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Isolated infundibuloarterial inversion and fifth aortic arch in an infant: a newly recognized cardiovascular phenotypes with chromosome 22q11 deletion
International Journal of Cardiology 71 (1999) 89–91 www.elsevier.com / locate / ijcard
Letter to the Editor
Isolated infundibuloarterial inversion and fifth aortic arch in an infant: a newly recognized cardiovascular phenotypes with chromosome 22q11 deletion a, b c d e Meng-Luen Lee *, Ing-Sh Chiu , William Fang , Shyh-Jye Chen , Yu-Mei Wang , f Wun-Tsong Chaou a
Department of Pediatrics, Division of Pediatric Cardiology and Director of Pediatric Intensive Care Unit, Changhua Christian Hospital, Changhua 50050, Taiwan b Department of Surgery, Division of Cardiovascular Surgery, College of Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan c Department of Pediatrics, Laboratory of Medical Genetics, Changhua Christian Hospital, Changhua 50050, Taiwan d Department of Medical Imaging, College of Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan e Department of Pediatrics, Division of Pediatric Endocrinology and Metabolism, Changhua Christian Hospital, Changhua 50050, Taiwan f Department of Pediatrics, Division of Pediatric Neurology and Head, Changhua Christian Hospital, Changhua 50050, Taiwan Received 22 March 1999; received in revised form 17 May 1999; accepted 4 June 1999
To the Editor: Conotruncal and arch artery anomalies have been well known for their frequent association with chromosome 22q11 deletion [1]. We have encountered a newly recognized cardiovascular phenotypes of isolated infundibuloarterial inversion [2] and a fifth aortic arch in an 11-month-old infant who had chromosome 22q11 deletion. An 11-month-old female infant was found to have lip cyanosis, tachycardia, and tachypnea since birth. There was a grade III / VI systolic ejection murmur heard over the bilateral middle sternal border in the 4th intercostal space at birth. A tentative diagnosis of double outlet right ventricle with subaortic ventricular septal defect and pulmonary stenosis was made echocardiographically. She was first admitted due to acute cardiopulmonary distress and seizure at 11 months of age. On physical examination, she was underweight (5.3 kg ,3 percentile), and was looked *Correspondence author. Tel.: 00-886-4-7238595 Ext: 7442; fax: 00886-4-7238847 or 00-886-4-7232942.
acutely ill with acrocyanosis, tachycardia (160 beats / min), and tachypnea (48 breaths / min). The breathing sound was diminished in the left lung field. There was a grade IV/ VI systolic ejection murmur over bilateral middle sternal border. Liver was palpable 5 cm below the right costal margin. Plain chest film and pleural echography suggested massive pleural effusion. Chest tube insertion revealed milky pleural effusion, which is characterized by increased lymphocyte counts (10,514 / mm 3 ) and increased triglyceride level (1,932 mg / dL). The congenital chylothorax was further treated by a pleural-peritoneal shunt, total parenteral nutrition, and then elementary milk supplemented with medium-chain triglycerides. The second and third hospitalizations were related to generalized tonic-clonic seizure and recurrent pneumonia. Calcium levels and immune studies were within normal limits. No evidence of primary immunodeficiency syndrome can be ascribed to. Refractory wheezing, stridor, and fever prompted the fourth hospitalization, during which time bacteremia (Streptococcus viridans) with pneumonia intervened. Wheeze and stridor still lingered despite a complete
0167-5273 / 99 / $ – see front matter 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 99 )00099-6
90
M.-L. Lee et al. / International Journal of Cardiology 71 (1999) 89 – 91
hS,D,Ij, subvalvular and supravalvular pulmonary stenosis, left pulmonary artery stenosis, a right aortic arch, an aberrant left subcalvian artery, and a single coronary artery from the anterior coronary cusp. Electron beam CT or ultrafast CT showed bronchial compression associated with isolated infundibuloarterial inversion and a fifth aortic arch (Fig. 1). At surgery, a complete vascular ring, which was composed of an aberrant left subclavian artery arising from a right arch and giving off a left ligamentum arteriosum to the juxtaductal stenotic left pulmonary artery, was visualized to impinge on the trachea, esophagus, and thoracic duct. A left-sided ligamentum arteriosum was divided to release the tension. A remnant of nonpatent fifth aortic arch, of systemic-tosystemic type, was identified and divided at surgery. The ascending aorta was mobilized and fixed to the sternocostal junction to release tension on the bronchi. She survived a surgical repair of the isolated infundibuloarterial inversion without the use of an extracardiac conduit [3]. The abnormal facies, which bear a resemblance to those of DiGeorge syndrome, and cardiac malformations prompted a chromosome study of 22q11 microdeletion (Fig. 2). She was free of wheezing respiration in a 2-year follow-ups. A lot of cardiovascular malformations, including
Fig. 1. Electron beam CT, right anterior oblique view 158, showed bilateral bronchial stenosis in association with isolated infundibuloarterial inversion and fifth aortic arch. Top: Prior to operation, bilateral bronchi were stenotic and compressed (stars) anteriorly by the right pulmonary artery coursing horizontally. Bottom: The aortic valve of aortic root (arrowhead) was found lying left, posterior, and inferior to the main pulmonary artery (asterisk), which implies presence of inverted normally related great arteries in isolated infundibuloarterial inversion hS,D,Ij. In addition, a remnant of fifth aortic arch (double-headed arrow) was identified.
