Day-Old Embryonic Chick Heart (Hamilton-Hamburger Stage 18).

  
  

  The right lateral atrial wall has been removed, revealing a common (undivided) atrium (A). The septum primum, the atrial septum (AS), is seen cephalically and dorsally. Note that this early septum primum displays no fenestrations. The ventricle (V) and the truncus arteriosus (TA) are also seen. For correct spatial orientation, rotate this figure approximately 45 counterclockwise. The common atrium lies behind the ventricle, not above it.

  
  

  Scanning electron micrograph ×190 by Mary Jessica Charles Hendrix in 1977, reproduced with permission from her PhD thesis, entitled An Investigation of Atrial Septation in the Chick and Human Heart: An Electron and Light Microscopic Study. Graduate School of Arts and Sciences, The George Washington University, Washington, DC.

  
  
  
  
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  By the 4th day of incubation, fenestrations start to appear in the septum primum of the chick embryo ( Fig. 9.15 ).

  
  

  
  

  
  

  

  
  

  
  

  Atrial Septum (AS), That Is, Septum Primum, of a 4-Day-Old Chick Embryo (Stage 23), Left Atrial View.

  
  

  Fenestrations that Hendrix called foramina secundua (FS), have appeared within the mid-dorsal portion of septum primum and averaged 9 microns (μ) in diameter. The interatrial communication at the anteroinferior free margin of septum primum (FP), also known as ostium primum. For correct spatial orientation, rotate this figure 90 degrees clockwise. In the embryo, the ostium primum (FP) is in front of septum primum (AS), not below it.

  
  

  Scanning electron micrograph ×625 by Mary Jessica Charles Hendrix in 1977, reproduced with permission from her PhD thesis, entitled An Investigation of Atrial Septation in the Chick and Human Heart: An Electron and Light Microscopic Study. Graduate School of Arts and Sciences, The George Washington University, Washington, DC.

  
  
  
  
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  By the 5th day of gestation (incubation), multiple fenestrations have appeared in the septum primum of the chick embryo ( Fig. 9.16 ). If this were the heart of a postnatal human, we would certainly make the diagnosis of an ASD II due to multiple large fenestrations in septum primum.

  
  

  
  

  
  

  

  
  

  
  

  Septum Primum of a 5-Day-Old Embryonic Chick Heart (Stage 28), Left Atrial View.

  
  

  (A) Fenestrations of septum primum (FS) are now much larger, but remain restricted to the mid-dorsal and dorsal portions of septum primum. Many minute fenestrations are also observed throughout the atrial septum. Musculi pectinati (MP) and the entrance of the pulmonary vein (PV) are also seen (×160). (B) Fenestrations of septum primum (FS) are even more striking in this 5½-day-old chick embryo. Fine strands of endocardium-covered septum primum separate these prominent fenestrations (×290). This figure has been rotated 90 degrees counterclockwise so that the pulmonary vein (PV) lies behind the fenestrated septum primum.

  
  

  Scanning electron micrograph by Mary Jessica Charles Hendrix in 1977, reproduced with permission from her PhD thesis, entitled An Investigation of Atrial Septation in the Chick and Human Heart: An Electron and Light Microscopic Study. Graduate School of Arts and Sciences, The George Washington University, Washington, DC.

  
  
  
  
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  By 7 days of incubation, multiple large fenestrations are still present in the septum primum ( Fig. 9.17 ). The right venous valve is also fenestrated, forming a rete Chiari (to the right of the septum primum, unlabeled, see Fig. 9.17 ).

  
  

  
  

  
  

  

  
  

  
  

  The Atrial Septum of a 7-Day-Old Chick Embryo Heart (Stage 31), Right Posterolateral View (×125).

  
  

  The fenestrations in septum primum (FS) remain prominent in this right atrial (RA) view. The very fenestrated structure to the right of the fenestrated septum primum is either the left or the right venous valve (I am not sure which). Fenestration of the right or left venous valve (usually of the right venous valve) is the developmental basis of the rete Chiari or Chiari’s network, when these fibrous strands persist into postnatal life and remain within the right atrium. In their development, venous valves fenestrate. Septum primum is the major leftward component of the left venous valve. The structure known as the left venous valve is the minor rightward component of the left venous valve mechanism which is bifid, having leftward (septum primum) and rightward (left venous valve) components. Here we see fenestration of both components, septum primum to the left (labeled FS) and venous valve to the right (unlabeled). For correct spatial orientation, rotate this figure about 45 degrees counterclockwise. LV, Left ventricle; RV, right ventricle.

  
  

  Scanning electron micrograph by Mary Jessica Charles Hendrix in 1977, reproduced with permission from her PhD thesis, entitled An Investigation of Atrial Septation in the Chick and Human Heart: An Electron and Light Microscopic Study. Graduate School of Arts and Sciences, The George Washington University, Washington, DC.

  
  
  
  
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  By 9 days of incubation, the septum primum is still so fenestrated in its mid-dorsal and dorsal portions that it resembles a coarse mesh of cords that are covered with endothelium ( Fig. 9.18 ). At this stage, the chick is 43% through its gestation.

  
  

  
  

  
  

  

  
  

  
  

  Left Atrial View of Septum Primum During the Ninth Day of Cardiac Morphogenesis (×390).

  
  

  Note that the endocardium-covered cords (C) surrounding the fenestrations (FS) in septum primum are becoming coarser or thicker in appearance.

  
  

  Scanning electron micrograph by Mary Jessica Charles Hendrix in 1977, reproduced with permission from her PhD thesis, entitled An Investigation of Atrial Septation in the Chick and Human Heart: An Electron and Light Microscopic Study. Graduate School of Arts and Sciences, The George Washington University, Washington, DC.

  
  
  
  
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  By 11 days of age, 52% of the way through gestation, the cords separating the fenestrations (foramina secunda of Hendrix) are becoming noticeably thicker, and the fenestrations are getting somewhat smaller ( Fig. 9.19 ).

  
  

  
  

  
  

  

  
  

  
  

  Left Atrial View of an 11-Day-Old (Stage 37) Chick Embryo’s Septum Primum (×410).

  
  

  The endothelium-covered cords (C) of septum primum are becoming thicker, averaging 38 μ in width. The fenestrations in septum primum (FS) average 175 μ in length and 100 μ in width. The arrow points at what appears to be nearly a perforation.

  
  

  Scanning electron micrograph by Mary Jessica Charles Hendrix in 1977, reproduced with permission from her PhD thesis, entitled An Investigation of Atrial Septation in the Chick and Human Heart: An Electron and Light Microscopic Study. Graduate School of Arts and Sciences, The George Washington University, Washington, DC.

  
  
  
  
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  The septum primum at 14½ days in the chick embryo is seen in Fig. 9.20 . By 18½ days of gestation (88% of the way to “full term”) the cords have become much thicker and the fenestrations are fewer and smaller ( Fig. 9.21 ).

  
  

  
  

  
  

  

  
  

  
  

  Left Atrial View of a Portion Of Septum Primum of a 14½-Day-Old Chick in Ovo (Stage 40+).

  
  

  The endothelium-covered cords (arrows) surrounding the fenestrations in septum primum normally continue to thicken. (A, ×420, B, ×720.)

  
  

  Electron micrograph by Mary Jessica Charles Hendrix in 1977, reproduced with permission from her PhD thesis, entitled An Investigation of Atrial Septation in the Chick and Human Heart: An Electron and Light Microscopic Study. Graduate School of Arts and Sciences, The George Washington University, Washington, DC

  
  

  
  

  
  

  

  
  

  
  

  By 18½ days of age in ovo (stage 44+), as this left atrial view of septum primum shows, the now very thick endothelium-covered cords surrounding the perforations (FS) are greatly reducing the size of these fenestrations (×290). This figure has been rotated through 180 degrees so that the superior free margin of septum primum will face cephalad. This is why the labels FS and P are upside-down.

