eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Cardiology

Heterotaxy, Asplenia

Author: Kevin M Shannon, MD, Associate Professor, Division of Pediatric Cardiology, Director of Pediatric Electrophysiology Program, UCLA School of Medicine; Consulting Staff, Pediatric Cardiology Clinic, Olive View-UCLA Medical Center
Contributor Information and Disclosures

Updated: Apr 23, 2009

Introduction

Background

Asplenia is a heterogeneous disease that primarily affects the asymmetric organs, including the heart, liver, intestines, and spleen. The first published description of asplenia appeared in 1826. Primary manifestations of this disease include cyanotic congenital heart disease and intestinal malrotation.

Transverse ultrasonogram in a patient with asplen...

Transverse ultrasonogram in a patient with asplenia. This image demonstrates the aorta and vena cava on either side of the midline, an appearance that simulates solitus anatomy.

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Transverse ultrasonogram in a patient with asplen...

Transverse ultrasonogram in a patient with asplenia. This image demonstrates the aorta and vena cava on either side of the midline, an appearance that simulates solitus anatomy.


Pathophysiology

The exact cause of asplenia has not been defined but appears to be multifactorial, with some familial predisposition. Embryologically, it results from failure of development of right-left asymmetry.1 All thoracic and abdominal organs can be affected; however, other than the anatomic abnormalities, the function of these organs is affected minimally.2

Cardiac manifestations can range from minor to severe and are related to incomplete or impaired rotation of the heart. Common cardiac findings include persistence of a left-sided superior vena cava (SVC), anomalous pulmonary venous return, common atrium, endocardial cushion defects, and double outlet right ventricle. In addition, bilateral right atrial appendages may be present in at least 20% of patients with asplenia, and their presence is diagnostic of this syndrome. Other thoracic findings include bilateral morphologic right bronchi and trilobed lungs.3

Abdominal findings can include asplenia, transverse liver, and intestinal malrotation.4 Biliary tract abnormalities have also been described but are rarely of clinical significance.

Frequency

United States

Asplenia has a prevalence of less than 0.1% but may account for as much as 1% of the newborn mortality rate. Case reports of familial predisposition are noted, but no clear inheritance pattern or gene has been identified. Anatomic findings have been variable in the families described.

Mortality/Morbidity

Without surgery, the mortality rate of asplenia is 95% in the first year of life. Palliative cardiac surgery improves the survival rate, particularly during infancy, but the 5-year mortality rate remains as high as 50%. Mortality can result from congenital heart disease, intestinal malrotation, or sepsis. In one large retrospective review from Canada, the 1-year mortality rate was 80%.

Race

No predilection based on race has been reported.

Sex

No predilection based on sex has been reported.

Age

Heterotaxy occurs in utero, and the onset of clinical symptoms may be during the neonatal period or later in life, depending on the exact cardiac and visceral lesions.

Clinical

History

Patients with asplenia usually present with symptoms of congenital heart disease in the newborn period. The most common presenting symptom is cyanosis, but murmurs and signs of congestive heart failure can also be presenting signs. A small percentage of patients present with abdominal symptoms or are identified because of an incidental finding of situs abnormalities (eg, dextrocardia, intestinal malrotation). Typically, patients presenting after the newborn period do not have significant congenital heart disease.

Physical

Cyanosis and/or congestive heart failure are the most common physical findings in patients who present in the newborn period. A transverse liver or dextrocardia is often present. Patients who present after the newborn period have predominantly normal physical examination findings, other than a transverse liver and/or dextrocardia. Patients who present with symptoms of malrotation can present with an acute abdomen caused by volvulus.

Causes

The causes of asplenia are unknown, but they appear to be multifactorial and may include inherited predisposition, teratogenic factors, or infection.5,6 No racial, sexual, or socioeconomic predispositions are noted. Although familial cases have been reported, no genes or loci have been identified. Reported patterns of inheritance have been diverse. In several families with multiple affected children, parental consanguinity is present, or rarely an autosomal recessive inheritance pattern is observed. In at least one family, an X-linked inheritance pattern was reported, with the disease present in 11 related males over 2 generations. Different forms of heterotaxy, including asplenia and polysplenia, may occur within the same family.