course of intravenous antibiotics. Echocardiography, cardiac catheterization and angiocardiography showed situs solitus of the viscera and atria, d-loop ventricle, malalignment conoventricular septal defect, ventriculoarterial concordance with levo-posterior aorta, i.e., isolated infundibuloarterial inversion
Fig. 2. Fluorescent in situ hybridization (FISH) study showed chromosome 22q11 microdeletion using Oncor N25 probe. Arrowhead indicates 4 (2 green and 2 red) fluorescein signals in normal chromosome 22. Arrow identifies microdeletion of chromosome 22q11, with only 2 bright green signals.
M.-L. Lee et al. / International Journal of Cardiology 71 (1999) 89 – 91
inflow, outflow, and aortic arch arteries anomalies, can be induced by removal of the cardiac neural crest [4]. Isolated infundibuloarterial inversion (malalignment VSD and infundibular pulmonary stenosis) or inverted tetralogy of Fallot hS,D,Ij [2,3] can be regarded as a phenotype of cardiac outflow tract anomalies, according to the papers described Kirby ML et al. [4]. From the embryologic viewpoint, the role of cardiac neural crest for the conotruncal cardiac anomalies of interrupted aortic arch type B, truncus arteriosus, and tetralogy of Fallot in DiGeorge syndrome [5], velocardiofacial syndrome [6], and conotruncal anomaly face syndrome [7] cannot be overemphasized. From the genetic viewpoint, these conotruncal cardiac anomalies have been well known for their frequent association with chromosome 22q11 deletion in patients with DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome [1,7–9]. It is not far fetched to consider that chromosome 22q11 microdeletion may cause abnormality of the neural crest cells, which renders possible varied cardiac and noncardiac malformations in the above syndromes. There are two types of connection presented as either systemic-to-systemic or systemic-to-pulmonary artery conduits, if the fifth aortic arch persisted [10]. There was one report of tetralogy of Fallot in linkage with persistent fifth aortic arch [11]. Persistent fifth aortic arch can be seen after neural crest ablation in the chick (by letter communication with Kirby ML). It is still unknown that persistent fifth aortic arch, in human being, should be regarded as a member of abnormal patterning of the aortic arch arteries due to abnormality of the neural crest cells. Another interesting report is the finding of chromosome 22q11.2 deletion in a 16-year-old boy with cervical aortic arch, which is believed to arise as a result of a persistent third dorsal arch that reroutes the aortic arch into the cervical region [12]. There was a report of persistent fifth aortic arch in a 2-year-old girl, who presented hypertelorism and small epicanthal fold with hypoplasia of palpebral tissue and flat nasal bridge, and low-set ears with abnormal folds [13]. The facial anomalies in this patient mimicked those described in patients with DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome [7–9]. Patterning of all of the aortic arch vessels is disrupted after neural crest ablation. It seems that the neural crest cells carry instructions for
91
normal patterning for each species. We agree that abnormal patterning of this whole region is possible in the absence of neural crest (by letter communication with Kirby ML). We believe that 22q11 deletion may be associated with defective neural crest development. An experimental model of an animal with altered expression of the 22q11 candidate genes may tell us in the future for sure that this cascade of molecular biology works, i.e., gene 22q11 microdeletion can cause defective or abnormal neural crest cell development and then cardiovascular dysmorphogenesis. To the best of our knowledge, this is the first report of isolated infundibuloarterial inversion and fifth aortic arch associated with 22q11 microdeletion in the English literature.