  
  

  Scanning electron micrograph by Mary Jessica Charles Hendrix in 1977, reproduced with permission from her PhD thesis, entitled An Investigation of Atrial Septation in the Chick and Human Heart: An Electron and Light Microscopic Study. Graduate School of Arts and Sciences, The George Washington University, Washington, DC.

  
  
  
  
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  By the time of hatching at 21 days gestation, the septum primum is normally essentially intact, with few or no remaining fenestrations ( Fig. 9.22 ).

  
  

  
  

  
  

  

  
  

  
  

  The Chick Atrial Septum at Hatching, 21 Days Gestational Age (Stage 46), Left Atrial View of Septum Primum (×1200).

  
  

  (A) The depressions (X) in the septum were interpreted as being due to the unevenness of the fusing endocardium–covered cords that occluded the fenestrations or perforations in septum primum that are normal earlier morphologic features (see Figs. 9.15 to 9.21 , inclusive). (B) By 2 days after hatching, the atrial septum (AS), that is, septum primum, normally has a relatively smooth surface contour, as seen from the left atrium (×360). Thus, the appearance of multiple fenestrations in septum primum, that is part of the standard textbook account of atrial septation, turns out to be very important, not as the origin of ostium secundum, as the textbooks say. (Ostium secundum is merely the space above the concave superior free margin of septum primum). Abnormally, if they persist postnatally, these fenestrations or perforations of septum primum are by far the commonest anatomic type of secundum ASD. The standard textbook account of the embryology of atrial septation does not say anything about the gradual disappearance of these fenestrations in septum primum, so well documented by Hendrix.

  
  

  Scanning electron micrograph by Mary Jessica Charles Hendrix in 1977, reproduced with permission from her PhD thesis, entitled An Investigation of Atrial Septation in the Chick and Human Heart: An Electron and Light Microscopic Study. Graduate School of Arts and Sciences, The George Washington University, Washington, DC.

  
  

The Pathologic Anatomic Findings in 640 Human Cases of Secundum Atrial Septal Defect

In an effort to amplify our understanding of ASD II, a large study was undertaken of the records of 640 autopsied human patients from the Cardiac Registry of Children’s Hospital Boston. All of these cardiac pathology examinations, description, and diagnoses were done by the author or by Stella Van Praagh, M.D., ably assisted over the years (1966 to 1996) by numerous excellent fellows. The heart specimens date from 1950 to 1996, inclusive. This study has not been published or presented previously.

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  Sex: Of these 640 patients, the sex was known in 631 (98.59%). In consultations, the patient’s sex was sometimes not stated (in 9 of 640 cases, 1.4%). In these 631 patients with ASD II, there were 335 males (53%) and 296 females (47%), and the male-to-female ratio was 1.13:1.0. Thus, in this series of secundum ASD patients as a whole, there was a mild male preponderance.

  
  
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  Age at Death: In this series of 640 patients with ASD II, 1 case was excluded because happily this patient did not die. Case number 637 (S94-2327) was a 10-year-old girl who had a Clamshell Septal Occluder Device that was explanted because of disarticulation and fracture of one right atrial arm of the device and a large right atrial thrombus associated with the right atrial umbrella. A 4-mm piece of metal was found to be sticking out of the right atrial umbrella. Also the left atrial umbrella had one unextended arm opposite the broken right atrial arm. The Clamshell device and the right atrial thrombus were removed uneventfully surgically and the secundum ASD was closed with a pericardial patch.

Of the 639 patients with secundum ASD who died, the age at death was known in 619 (97%). The mean age at death was 3.17 years. The standard deviation was ± 8.04 years. The age at death ranged from 65 years to 0 (stillbirths or fetal demises). The median age at death was 4 weeks and 5½ days, that is, 4.78 weeks, which may be rounded off to 5 weeks of age.

The median age at death (5 weeks of age) reflects much more accurately than does the mean age at death (3 years and 2.4 months of age) what really happened to these 619 patients with ASD II. The very young median age at death accurately indicates that these patients almost always had additional, more severe forms of congenital heart disease, as will be seen.

When Secundum Atrial Septal Defect II Was the Most Important Clinical Problem

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  Sex: Male, 3 of 13 (23%); female, 10 (77%). The sex ratio was male-to-female = 3:10 (.3), or female-to-male = 10:3 (3.3/1.0). Hence, when ASD II was the main clinical problem, the expected female preponderance was found.

  
  
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  Age at Death: Of the 12 deceased patients (the Clamshell case, patient 637, did not die), the mean age at death was 25.39 years. The standard deviation was ± 18.14 years. The range was from 0.625 years (7½ months) to 65 years. The median age at death was 24.75 years.

These statistics concerning the age at death are very much older than those found for the series as a whole (see earlier), indicating that when a secundum ASD is the patient’s main clinical problem, fatalities almost always occur in the young adult age group, not in the pediatric age range. This observation appears to explain why there are so few patients in our postmortem series in whom ASD II was the patient’s primary clinical problem. Thus, secundum ASD is a “sleeper.” It must be diagnosed accurately and treated effectively early in life, in order to avoid death in young adulthood.

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  Salient Features: All 13 of these patients had isolated ASD II; that is, no other form of clinically significant congenital heart disease was present.

The ASD was large in 12 of 13 patients (92%) ( Fig. 9.23 ). In one case, this assessment could not be made because the ASD had been surgically closed with direct sutures. Typically, the ASD was described as large, very large, or huge, with marked deficiency of the septum primum, resulting in a common atrium or almost a common atrium.

Absence of Septum Primum Resulting in a Huge Ostium Secundum Type of Atrial Septal Defect.

(A) Opened right atrium, tricuspid valve, and right ventricle of the heart of a 7½-month-old white boy with a very large secundum type of atrial septal defect (20 × 10 mm). Septum primum was absent. The patient had rapid respirations since birth (140/min). Dying in 1952 without cardiac surgery, he had severe pulmonary congestion and marked bilateral chronic pneumonitis. Thus, a large secundum atrial septal defect can cause death in infancy. (Photograph taken at the time of autopsy). (B) Opened left atrium, mitral valve, and left ventricle of a 13-year-old white girl who died in 1964 because of a huge, unoperated secundum atrial septal defect. Because of absence of septum primum, she had a common atrium with intractable congestive heart failure and ascites (500 cc). (Photograph taken at autopsy.)

Death occurred postoperatively in 7 of these 13 patients (54%), early in our experience. We have not seen at autopsy a patient from our institution in whom ASD II was the primary clinical problem for the past 22 years, not since 1983.

However, we had one consultation in 1992 concerning a patient from another hospital (Case 579, C92-165). This patient was a 15 3/12-year-old young woman who had a very large ASD II. At 2 3/12 years, she underwent pericardial patch closure of her atrial defect. Postoperatively, she had sick sinus syndrome. At 10 9/12 years of age she received a pacemaker. Subsequently, she developed atrial fibrillation that spontaneously converted to normal sinus rhythm. Sudden unexpected death occurred 13 years postoperatively, in what appeared to be an arrhythmic demise. This case emphasizes the great importance of avoiding injury to the sinoatrial (SA) node and the SA nodal artery during atriotomy and atrial repair. Knowing exactly where these structures are located and taking care to avoid them (see Chapter 2 ) should make it possible to avoid sick sinus syndrome and its sequelae.

Pulmonary vascular obstructive disease (PVO) was very prominent in 4 of these patients. Right-to-left atrial shunting, polycythemia, cyanosis, clubbing, systemic embolization, stroke, and brain abscess all occurred.

Right-to-left shunting at any cardiac level (atrial, ventricular, or great arterial) is the Eisenmenger reaction of Dr. Paul Wood, who developed the Wood units in which pulmonary resistance is measured. The Eisenmenger reaction (right-to-left shunting because of elevated pulmonary vascular resistance) is not to be confused with the Eisenmenger complex (large subaortic VSD, aortic overriding, and right ventricular hypertrophy, but without pulmonary outflow tract obstruction and hence distinct from TOF). Thus, late-stage ASD II typically displays the Eisenmenger reaction (but not the Eisenmenger complex).