The molecular basis for heterotaxy may relate to defects in genes responsible for laterality, such as the growth factor genes: nodal, activin, and lefty.

More on Heterotaxy, Asplenia

Overview: Heterotaxy, Asplenia
Differential Diagnoses & Workup: Heterotaxy, Asplenia
Treatment & Medication: Heterotaxy, Asplenia
Follow-up: Heterotaxy, Asplenia
Multimedia: Heterotaxy, Asplenia
References
Further Reading
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References

  1. Jacobs JP, O'Brien SM, Chai PJ, Morell VO, Lindberg HL, Quintessenza JA. Management of 239 patients with hypoplastic left heart syndrome and related malformations from 1993 to 2007. Ann Thorac Surg. May 2008;85(5):1691-6; discussion 1697. [Medline].

  2. Konstantinidou A, Sifakis S, Koukoura O, Mantas N, Agrogiannis G, Patsouris E. Pancreatic aplasia in a fetus with asplenia-cardiovascular defect-heterotaxy (Ivemark syndrome). Birth Defects Res A Clin Mol Teratol. Aug 2008;82(8):601-4. [Medline].

  3. Ming Z, Hong S, Biao J. Images in cardiovascular medicine. Asplenia syndrome with bilateral tracheal bronchi. Circulation. Jul 8 2008;118(2):196-7. [Medline].

  4. Ferdman B, States L, Gaynor JW, Hedrick HL, Rychik J. Abnormalities of intestinal rotation in patients with congenital heart disease and the heterotaxy syndrome. Congenit Heart Dis. Jan 2007;2(1):12-8. [Medline].

  5. Jan IS, Tsai TH, Chen JM, et al. Hypoglycemia associated with bacteremic pneumococcal infections. Int J Infect Dis. Dec 12 2008;[Medline].

  6. Bertran SK, Donoso FA, Cruces RP, Diaz RF, Arriagada SD. [Congenital asplenia and pneumococcal purpura fulminans in a pediatric patient: case report with pathological findings and review]. Rev Chilena Infectol. Feb 2009;26(1):55-9. [Medline].

  7. Atkinson DE, Drant S. Diagnosis of heterotaxy syndrome by fetal echocardiography. Am J Cardiol. Nov 1 1998;82(9):1147-9, A10. [Medline].

  8. Bartram U, Wirbelauer J, Speer CP. Heterotaxy syndrome -- asplenia and polysplenia as indicators of visceral malposition and complex congenital heart disease. Biol Neonate. 2005;88(4):278-90. [Medline].

  9. Chen SJ, Li YW, Wang JK, et al. Usefulness of electron beam computed tomography in children with heterotaxy syndrome. Am J Cardiol. Jan 15 1998;81(2):188-94. [Medline].

  10. Ditchfield MR, Hutson JM. Intestinal rotational abnormalities in polysplenia and asplenia syndromes. Pediatr Radiol. May 1998;28(5):303-6. [Medline].

  11. Eronen M, Kajantie E, Boldt T. Right atrial isomerism in four siblings. Pediatr Cardiol. 2004;24:141-4. [Medline]. [Full Text].

  12. Freedom RM, Jaeggi ET, Lim JS, Anderson RH. Hearts with isomerism of the right atrial appendages - one of the worst forms of disease in 2005. Cardiol Young. 2005;15:554-67. [Medline]. [Full Text].

  13. Hashmi A, Abu-Sulaiman R, McCrindle BW, et al. Management and outcomes of right atrial isomerism: a 26-year experience. J Am Coll Cardiol. Apr 1998;31(5):1120-6. [Medline].

  14. Hofstaetter C, Plath H, Hansmann M. Prenatal diagnosis of abnormalities of the fetal venous system. Ultrasound Obstet Gynecol. Mar 2000;15(3):231-41. [Medline].