References [1] Goldmuntz E, Clark BJ, Mitchell LE et al. Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol 1998;32:492–8. [2] Foran RB, Belcourt C, Nanton MA et al. Isolated infundibuloarterial inversion hS,D,Ij: a newly recognized form of congenital heart disease. Am Heart J 1988;116:1337–50. [3] Santini F, Jonas RA, Sanders SP, Van Praagh R. Tetralogy of Fallot hS,D,Ij: successful repair without a conduit. Ann Thorac Surg 1995;59:747–9. [4] Kirby ML, Waldo KL. Role of neural crest in congenital heart disease. Circulation 1990;82:332–40. [5] Van Mierop LHS, Kutsche LM. Cardiovascular anomalies in DiGeorge syndrome and importance of neural crest as a possible pathogenetic factor. Am J Cardiol 1986;58:133–7. [6] McLean SD, Saal HM, Spinner NB, Emanuel BS, Driscoll DA. Velo-cardio-facial syndrome. Am J Dis Child 1993;147:1212–6. [7] Momma K, Kondo C, Matsuoka R. Tetralogy of Fallot with pulmonary atresia associated with chromosome 22q11 deletion. J Am Coll Cardiol 1996;27:198–202. [8] Driscoll DA, Budarf ML, Emanuel BS. A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11. Am J Hum Genet 1992;50:924–33. [9] Goldberg RB, Motzkin B, Marion R, Scambler PJ, Shprintzen RJ. Velo-cardio-facial syndrome: a review of 120 patients. Am J Med Genet 1993;45:313–9. [10] Gerlis LM, Dickinson DF, Wilson N, Gibbs JL. Persistent fifth aortic arch. A report of two new cases and a review of the literature. Int J Cardiol 1987;16:185–92. [11] Donti A, Soavi N, Sabbatani P, Picchio FM. Persistent left fifth aortic arch associated with tetralogy of Fallot. Pediatr Cardiol 1997;18:229–31. [12] Kazuma N, Murakami M, Suzuki Y, Umezu R, Murata M. Cervical aortic arch associated with 22q11.2 deletion. Pediatr Cardiol 1997;18:149–51. [13] Lawrence TYK, Stiles QR. Persistent fifth aortic arch in man. Am J Dis Child 1975;129:1229–31.
Letter to the Editor
Isolated infundibuloarterial inversion and fifth aortic arch in an infant: a newly recognized cardiovascular phenotypes with chromosome 22q11 deletion a, b c d e Meng-Luen Lee *, Ing-Sh Chiu , William Fang , Shyh-Jye Chen , Yu-Mei Wang , f Wun-Tsong Chaou a
Department of Pediatrics, Division of Pediatric Cardiology and Director of Pediatric Intensive Care Unit, Changhua Christian Hospital, Changhua 50050, Taiwan b Department of Surgery, Division of Cardiovascular Surgery, College of Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan c Department of Pediatrics, Laboratory of Medical Genetics, Changhua Christian Hospital, Changhua 50050, Taiwan d Department of Medical Imaging, College of Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan e Department of Pediatrics, Division of Pediatric Endocrinology and Metabolism, Changhua Christian Hospital, Changhua 50050, Taiwan f Department of Pediatrics, Division of Pediatric Neurology and Head, Changhua Christian Hospital, Changhua 50050, Taiwan Received 22 March 1999; received in revised form 17 May 1999; accepted 4 June 1999
To the Editor: Conotruncal and arch artery anomalies have been well known for their frequent association with chromosome 22q11 deletion [1]. We have encountered a newly recognized cardiovascular phenotypes of isolated infundibuloarterial inversion [2] and a fifth aortic arch in an 11-month-old infant who had chromosome 22q11 deletion. An 11-month-old female infant was found to have lip cyanosis, tachycardia, and tachypnea since birth. There was a grade III / VI systolic ejection murmur heard over the bilateral middle sternal border in the 4th intercostal space at birth. A tentative diagnosis of double outlet right ventricle with subaortic ventricular septal defect and pulmonary stenosis was made echocardiographically. She was first admitted due to acute cardiopulmonary distress and seizure at 11 months of age. On physical examination, she was underweight (5.3 kg ,3 percentile), and was looked *Correspondence author. Tel.: 00-886-4-7238595 Ext: 7442; fax: 00886-4-7238847 or 00-886-4-7232942.