When Atrial Septal Defect II Was an Important Part of the Patient’s Main Clinical Problem

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  In 8 patients, the secundum ASD was an important part of the patient’s main clinical problem (8/640 = 1.25%), but not the whole clinical problem.

  
  
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  Sex: Male, 1; females, 7; male-to-female ratio 1:7 (.14) or female-to-male ratio, 7:1 (7).

  
  
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  Age at Death: Mean, 15.99 years; standard deviation, ± 17.07 years; range, 5 weeks to 53 years; and median, 13 years.

  
  
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  Salient Features: All had large secundum ASD. Rheumatic heart disease had occurred in 2 of these 8 patients. One had chronic mitral regurgitation that distended the LA and enlarged the ASD II. The other had severe rheumatic mitral stenosis that had been treated (in the 1950s and 1960s) with old and recent mitral valvuloplasties. This 53-year-old woman had a large ASD II (20 mm in diameter) with a very deficient septum primum. This combination of findings—secundum ASD and mitral stenosis—is known as the Lutembacher syndrome ( pronounced lootem-baker, i.e., in the German way), despite the fact that Rene Lutembacher (1884–1968) was a French physician from Paris who described this association in 1916, which was a very busy time in Paris.

  
  
  
  
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    A second patient had mitral regurgitation , but its cause (congenital or acquired) was not definitely established.

    
    
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    Down syndrome was present in 2 of these 8 patients with large secundum ASDs.

    
    
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    Multiple congenital anomalies (intellectual disability, hypospadias, hypoplastic penis, and cryptorchidism), sepsis (perirectal pelvic abscess related to Escherichia coli and Aerobacter, esophagitis, gastroenteritis, duodenal ulcers from which Monilia were cultured, tracheobronchitis, pulmonary edema, and bronchopneumonia), and pulmonary hemorrhage occurred in 1 patient each. Congestive heart failure and PVO were prominent in 3 patients each.

  
  

So, let us assume that most experienced observers know that ASD II can be the patient’s primary clinical problem or that ASD II can be associated with other disease processes that together may constitute the patient’s main clinical problem (as earlier).

But now we must consider a great unknown: What about the more than 95% of pediatric patients that have a secundum ASD, but in whom the ASD II is clinically overshadowed by other “more serious” forms of congenital heart disease? What do these patients have? What is ASD II associated with and masked by? This is what most books and papers on secundum ASD do not mention. We shall now attempt to answer these questions.

When Secundum Atrial Septal Defect II Is Present, but Not the Patient’s Primary Clinical Problem

A secundum type of ASD was present in 627 of 640 patients in this study, but the ASD II was not the patient’s main clinical problem (97.97%). What was? An attempt is made to answer this question in Table 9.4 .

Multiple congenital anomalies were the most common main clinical problem, being present in 183 patients (29.19% of this series, see Table 9.4 ). “Multiple congenital anomalies” means that malformations were present in two or more systems, not in the cardiovascular system only. Other well-recognized syndromes are presented as such and are not classified as multiple congenital anomalies (see Table 9.4 ); for example: Down syndrome, 48 patients (7.66%); DiGeorge syndrome, 8 patients (1.28%); scimitar syndrome, 8 patients (1.28%); Noonan syndrome, 5 patients (0.8%); trisomy 18, 4 patients (0.64%); Marfan syndrome, 3 patients (0.48%); Potter syndrome, 2 patients (0.32%); Turner syndrome, 2 patients (0.32%); VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) association; CHARGE ( coloboma , heart defects, atresia choanae [also known as choanal atresia], growth retardation, genital abnormalities, and ear abnormalities) association, 1 patient (0.16%), and so on.

Representative examples of “multiple congenital anomalies” are as follows: TOF with secundum ASD (pentalogy of Fallot), anomalous right subclavian artery, omphalocele, and malrotation of the intestines (Case 7); large secundum ASD (20 × 15 mm), totally anomalous pulmonary venous connection to the portal vein with patent ductus venosus, and craniosynostosis of the sagittal suture posterior to the anterior fontanelle (Case 25); secundum ASD, septum primum covering only half of the interatrial communication, pulmonary valvar stenosis with intact interventricular septum, pectus excavatum, malformation of the brain with glial nodules of the temporal lobes, diffuse ependymal gliosis, decreased cells of the dentate nucleus, and intellectual disability. This 12-year-old boy fell and sustained a skull fracture with subdural hematoma and cerebral hemorrhage (Case 26).

Thus, what is meant by multiple congenital anomalies is multisystem pathologic processes (not the cardiovascular systemic only), that does not constitute a well-recognized syndrome at the present time.

Table 9.4 contains a great deal of information and is essentially self-explanatory. But what this table does not do is present the many varying combinations of anomalies—cardiovascular and noncardiovascular—that occurred together.

Segmental anatomy {IS,D,S} polysplenia means the segmental set of visceral situs inversus with atrial situs solitus, D-loop ventricles, and solitus normally related great arteries, with visceral heterotaxy and polysplenia, that is, visceroatrial situs discordance; {AI,L,I} polysplenia indicates the segmental set of visceral situs ambiguus with situs inversus of the atria, L-loop ventricles, and inverted normally related great arteries, with visceral heterotaxy and polysplenia; and {S,L,I} means the set of situs solitus of the viscera and atria, L-loop ventricles, and inverted normally related great arteries. In {S,L,I}, the segmental alignments are AV discordance with ventriculoarterial concordance. In words, {S,L,I} may also be called ventricular inversion with inverted normally related great arteries in visceroatrial situs solitus. {S,L,I} is a brief convenient abbreviation.

In the process of doing the study to identify the main clinical problems of these patients with ASD II, a number of rare and fascinating forms of congenital heart disease were found that merit recording here:

Ostium primum type of ASD, without a cleft in the anterior leaflet of the mitral valve (Case 113, A63-60) . This case answers the question of whether it possible to have an incomplete form of common AV canal with a partial form of AV septal defect (i.e., an ostium primum ASD), but without the typical cleft in the anterior leaflet of the mitral valve. As the case of this 3-day-old girl with Down syndrome proves, the answer is, yes, rarely. The reverse, that is, a canal type of cleft in the anterior mitral leaflet but without an ostium primum type of ASD, is more frequent, but still uncommon. Thus, partial forms of common AV canal are numerous and highly variable.

Totally anomalous pulmonary venous connection (TAPVC) with physiologically normal pulmonary venous drainage. This surprising situation was found in a 1-month-old boy (Case 173, A67-216) with an ASD II (fenestrated septum primum), dextrocardia, TGA {S,L,L}, pulmonary atresia (infundibular and valvar), incompletely common AV canal, hypoplastic LV (right-sided), common-inlet right ventricle (RV) (left-sided), TAPVC to the left innominate vein, to the left SVC (LSVC), to the LA (because of a large coronary sinus septal “unroofing” defect). The aortic arch was right-sided, and the right-sided patent ductus arteriosus (PDA) was closing, leading to death. As this rare case indicates, there is a valid distinction between totally anomalous pulmonary venous connection (TAPVC) and totally anomalous pulmonary venous drainage (TAPVD).

Umbilical vein running anteriorly and superiorly to the liver to connect with the IVC. Normally the umbilical vein runs inferiorly to the liver, into the porta hepatis, where it connects with the portal vein and then continues as the ductus venosus, running to the right of and then posteriorly to the caudate lobe of the liver where the ductus venosus connects with the IVC. This anterosuperior umbilical vein was found in a 15-day-old white boy (Case 294, A76-53) with a large secundum ASD, TGA {S,D,D}, a small subpulmonary conoventricular type of VSD, and a PDA. During cardiac catheterization, the subaortic infundibulum was perforated, leading to cardiac tamponade and death.