  15. Kawahira Y, Kishimoto H, Kawata H, et al. Morphologic analysis of common atrioventricular valves in patients with right atrial isomerism. Pediatr Cardiol. Mar-Apr 1997;18(2):107-11. [Medline].

  16. Levine JC, Walsh EP, Saul JP. Radiofrequency ablation of accessory pathways associated with congenital heart disease including heterotaxy syndrome. Am J Cardiol. 1993;72:689-93. [Medline].

  17. Mahle WT, Silverman NH, Marx GR, Anderson RH. Echo-morphological correlates concerning the functionally univentricular heart in the setting of isomeric atrial appendages. Cardiol Young. 2006;16 Suppl 1:35-42. [Medline]. [Full Text].

  18. Ruscazio M, Van Praagh S, Marrass AR, et al. Interrupted inferior vena cava in asplenia syndrome and a review of the hereditary patterns of visceral situs abnormalities. Am J Cardiol. Jan 1 1998;81(1):111-6. [Medline].

  19. Ticho BS, Van Praagh R. Inherited structural heart diseases associated with arrhythmias: Defects in laterality. In: Berul CI, Towbin JA, eds. Molecular Genetics of Cardiac Electrophysiology. Boston, Mass:. Kluwer Academic Publishers;2000:317-328.

  20. Uemura H, Ho SY, Anderson RH, Yagihara T. Ventricular morphology and coronary arterial anatomy in hearts with isometric atrial appendages. Ann Thorac Surg. May 1999;67(5):1403-11. [Medline].

  21. Uemura H, Ho SY, Devine WA, Anderson RH. Analysis of visceral heterotaxy according to splenic status, appendage morphology, or both. Am J Cardiol. Oct 15 1995;76(11):846-9. [Medline].

  22. Wu MH, Wang JK, Lin JL, et al. Supraventricular tachycardia in patients with right atrial isomerism. J Am Coll Cardiol. Sep 1998;32(3):773-9. [Medline].

  23. Yoo SJ, Kim YM, Choe YH. Magnetic resonance imaging of complex congenital heart disease. Int J Card Imaging. Apr 1999;15(2):151-60. [Medline].

  24. Zissin R, Rathaus V, Oscadchy A, et al. Intestinal malrotation as an incidental finding on CT in adults. Abdom Imaging. Nov-Dec 1999;24(6):550-5. [Medline].

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Keywords

asplenia, right atrial isomerism, laterality defects, cyanotic congenital heart disease, intestinal malrotation, anomalous pulmonary venous return, common atrium, endocardial cushion defects, double outlet right ventricle, treatment, diagnosis, biliary tract abnormalities, transverse liver, congestive heart failure, volvulus

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Contributor Information and Disclosures

Author

Kevin M Shannon, MD, Associate Professor, Division of Pediatric Cardiology, Director of Pediatric Electrophysiology Program, UCLA School of Medicine; Consulting Staff, Pediatric Cardiology Clinic, Olive View-UCLA Medical Center
Kevin M Shannon, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Medical Editor

Charles I Berul, MD, Associate Professor of Pediatrics, Harvard Medical School; Senior Associate, Department of Cardiology, Children's Hospital of Boston
Charles I Berul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, Heart Rhythm Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Julian M Stewart, MD, PhD, Associate Chairman of Pediatrics, Director, Center for Hypotension, Westchester Medical Center; Professor of Pediatrics and Physiology, New York Medical College
Julian M Stewart, MD, PhD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

CME Editor

Gilbert Z Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College; Consulting Staff, Department of Pediatrics, Sound Shore Medical Center
Gilbert Z Herzberg, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Chief Editor

Stuart Berger, MD, Professor of Pediatrics, Division of Cardiology, Medical College of Wisconsin; Chief of Pediatric Cardiology, Medical Director of Pediatric Heart Transplant Program, Medical Director of The Heart Center, Children's Hospital of Wisconsin
Stuart Berger, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American College of Chest Physicians, American Heart Association, and Society for Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

 
 
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