acutely ill with acrocyanosis, tachycardia (160 beats / min), and tachypnea (48 breaths / min). The breathing sound was diminished in the left lung field. There was a grade IV/ VI systolic ejection murmur over bilateral middle sternal border. Liver was palpable 5 cm below the right costal margin. Plain chest film and pleural echography suggested massive pleural effusion. Chest tube insertion revealed milky pleural effusion, which is characterized by increased lymphocyte counts (10,514 / mm 3 ) and increased triglyceride level (1,932 mg / dL). The congenital chylothorax was further treated by a pleural-peritoneal shunt, total parenteral nutrition, and then elementary milk supplemented with medium-chain triglycerides. The second and third hospitalizations were related to generalized tonic-clonic seizure and recurrent pneumonia. Calcium levels and immune studies were within normal limits. No evidence of primary immunodeficiency syndrome can be ascribed to. Refractory wheezing, stridor, and fever prompted the fourth hospitalization, during which time bacteremia (Streptococcus viridans) with pneumonia intervened. Wheeze and stridor still lingered despite a complete
0167-5273 / 99 / $ – see front matter 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 99 )00099-6
90
M.-L. Lee et al. / International Journal of Cardiology 71 (1999) 89 – 91
hS,D,Ij, subvalvular and supravalvular pulmonary stenosis, left pulmonary artery stenosis, a right aortic arch, an aberrant left subcalvian artery, and a single coronary artery from the anterior coronary cusp. Electron beam CT or ultrafast CT showed bronchial compression associated with isolated infundibuloarterial inversion and a fifth aortic arch (Fig. 1). At surgery, a complete vascular ring, which was composed of an aberrant left subclavian artery arising from a right arch and giving off a left ligamentum arteriosum to the juxtaductal stenotic left pulmonary artery, was visualized to impinge on the trachea, esophagus, and thoracic duct. A left-sided ligamentum arteriosum was divided to release the tension. A remnant of nonpatent fifth aortic arch, of systemic-tosystemic type, was identified and divided at surgery. The ascending aorta was mobilized and fixed to the sternocostal junction to release tension on the bronchi. She survived a surgical repair of the isolated infundibuloarterial inversion without the use of an extracardiac conduit [3]. The abnormal facies, which bear a resemblance to those of DiGeorge syndrome, and cardiac malformations prompted a chromosome study of 22q11 microdeletion (Fig. 2). She was free of wheezing respiration in a 2-year follow-ups. A lot of cardiovascular malformations, including
Fig. 1. Electron beam CT, right anterior oblique view 158, showed bilateral bronchial stenosis in association with isolated infundibuloarterial inversion and fifth aortic arch. Top: Prior to operation, bilateral bronchi were stenotic and compressed (stars) anteriorly by the right pulmonary artery coursing horizontally. Bottom: The aortic valve of aortic root (arrowhead) was found lying left, posterior, and inferior to the main pulmonary artery (asterisk), which implies presence of inverted normally related great arteries in isolated infundibuloarterial inversion hS,D,Ij. In addition, a remnant of fifth aortic arch (double-headed arrow) was identified.
course of intravenous antibiotics. Echocardiography, cardiac catheterization and angiocardiography showed situs solitus of the viscera and atria, d-loop ventricle, malalignment conoventricular septal defect, ventriculoarterial concordance with levo-posterior aorta, i.e., isolated infundibuloarterial inversion
Fig. 2. Fluorescent in situ hybridization (FISH) study showed chromosome 22q11 microdeletion using Oncor N25 probe. Arrowhead indicates 4 (2 green and 2 red) fluorescein signals in normal chromosome 22. Arrow identifies microdeletion of chromosome 22q11, with only 2 bright green signals.