An anterosuperior left umbilical vein running in front of and above the liver to drain into the IVC was also found in a 12-day-old girl (Case 597). She had a secundum ASD, because of multiple fenestrations in the septum primum, and a paramembranous conoventricular type of VSD. She also had multiple congenital anomalies, that is, right hydronephrosis with right ureteropelvic stenosis. In addition, this 12-day-old girl from another institution had a widely patent ductus arteriosus. Autopsy revealed that the left pulmonary artery had been ligated inadvertently and that the ductus arteriosus remained widely patent.

An anterosuperior umbilical vein is anatomically anomalous, but physiologically normal in the sense that it drains appropriately into the IVC, but without any “liver factors” (which may be important for the prevention of arteriovenous malformations).

Tracheal atresia with bronchoesophageal fistulae. Tracheal atresia is an exceedingly rare anomaly in our experience. This malformation was found in a 2½-year-old boy (Case 298, A76-121) with a small ASD II (fenestrations in the septum primum), visceral heterotaxy with polysplenia and TOF {S,D,S}, that is, pentalogy of Fallot. This patient also had hypoplasia of the stomach (microgastria), malrotation of the intestines, Meckel’s diverticulum, prematurity, and severe pulmonary edema and hemorrhage. We think that tracheal atresia is very rare and uniformly lethal, at least at the present time.

Parachute mitral valve and Ebstein anomaly of the tricuspid valve—a rare combination. A 7-week-old boy (Case 302, C76-26) had a small ASD II (4 × 2 mm), with TOF, that is, pentalogy of Fallot, plus an incompletely common AV canal. The mitral valve had congenital mitral stenosis with fusion of the papillary muscles, that is, parachute mitral valve. The mitral orifice consisted of the cleft in the anterior leaflet of the mitral valve. The tricuspid valve displayed Ebstein anomaly with abnormal chordae tendineae, obliteration of the interchordal spaces, muscularization of the anterior leaflet of the tricuspid valve, and severe tricuspid regurgitation. Thus, in addition to pentalogy of Fallot, this patient also had congenital mitral stenosis and severe congenital tricuspid regurgitation. The combination of parachute mitral valve and Ebstein anomaly of the tricuspid valve is rare. This patient may be considered to have a double pentalogy: (1) pentalogy of Fallot and (1) TOF, (2) ASD II, (3) incompletely common AV canal, (4) parachute mitral valve, and (5) Ebstein anomaly of the tricuspid valve, with 1 to 5 comprising the second pentalogy.

Congenital Lutembacher syndrome. An 11-week-old white girl (Case 312, A77-191) had an ASD II (valve incompetent patent foramen ovale [PFO] with a large left-to-right shunt at the atrial level) and a double-orifice mitral valve. The anterior orifice was smaller than the posterior orifice, and there was a bridge of fibrous tissue connecting the anterior and posterior mitral leaflets. Cardiac catheterization revealed a 3-mm diastolic gradient between the LA and the LV, confirming the presence of congenital mitral stenosis. Thus, this patient had both features of Lutembacher syndrome: an ASD II, and congenital mitral stenosis.

This patient also had a multiple muscular VSD (five) and a preductal coarctation of the aorta (3 mm in internal diameter).

Although most cases of Lutembacher syndrome appear to be due to acquired mitral stenosis (often rheumatic) plus a secundum ASD or a stretched PFO, this case indicates that Lutembacher syndrome can result entirely from congenital heart disease.

Concordant alignments between discordant atria and ventricles. This is Dr. Henry Wagner’s amazing case (Case 313, C77-8, sex and age at death unknown to us) of double-outlet RV (DORV) {S,L,D} with AV alignment concordance ( Fig. 9.24 ). The ASD II was large. The patient had mesocardia with a leftward pointing apex and right-sided JAA. There were crisscross AV relations, the mitral valve being superior relative to the tricuspid valve. (It is very rare for the tricuspid valve to be inferior to the mitral valve. Almost always, it is vice versa: tricuspid valve superior to the mitral valve.) Other findings included a small conoventricular type of VSD, a bilateral conus (subaortic and subpulmonary), subaortic stenosis, and preductal coarctation of the aorta.

Double-outlet right ventricle (DORV) with situs solitus of the viscera and atria, L-loop ventricles, and D-malposition of the great arteries, that is, DORV {S,L,D}, with right-sided juxtaposition of the atrial appendages (JAA), and concordant atrioventricular alignments and connections. (A) External frontal view. (B) Opened right atrium (RA) and tricuspid valve (TV). (C) Opened left-sided morphologically right ventricle (RV), giving origin to the widely patent outflow tract to the main pulmonary artery (MPA) and to the stenotic outflow tract leading to the ascending aorta (Ao). (D) The opened left atrium (LA) and the large secundum atrial septal defect (ASD II). (E) Left-sided LA opening into the right-sided morphologically left ventricle (LV). (F) Right-sided LV and the conoventricular type of ventral septal defect (VSD). There was a bilateral muscular conus (subpulmonary and subaortic). The subaortic part of the conus has been opened, making it possible to see the stenotic aortic outflow tract arising from the left-sided RV. In A, one can see that the right atrial appendage (RAA) and the left atrial appendage (LAA) are juxtaposed. Both lie to the right of the vascular pedicle, Ao to the right and MPA to the left. Thus, this right-sided JAA consists of dextromalposition of the LAA in visceroatrial situs solitus. In other words, it is the LAA that is malpositioned relative to the vascular pedicle, resulting in right-sided JAA. But the really rare and amazing finding is the presence of atrioventricular (AV) alignment concordance with AV situs discordance. The RA is aligned with and opens into the RV through the very inferior TV (B–C). The LA is aligned with and opens into the LV through a superior mitral valve (MV) (D–F). This is a very rare form of crisscross AV relations, rare because the TV is inferior and the MV is superior. Thus, there is AV alignment concordance: right-sided RA to left-sided RV (B–C) and left-sided LA to right-sided LV (D–F). But the atria are in situs solitus (A, B, D) and L-loop ventricles are present (A, C, D–F). The RV is left-handed (C) and the LV is right-handed (F). Thus, there is AV situs discordance: solitus atria with L-loop ventricles. To the best of our present knowledge, whenever there is incongruence or disharmony between AV alignment and situs concordance or discordance, there always has been JAA. We think that JAA is important in this respect because both the atrial segment and the ventricular segment of the heart are malpositioned, rarely making it possible for AV alignment and AV situs concordance and/or discordance to be opposites. When only one cardiac segment is malpositioned—typically the ventricular segment, and when one atrium opens into one ventricle, AV alignment and situs concordance or discordance are the same, not opposites. This is Dr. Henry Wagner’s case from Children’s Hospital in Buffalo, New York. We shall be forever indebted to him for having been so kind as to let us study and learn from this very rare case. AoV, aortic valve; IVC, inferior vena cava; FW, free well; Lt Innom V, left innominate vein; To Ao, to aorta; SVC, superior vena cava; VS, ventricular septum.

From Van Praagh R, David I, Gordon D, Wright GB, Van Praagh S. Ventricular diagnosis and VSD. In: Godman M, ed. Paediatric Cardiology. 1980, Edinburgh: Churchill Livingtone;1981:153, reproduced with permission.

But the most remarkable feature of this very rare case was the presence of concordant AV alignments and connections, despite the fact that the atria and the ventricles were discordant in terms of their segmental situs. The viscera and atria were in situs solitus, with the RA to the right and the LA to the left, that is, DORV {S,-,-}. L-loop or inverted ventricles were present, that is, DORV {S,L,-}. The morphologically RV was left-sided and left-handed. The morphologically LV was right-sided and right-handed.

But the AV alignments were concordant (not discordant, as expected): The right-sided RA was aligned with and ejected into the left-sided RV through the right-sided and inferior tricuspid valve. The left-sided LA was aligned with and ejected into the right-sided LV through the superior and left-sided mitral valve. The tricuspid valve opened inferiorly from right-to-left, and the mitral valve opened superiorly from left to right. Hence, crisscross AV relations were present, meaning that the AV inflow tracts from the atria into the ventricles were angulated relative to each other, rather than being approximately parallel to each other, which is normal (see Fig. 9.24 ).

How could situs solitus atria open into inverted (L-loop) ventricles in a concordant fashion—RA to RV and LA to LV? We think that the answer is that both the atrial segment and the ventricular segment were malpositioned. The presence of right-sided JAA indicates that the atria, although in situs solitus, were not entirely normally positioned. The ventricles were obviously malpositioned (L-loop ventricles).

When both the atrial and the ventricular segments are malpositioned, rare and surprising AV alignments and connections can occur. Usually, the atria are the “straight men”; they are normally positioned. Usually, it is only the ventricles that are malpositioned, the ventricles being “professional contortionists.” Usually, therefore, when the AV segmental anatomy is {S,L,-}, the AV alignments and connections are discordant (RA to LV and LA to RV) because only the ventricles are positioned abnormally. But when both the atrial and the ventricular segments are positionally abnormal, even though the AV segmental anatomy is {S,L,-}, the AV alignments and connections can be concordant, even though the situs (pattern of anatomic organization) of the atrial and ventricular segments is discordant.

The segmental anatomy of the conotruncal (infundibuloarterial) segment was D-malposition (aortic valve to the right of the pulmonary valve). Hence, the segmental anatomy was {S,L,D}. The ventriculoarterial alignments were those of DORV. Consequently, the segmental anatomy of this rare and fascinating case was DORV {S,L,D}—both great arteries arising above the left-sided RV.

As this rare case illustrates, there are two different kinds of concordance and discordance:

• 1.
  

  alignment concordance and discordance (the atrium is aligned with and opens into which ventricle?); and

  
  
• 2.
  

  situs concordance and discordance (what is the visceroatrial situs, and what is the ventricular situs or loop?).

Almost always, these two different types of concordance and discordance are the same, or congruent. For example, in typical congenitally physiologically corrected TGA, that is, TGA {S,L,L}, the AV alignments are discordant (RA to LV and LA to RV) and the pattern of AV situs is discordant {S,L,-}. Only rarely are AV alignment concordance/discordance and AV situs concordance/discordance opposites, or incongruent, as in this rare and instructive case of DORV {S,L,D} with AV alignment concordance and AV situs discordance (see Fig. 9.24 ).

Because AV segmental situs anatomy such as {S,D,-} and {S,L,-} does not predict AV alignments with 100% accuracy (because they are two different variables), whenever the AV alignments are different from what is usual, they must be specified. For example, typical congenitally physiologically corrected transposition may be represented as TGA {S,L,L}. If not otherwise specified, one may assume that the AV alignments are discordant: RA to LV and LA to RV. However, when this is not the case, the AV alignments and connections must be specified for clarity; that is, TGA {S,L,L} with double-inlet LV, with straddling tricuspid valve, with tricuspid atresia, with double-inlet RV, and so on.

Why is this necessary? Because, as this rare case of DORV {S,L,D} with AV alignment concordance but with AV situs discordance so clearly illustrates, AV alignment concordance/discordance and AV situs concordance/discordance are really two different variables that may be the same, or different.

Anomalous vein connecting umbilical vein with coronary sinus. A 10-day-old white boy (Case 364, A81-76) displayed a rare anomaly of systemic venous return. In addition to an ASD II (deficient septum primum), this patient had an anomalous vein connecting the umbilical vein with the coronary sinus via the right lobe of the liver. This anomalous vein also received a small hepatic vein. This patient was postmature (42 weeks gestation) and suffered from persistent fetal circulation. The pulmonary resistance was very elevated (systemic or suprasystemic). There was marked pulmonary arterial hypertension. The large PDA was closing. Congestive heart failure developed and the patient died.

This anomalous systemic vein connecting the umbilical vein with the coronary sinus via the right lobe of the liver was anatomically abnormal but physiologically normal in the sense that the umbilical venous blood returned normally to the RA.

Congenital mitral stenosis with absence of posteromedial papillary muscle of the LV: a rare form of parachute mitral valve. In typical parachute mitral valve with a divided AV canal (not with common AV canal), the anterolateral papillary muscle group is absent. The large posteromedial papillary muscle group receives all of the insertions of the chordae tendineae. However, in a 3-month-old white girl (Case 376, A82-26), a rare form of parachute mitral valve was found: the posteromedial papillary muscle group was absent, and the anterolateral group was well developed and received all of the mitral chordae tendinae. Hence, the papillary muscle architecture of this patient was the opposite of that which is usually seen in typical parachute mitral valve with a divided AV canal.

Interestingly, when the common AV canal is present, potentially parachute mitral valve (after surgical repair of the AV septal defect) is characterized by the same left ventricular papillary muscle architecture as was seen in this patient without a common AV canal: absence of the posteromedial papillary muscle and a large anterolateral papillary muscle of the LV receiving all of the mitral chordae tendinae.

This patient also had right-sided JAA {S,D,S}, which is characterized by left-sided obstructive lesions such as congenital mitral stenosis; whereas left-sided JAA ^, is frequently associated with right-sided obstructive anomalies such as tricuspid atresia or severe stenosis.

ASD II with primary pulmonary hypertension. A 2 7/12-year-old white boy (Case 391; A82-145) with pectus excavatum presented with failure to thrive and was found to have severe pulmonary hypertension of unknown cause. He developed congestive heart failure, pleural effusions (right, 50 mL and left, 10 mL), bilateral pulmonary congestion and hemorrhages, and ascites (55 mL) that led to death. Autopsy revealed a secundum ASD consisting of three fenestrations of the septum primum, one measuring 7 × 5 mm and the other two having diameters of 1 to 2 mm. The surprising findings were those indicative of primary pulmonary hypertension: decreased intra-acinar arteries and arterioles, increased connective tissue around larger vessels, medial hypertrophy, intimal proliferation, angiomatoid and plexiform lesions, periarteritis, and large vessel necrotizing arteritis.

Raghib Syndrome Without a Large Low Posterior Interatrial Communication

When a persistent LSVC opens into the LA because of a coronary sinus septal defect, almost always there is a large low posterior opening in the atrial septum that has been interpreted as an enlarged right atrial ostium of the unroofed coronary sinus; this combination of anomalies is known as the Raghib syndrome. However, in Case 397 (C82-96), a boy with a large ASD II (deficiency of the septum primum) had a persistent LSVC that opened into the LA because of a large coronary sinus septal defect. The fascinating finding was that this 19-week fetus did not have an enlarged right atrial ostium of the coronary sinus. Instead, this ostium was of normal size.

We are aware of no developmental hypothesis to explain this observation. Suffice it to say that it is rarely possible for a persistent LSVC to drain to the LA, apparently because of a coronary sinus septal defect, without a large low posterior interatrial communication.

It may be relevant to record that this fetus had a 42-year-old mother and that this fetus had trisomy-13 with polydactyly (six digits on both hands), a very small membranous VSD, and bilaterally trilobated lungs (with a normally formed spleen).

So, the answer to the question, Does the Raghib syndrome always have a large low posterior interatrial communication? is almost always, but not always, as this rare case demonstrates.

Does a rare form of cor triatriatum, consisting of a prominent interseptovalvular space, really exist? There has been considerable uncertainty about this, which is why this “theoretical” form of cor triatriatum is usually omitted from standard textbook accounts. The interseptovalvular space, which is well seen in the human embryo (please see Chapter 2 ), is the space between the septum primum to the left and the left venous valve to the right. Usually this space is largely or totally obliterated.

But rarely, the interseptovalvular space can persist, as in Case 403 (C82-350). The patient was a 55-year-old white man with a large ASD II, TGA {S,L,L}, and tricuspid atresia (left-sided). He also had severe mitral regurgitation (right-sided), atrial flutter, chronic congestive heart failure, and a systemic level of pulmonary hypertension without pulmonary regurgitation. The immediate cause of death was aspiration.