M.-L. Lee et al. / International Journal of Cardiology 71 (1999) 89 – 91
inflow, outflow, and aortic arch arteries anomalies, can be induced by removal of the cardiac neural crest [4]. Isolated infundibuloarterial inversion (malalignment VSD and infundibular pulmonary stenosis) or inverted tetralogy of Fallot hS,D,Ij [2,3] can be regarded as a phenotype of cardiac outflow tract anomalies, according to the papers described Kirby ML et al. [4]. From the embryologic viewpoint, the role of cardiac neural crest for the conotruncal cardiac anomalies of interrupted aortic arch type B, truncus arteriosus, and tetralogy of Fallot in DiGeorge syndrome [5], velocardiofacial syndrome [6], and conotruncal anomaly face syndrome [7] cannot be overemphasized. From the genetic viewpoint, these conotruncal cardiac anomalies have been well known for their frequent association with chromosome 22q11 deletion in patients with DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome [1,7–9]. It is not far fetched to consider that chromosome 22q11 microdeletion may cause abnormality of the neural crest cells, which renders possible varied cardiac and noncardiac malformations in the above syndromes. There are two types of connection presented as either systemic-to-systemic or systemic-to-pulmonary artery conduits, if the fifth aortic arch persisted [10]. There was one report of tetralogy of Fallot in linkage with persistent fifth aortic arch [11]. Persistent fifth aortic arch can be seen after neural crest ablation in the chick (by letter communication with Kirby ML). It is still unknown that persistent fifth aortic arch, in human being, should be regarded as a member of abnormal patterning of the aortic arch arteries due to abnormality of the neural crest cells. Another interesting report is the finding of chromosome 22q11.2 deletion in a 16-year-old boy with cervical aortic arch, which is believed to arise as a result of a persistent third dorsal arch that reroutes the aortic arch into the cervical region [12]. There was a report of persistent fifth aortic arch in a 2-year-old girl, who presented hypertelorism and small epicanthal fold with hypoplasia of palpebral tissue and flat nasal bridge, and low-set ears with abnormal folds [13]. The facial anomalies in this patient mimicked those described in patients with DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome [7–9]. Patterning of all of the aortic arch vessels is disrupted after neural crest ablation. It seems that the neural crest cells carry instructions for
91
normal patterning for each species. We agree that abnormal patterning of this whole region is possible in the absence of neural crest (by letter communication with Kirby ML). We believe that 22q11 deletion may be associated with defective neural crest development. An experimental model of an animal with altered expression of the 22q11 candidate genes may tell us in the future for sure that this cascade of molecular biology works, i.e., gene 22q11 microdeletion can cause defective or abnormal neural crest cell development and then cardiovascular dysmorphogenesis. To the best of our knowledge, this is the first report of isolated infundibuloarterial inversion and fifth aortic arch associated with 22q11 microdeletion in the English literature.
References [1] Goldmuntz E, Clark BJ, Mitchell LE et al. Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol 1998;32:492–8. [2] Foran RB, Belcourt C, Nanton MA et al. Isolated infundibuloarterial inversion hS,D,Ij: a newly recognized form of congenital heart disease. Am Heart J 1988;116:1337–50. [3] Santini F, Jonas RA, Sanders SP, Van Praagh R. Tetralogy of Fallot hS,D,Ij: successful repair without a conduit. Ann Thorac Surg 1995;59:747–9. [4] Kirby ML, Waldo KL. Role of neural crest in congenital heart disease. Circulation 1990;82:332–40. [5] Van Mierop LHS, Kutsche LM. Cardiovascular anomalies in DiGeorge syndrome and importance of neural crest as a possible pathogenetic factor. Am J Cardiol 1986;58:133–7. [6] McLean SD, Saal HM, Spinner NB, Emanuel BS, Driscoll DA. Velo-cardio-facial syndrome. Am J Dis Child 1993;147:1212–6. [7] Momma K, Kondo C, Matsuoka R. Tetralogy of Fallot with pulmonary atresia associated with chromosome 22q11 deletion. J Am Coll Cardiol 1996;27:198–202. [8] Driscoll DA, Budarf ML, Emanuel BS. A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11. Am J Hum Genet 1992;50:924–33. [9] Goldberg RB, Motzkin B, Marion R, Scambler PJ, Shprintzen RJ. Velo-cardio-facial syndrome: a review of 120 patients. Am J Med Genet 1993;45:313–9. [10] Gerlis LM, Dickinson DF, Wilson N, Gibbs JL. Persistent fifth aortic arch. A report of two new cases and a review of the literature. Int J Cardiol 1987;16:185–92. [11] Donti A, Soavi N, Sabbatani P, Picchio FM. Persistent left fifth aortic arch associated with tetralogy of Fallot. Pediatr Cardiol 1997;18:229–31. [12] Kazuma N, Murakami M, Suzuki Y, Umezu R, Murata M. Cervical aortic arch associated with 22q11.2 deletion. Pediatr Cardiol 1997;18:149–51. [13] Lawrence TYK, Stiles QR. Persistent fifth aortic arch in man. Am J Dis Child 1975;129:1229–31.