In addition to the foregoing, autopsy also revealed atherosclerosis of the pulmonary arterial tree (Heath-Edwards grade 3 changes), multiple fenestrations of the right-sided mitral valve (a rare finding), and evidence of multiple old brain abscesses.

This patient had cor triatriatum (a heart with three atria) in the following sense. The morphologically RA was right-sided. The morphologically LA was left-sided. There was a third space at the atrial level, between the right-sided RA and the left-sided LA. This third atrial space was bounded by the septum primum to the left and by a prominent left venous valve to the right, that is, the interoseptovalvular space. The ISVS (interseptovalvular space) received no pulmonary or systemic vein and hence was of no clinical or pathophysiologic significance.

The point of knowing about this rare form of cor triatriatum is understanding, that is to know what one is dealing with and not to undertake any unnecessary interventional or surgical steps.

Truncus arteriosus type B1, that is, with intact ventricular septum (type B) and with aortopulmonary septal remnant (type 1). Case 407 (C82-471) had a secundum ASD because of the presence of a valve-incompetent PVO (the ASD measuring 5 × 2 to 3 mm). This was a consult that was received in 1982; unfortunately we do not know the sex of the patient or the age at death. This was the first case of truncus arteriosus type B1 ^8,9 that I had ever seen. There was no VSD; the membranous septum was large and intact. The aortopulmonary window component was small because the aortopulmonary septal remnant was quite well developed. The truncal valve was quadricuspid, the semilunar valves were in common, and the pulmonary valve leaflets were myxomatous. In 1982, we were excited to have discovered truncus arteriosus type B1. Up to that time, types B2 and B4 ^8,9 had been reported but not type B1.

Incompletely common AV canal with imperforate Ebstein anomaly. Case 440 was a consult that we received in 1984 (C84-34). Unfortunately, the patient’s sex, race, and age at death are unknown to us. There was a large ASD II, with only a few strands of septum primum being present. This patient had the very rare combination of incompletely common AV canal (with an ostium primum type of ASD, an incompletely cleft anterior leaflet of the mitral valve, and an intact ventricular septum) and an imperforate Ebstein anomaly of the tricuspid valve. This patient also had severe valvar pulmonary stenosis and a persistent LSVC to the coronary sinus to the RA.

The incomplete form of common AV canal with Ebstein malformation is a rare combination of anomalies that was also found in a 2-month-old white girl (Case 506, C88-178, a consult from Dr. Dominique Metras of Marseilles, France). This patient had an unusual form of tricuspid atresia type Ib, the severe subpulmonary stenosis being produced by a tiny conoventricular type of VSD. In addition to the imperforate Ebstein anomaly, there was partial absence of the tricuspid valve leaflets. The septal leaflet was absent, and the posterior leaflet was almost totally absent. The anterior tricuspid leaflet was deep, curtain-like, and totally obstructive. There was Uhl disease of the right ventricular free wall. The LV had a bizarre “wrap-around” shape because it wrapped around the hypoplastic and dysplastic RV. Ebstein malformation is an anomaly not only of the tricuspid valve but also of the RV.

Right aortic arch without mirror-image branching of the brachiocephalic arteries. How is this possible? This occurs when both common carotid arteries arise from the right aortic arch but both subclavian arteries originate from the descending thoracic aorta (Case 443, A85-6, a 1-day-old white boy).

Congenital stenosis of the IVC at its junction with the RA. A 6-day-old white boy (Case 501, A88-72) with a secundum ASD (a sprung PFO with an aneurysm of the septum primum bulging into the RA) and aortic valvar atresia with an intact ventricular septum had large coronary-to–left ventricular sinusoids. There was a right coronary artery-to–left ventricular sinusoid inferiorly that measured 2 to 3 mm in diameter. A left anterior descending coronary artery–to–left ventricular sinusoid was 2 mm in diameter. There was also a sinusoid between the left circumflex coronary artery and the LV. These coronary arteries also displayed the typical coronary arteriopathy at their junction with these large sinusoids: coronary mural thickening and luminal narrowing.

Probably the most unusual finding in this case was severe congenital stenosis of the IVC at its junction with the RA. The lumen of the IVC at the IVC-RA junction measured less than 1 mm in diameter, which is an extraordinarily rare finding.

Stenosis of the right atrial ostium of the coronary sinus with a decompressing “snowman” pathway. A 3-month-old white boy (Case 525, A90-64) with a large secundum ASD had TGA {S,D,D} with a subpulmonary conoventricular type of VSD. However, the rare finding was marked stenosis of the right atrial ostium of the coronary sinus, with dilatation of the coronary sinus. A small persistent LSVC connected the obstructed coronary sinus to the left innominate vein and then to the right SVC and RA, constituting a compressing snowman type of venous pathway reminiscent of the supracardiac form of TAPVC but without TAPVC. The pulmonary veins were normally connected. This patient also had double-orifice mitral valve (DOMV) with a large central tongue of fibrous tissue resulting in an unusual form of congenital mitral stenosis.

Triple-outlet RV (TORV). How is it possible to have triple -outlet RV? The answer is in conjoined twins. This very rare anomaly was found in Case 556 (C91-146), a female white fetus (gestational age unknown to us) with a secundum type of ASD (multiple fenestrations in the septum primum). These conjoined twins had two heads, but only one body with two feet and two arms. The Latin term for this is dicephalus dipus dibrachius (two heads, two feet, two arms). The right twin had DORV {S,D,D} with pulmonary outflow tract stenosis and interrupted aortic arch type B. The left twin had normal segmental anatomy {S,D,S}. The two SVCs both connected with the RA. There was only one IVC that also connected with the RA.

Two coni arose above the one right ventricular sinus. The right conus gave rise to both great arteries of the right-sided twin, resulting in the right-sided twin’s DORV {S,D,D}. The left-sided conus gave origin to the normally related and connected pulmonary artery of the left-sided twin. The aorta of the left-sided twin was normally related and connected with the LV, with aortic-mitral fibrous continuity.

The LV supplied only the left-sided twin. The RV supplied the head and neck of the right-sided twin and the pulmonary artery of the left-sided twin.

Thus, the TORV consisted of both great arteries of the right-sided twin, who had DORV {S,D,D}, and the pulmonary artery of the left-sided twin, who had {S,D,S}. To the best of our present knowledge, it is impossible for one individual (homo sapiens sapiens) to have TORV. In humans, this can occur only in conjoined twins.

However, TORV perhaps may occur in the higher reptilia such as alligators and crocodiles, because three great arteries normally occur in these life forms. They normally have a right ventricular pulmonary artery, a right ventricular aorta, and a left ventricular aorta. We are not aware that TORV has been documented in higher reptiles.

Familial TOF and truncus arteriosus. A 15-month-old white girl with a large ASD II (Case 563, A92-31) had TOF {S,D,S} (or pentalogy of Fallot) with pulmonary infundibular and valvar atresia with multiple aortopulmonary collateral arteries (MAPCAs). An older sibling of this patient had truncus arteriosus. Both patients were the products of a consanguineous (first-cousin) marriage.

This type of familial congenital heart disease—tetralogy and truncus in siblings—supports the concept that tetralogy with pulmonary outflow tract atresia and truncus arteriosus are closely related anomalies anatomically, embryologically, and genetically.

This patient also illustrated a very practical surgical lesson. At 15 months of age, it was decided that this patient needed a change of her RV-to–pulmonary artery conduit because of the development of a 65–mm Hg gradient across the conduit. Most of the conduit was removed, except for its right ventricular origin and its pulmonary artery insertion. The patient could not be weaned from cardiopulmonary bypass, leading to death. Autopsy revealed severe obstructions at the conduit-to–right pulmonary artery junction and at the conduit-to–left pulmonary artery junction. The therapeutic lesson of this case was to replace the whole conduit, not just the middle part of it, even when the conduit narrowing may appear to be maximal in its central portion, rather than at its proximal or distal end. Conduit neopseudointimal lining or peel can detach from the conduit and embolize, resulting in a serious or fatal pulmonary embolus. Conduit “peel” is well named: it can and does and should never be “trusted.” The treacherous nature of conduit peel should be borne in mind during and after interventional conduit dilations and stenting.

Absence of the main pulmonary artery, right pulmonary artery, left pulmonary artery, and ductus arteriosus does occur. A 7-hour-old white girl with a small secundum ASD caused by an abnormally short and thin septum primum (Case 571, A92-80) had multiple congenital anomalies and TOF {S,D,S} (or pentalogy of Fallot, a term that we really do not use very much, although everyone knows what it means) with pulmonary outflow tract atresia and absence of the main pulmonary artery, right pulmonary artery, left pulmonary artery, and ductus arteriosus. This patient had absence of the left lung and left pulmonary vein. The persistent LSVC connected with the coronary sinus and emptied into the RA. The left innominate vein was absent, which is not surprising because there were bilateral SVCs. A solitary collateral artery from the descending thoracic aorta supplied the right lung.

Why is this case noteworthy? One reason is that it proves that Collett and Edwards truncus arteriosus type IV does indeed exist. There has been much uncertainty about this question. Indeed, Dr. Jesse Edwards renounced his truncus arteriosus communis type IV, not because it was illogical, but because he was not certain that this anomaly (no matter what one may prefer to call it) in fact exists. We shared Dr. Edwards’ concern about the possible nonexistence of his type IV truncus arteriosus communis. As this case proves, although exceedingly rare, this anomaly does indeed exist.

Additional anomalies included absence of the right coronary arterial ostium, that is, a single left coronary artery; anophthalmia, bilateral (no eyes); dysmorphic Potter syndrome–like facies with a broad flat nose and high nasal bridge; flat malformed helices of the ears with paucity or absence of helical cartilage; renal dysplasia; persistent urogenital sinus; ureterovesicle stenosis; and uterine atresia with atresia of the Fallopian tubes.

TOF {I,D,S}. A 6-month-old Asian girl (Case 573, A92-94) with a secundum ASD (enlarged ostium secundum above the septum primum measuring 7 × 4 mm, and a fenestration within the septum primum measuring 6 × 4 mm) had a rare form of tetralogy (or pentalogy) of Fallot with interesting and unusual segmental anatomy: visceroatrial situs inversus { I, -,-} , with discordant D-loop ventricles {I, D ,-} and concordant solitus normally related great arteries {I,D, S } that were also afflicted with TOF with infundibular and valvar pulmonary atresia. The circulations (pulmonary and aortic) were physiologically uncorrected (“complete” transposition-like) because of the presence of one intersegmental discordance (AV). This physiologic uncorrection of the circulations was further exacerbated by the coexistence of pulmonary infundibular and valvar atresia. The main pulmonary artery was absent, but the right and left pulmonary artery branches were in continuity. The aortic arch was left-sided (abnormal for visceroatrial situs inversus) and there was a right-sided PDA or ductus-like collateral. A portion of the anterolateral papillary muscle of the LV arose from the left ventricular septal surface and was associated with an anterolateral commissural cleft of the mitral valve with mitral regurgitation. The ostium of the left coronary artery was absent, resulting in a single right coronary artery.

Therapeutically, at 4 days of age a modified right Blalock-Taussig anastomosis was successfully performed. At 6 months of age, a cardiac catheterization was complicated by the rupture of a balloon at the catheter tip, releasing carbon dioxide into the LV. Hypotension and complete heart block followed, leading to death despite all resuscitative efforts. Autopsy confirmed the previously mentioned diagnoses and revealed the presence of a right-sided spleen (usual for visceroatrial situs inversus). Histologic examination revealed minor ventricular myocardial contraction band necrosis.

What are the most important lessons of this case? First, it is important to know that TOF can have rare segmental anatomy. Tetralogy is not always TOF {S,D,S} or TOF {I,L,I}. Like TGA, normally related great arteries complicated by TOF can occur with both concordant and discordant AV alignments. Second, it is important to realize that the intracardiac rupture of a balloon, even though filled with carbon dioxide, is not necessarily an innocuous event.

Pulmonary valvar atresia with a small membranous VSD, which is not TOF, does exist. When the great arteries are essentially normally related, and there also is pulmonary valvar atresia and a VSD, nearly always the patient has the worst form of TOF (tetralogy with pulmonary atresia). Rarely, the patient can have pulmonary valvar atresia (or stenosis), with a normally formed subpulmonary conus, without the anterosuperior conal septal malalignment that characterizes both TOF and the Eisenmenger complex. A 2-month-old Japanese boy (Case 582, C92-356) illustrated this point. The patient had valvar pulmonary atresia {S,D,S} with a normal subpulmonary conus and a small high subaortic membranous VSD.

This patient also had a prominent left venous valve forming a rete Chiari within the RA. Almost always it is the right venous valve that forms a rete Chiari. The unusually large left venous valve also resulted in a prominent interseptovalvular space, that is, an unusually well-demarcated space between the septum primum to the left and the left venous valve to the right. This unusually well-seen interseptovalvalar space can also create the impression of a rare form of cor triatriatum but without pulmonary (or systemic) venous obstruction because no pulmonary or caval vein drains into the interseptovalvular space.

But the salient lesson of this case is that pulmonary valvar atresia with a VSD is not always a tetralogy-atresia.

Asplenia with interrupted IVC. Almost always the IVC is intact (not interrupted) in visceral heterotaxy with asplenia. By contrast, interruption of the IVC is characteristic of visceral heterotaxy with polysplenia (see Chapter 29 ). Rarely, however, interruption of the IVC can occur in the asplenia syndrome, as in Case 595 (C93-135), a 5-day-old boy with dextrocardia and DORV {A(I),D,D} with pulmonary atresia. {A(I),D,D} briefly indicates the segmental anatomy. There was situs ambiguus of the viscera, which is typical of the asplenia syndrome, that is { A ,-,-}, the atria probably being in situs inversus, that is {A (I) ,-,-}. There were D-loop ventricles, that is {A(I), D ,-}; hence, there was probably AV discordance. The great arteries were in D-malposition, that is {A(I),D, D }. The ventriculoarterial alignments were those of DORV. Hence, the segmental anatomic set was DORV {A(I),D,D}. DORV is typical of the asplenia syndrome. DORV is a short form for “origin of both great arteries above the right ventricle,” whether both great arteries are patent or not. In this patient, there was pulmonary outflow tract atresia, also frequent with the asplenia syndrome. So, DORV with pulmonary atresia really is not a contradiction in terms, even though that may be one’s initial impression, because of what DORV really means.

This patient had an enlarged azygos vein connecting with the right SVC. The enlarged azygos vein, typically associated with interruption of the IVC, is often called an azygos extension . This designation may suggest to the uninitiated that there is something unusual about such an azygos extension. In fact, an azygos vein is a normal part of the systemic venous return. The only unusual feature of an azygos extension is its large size. With interruption of the IVC from the renal veins to the hepatic veins, the azygos vein must be much larger than it normally is in order to convey the systemic venous return from the lower body to a SVC and then to the RA.

The suprahepatic segment of the IVC, which is present in interruption of the IVC, connected with the left-sided atrium, strongly suggesting that the morphologically RA was left-sided. The connection of the IVC is one of the most highly reliable diagnostic markers of the RA because the RA consists in part of the systemic venous confluence. This connection of the suprahepatic segment of the IVC with the left-sided atrium is one of the reasons that we thought that the RA was left-sided and hence that there probably was situs inversus of the atria. We say “probably” because of the coexistence of visceral heterotaxy.

Another highly reliable diagnostic marker of the RA is the ostium of the coronary sinus. However, this structure is often absent in the asplenia syndrome, as it was in this patient.

The pulmonary veins often are of no help in identifying the atria in the heterotaxy syndrome with asplenia because they frequently have a totally anomalous connection, as they had in this patient: TAPVC below the diaphragm with obstruction.

The small right-sided PDA was almost closed, this being the cause of the patient’s death at 5 days of age.

This unusual case indicates that, rarely, interruption of the IVC can occur in association with the asplenia syndrome.

Primary hypoplasia of the RV. Primary right ventricular hypoplasia is an unfamiliar diagnosis, perhaps because right ventricular hypoplasia usually is (or appears to be) secondary to pulmonary valvar stenosis or atresia, tricuspid stenosis or atresia, or some combination of the foregoing. Occasionally, however, primary right ventricular hypoplasia occurs, that is, right ventricular hypoplasia without tricuspid or pulmonary valvar stenosis or atresia. This unusual finding was observed in Case 592, a 3-month-old white boy with multiple secundum ASDs: an enlarged ostium secundum above the free edge of septum primum (5 mm in diameter) and three fenestrations within the septum primum (4, 3, and 2 mm in diameter). This patient with a small RV also had right ventricular endocardial sclerosis for reasons unknown. We make the diagnosis of endocardial sclerosis (as opposed to endocardial fibroelastosis ), when there is mild to moderate thickening and whitening. (We make the diagnosis of endocardial fibroelastosis when the thickening and whitening is marked, clear-cut, and striking.) This patient did not have Uhl disease; there was not a paucity or absence of right ventricular free wall myocardium. Instead, the RV was curiously small, with mild endocardial thickening and whitening, for no obvious reason. Hence, we regarded the RV hypoplasia as primary (i.e., idiopathic, not secondary to any known cause).

From the management viewpoint, this patient, who had normal segmental anatomy, that is, {S,D,S}, was treated with a modified right Blalock-Taussig anastomosis (3.5 mm in diameter) at 5 days of age. Postoperatively, he developed supraventricular tachycardia. This patient had no obstructive right heart lesion, except perhaps the small RV. Thinking that the modified right Blalock-Taussig anastomosis was excessive, it was decided to perform a bidirectional Glenn anastomosis, with occlusion of the Blalock Taussig anastomosis, at 2¾ months of age. Postoperatively, there was SVC obstruction followed by thrombosis, leading to death.

This unusual case of primary right ventricular hypoplasia raised a number of difficult management issues:

• 1.
  

  When there is no obstructive right heart lesion and no VSD and a secundum ASD permitting right-to-left shunting apparently because of a small RV, a modified Blalock-Taussig anastomosis in the first week of life may not be indicated.

  
  
• 2.
  

  How early can one do a bidirectional Glenn procedure? We usually say about 6 months of age, or perhaps a bit earlier. But 2¾ months of age may well have been too early.

  
  
• 3.
  

  Suffice it to say that the management of primary right ventricular hypoplasia with a secundum ASD is much more difficult than one might at first appreciate. “Masterful inactivity” may be the optimal therapeutic plan.

I will never forget the case of a colleague from the Johns Hopkins Hospital who had a patient in her 20s with this rare and poorly understood diagnosis. She was mildly cyanotic because of right-to-left atrial shunting. But she managed this problem with “creative makeup.” Finally, she and her physicians wanted to fix her, to make her normal. So they surgically closed her large secundum ASD. The result was disastrous. She went into severe right heart failure and almost died. Fortunately, her surgeon reoperated and removed the ASD patch, and the patient recovered and resumed her mildly cyanotic but generally quite satisfactory life.

Now, I know very well that one or two cases prove nothing. I agree that “one mouse is no mouse.” But still, when dealing with a patient with the rare and poorly understood diagnosis or primary right ventricular hypoplasia, remembering this cautionary tale may help save the patient’s life. The management of this rare entity is much more subtle and difficult that it may at first appear.

The therapeutic problem appears to be as follows:

• 1.
  

  There is no cure for primary right ventricular hypoplasia (at the present time).

  
  
• 2.
  

  Palliation, such as a modified Blalock-Taussig anastomosis or a bidirectional Glenn procedure, may well not succeed, as our patient illustrates.

  
  
• 3.
  

  Closure of the secundum ASD may not be tolerated. If a patient shunts right to left through a secundum ASD in association with primary right ventricular hypoplasia, such a patient may have to shunt right to left to maintain adequate systemic cardiac output and closure of the secundum ASD may be contraindicated.

Needless to say, I very much hope that this therapeutic problem will be recognized and solved. But for now, sailor beware.

Primary endocardial fibroelastosis (EFE) of the RV. Right ventricular EFE with an intact ventricular septum almost always is secondary to pulmonary valvar atresia or severe stenosis. Primary EFE of the RV, not secondary to pulmonary valve obstruction or any other identified disease process, is very rare indeed. This disease was found in an 18-day-old boy (Case 612, A95-83). He had a moderately large secundum ASD (12 × 6 mm). The patient had right ventricular endomyocardial disease with marked EFE of the RV and mild endocardial sclerosis of the LV. The segment anatomy was normal, that is {S,D,S}, the pulmonary valve was unremarkable, and a very careful autopsy revealed no evidence of pheochromocytoma or other significant pathologic condition. Thus, this biventricular endomyocardial disease was, and is, an enigma.

Truncus arteriosus with single LV. A 3-week-old boy (Case 613, C95-364) with a large secundum ASD (18 × 9 mm with multiple fenestrations in a deficient septum primum) had truncus arteriosus type A2 (type A = VSD or bulboventricular foramen present; type 2 = no aortopulmonary septal remnant) with normal segmental anatomy ({S,D,S}), dextrocardia, left-sided JAA, extreme tricuspid stenosis (1 mm in diameter), double-inlet LV, single LV (right ventricular sinus absent), infundibular outlet chamber, and congenital absence of the ductus arteriosus. Truncus arteriosus and single LV with an infundibular outlet chamber constitute a rare combination of congenital heart disease.

Left-sided JAA syndrome. A 28-year-old-man (Case 624, MR 33) with a very large secundum type of ASD (multiple fenestrations in the septum primum resulting in a functionally common atrium) displayed the syndrome of left-sided JAA ^, : tricuspid atresia, large ASD II, VSD (high, large, conoventricular type), TGA {S,D,D}, pulmonary stenosis (subvalvar and valvar), and dextrocardia. Many still do not know that there is a left-sided JAA syndrome ^, and a right-sided JAA syndrome. The left-sided JAA syndrome ^, is characterized by right heart obstructive lesions such as tricuspid atresia, as in this patient. Conversely the right-sided JAA syndrome frequently has obstructive left heart anomalies such as congenital mitral stenosis. This 28-year-old man is one of the oldest patients known with the left-sided JAA syndrome.

Complete form of common AV canal with imperforate Ebstein anomaly, double-orifice of potential mitral valve, and incomplete cleft of the potential mitral valve. An 18-hour-old white girl (Case 630, MR 45) with Down syndrome had a large ASD II because of a defective septum primum. In addition to the previously mentioned anomalies, she had a small VSD of the AV canal type beneath the posteroinferior leaflet of the common AV valve. This case illustrates that completely common AV canal can be much more complex than most classifications suggest.

Infantile Marfan syndrome. Case 639 (C94-26) was a 3-month-old boy with infantile Marfan syndrome. In addition to a secundum type of ASD (two fenestrations in the septum primum, 7 × 4 mm and 4 × 2 mm), this patient had massive cardiomegaly (72 g/28 to 38 g, which is normal). There was hypertrophy and enlargement of all cardiac chambers. The tricuspid valve had a circumference of 79 mm/28 to 32 mm (normal). The mitral valve had a circumference of 73 mm/29 to 37 mm (in normal controls). The pulmonary valvar annulus was very dilated (19 mm in diameter), as was the aortic valvar annulus (13.5 to 15 mm in diameter). There was myxomatous thickening and redundancy of the mitral and tricuspid leaflets, with marked elongation of the chordae tendineae. There was prominent dilatation of the aortic and pulmonary roots. The heart of a typical patient with infantile Marfan syndrome (not Case 639) is presented in Fig. 9.25 , illustrating many of the features mentioned previously.

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