Article in PDF format - JOP Home page
JOP. J Pancreas (Online) 2007; 8(4):433-437.
Dorsal Pancreas Agenesis and Polysplenia/Heterotaxy Syndrome: A Novel Association with Aortic Coarctation and a Review of the Literature
Suraj Kapa1, Ferga C Gleeson2, Santhi Swaroop Vege2
Divisions of 1Internal Medicine and 2Gastroenterology and Hepatology, Mayo Clinic College of Medicine. Rochester, MN, USA
Context Agenesis of the dorsal pancreas is very rare and may be associated with other congenital disease states. It has a rare association with polysplenia/heterotaxy syndrome. Most commonly, these states occur due to errors in development of the asymmetric organs and may be associated with benign to severe congenital cardiac malformations.
Case report We report a case of a 25-year-old male with known coarctation of the aorta who was otherwise asymptomatic. Following a routine cardiac examination, he was incidentally discovered to have an absent body and tail of the pancreas on imaging. Further testing demonstrated findings consistent with a diagnosis of polysplenia/heterotaxy syndrome with agenesis of the dorsal pancreas.
Conclusions In patients with congenital heart disease, there is increased likelihood for the presence of other congenital malformations. In particular, polysplenia/heterotaxy syndrome, while very rare, has been shown to be associated with cardiac abnormalities. The importance in diagnosis lies in the potential clinical consequences of polysplenia/heterotaxy syndrome and agenesis of the dorsal pancreas, including late-onset diabetes mellitus, pancreatitis, and intestinal volvulus.
Polysplenia/heterotaxy syndrome is a relatively rare disorder often involving multiple cardiac and gastrointestinal structural abnormalities with possible effects on normal physiology. Patients with polysplenia often present with atrioventricular septal defects and may have anomalous inferior vena caval flow or other gastrointestinal structural abnormalities including partial or complete agenesis of the dorsal pancreas. These findings may have clinical relevance with a possible increased risk for intestinal volvulus, diabetes mellitus or pancreatitis.
We report a unique case of agenesis of the dorsal pancreas in association with polysplenia/heterotaxy syndrome incidentally identified in an otherwise asymptomatic patient with a prior diagnosis of aortic coarctation.
A 25-year-old asymptomatic male with a surgically repaired coarctation of the aorta and hemodynamically insignificant pulmonary stenosis presented to the pancreas clinic via the adult congenital heart disease clinic following an incidental thoracic CT finding of polysplenia with multiple accessory splenules in conjunction with the absence of identifiable pancreatic tissue. His medical history was unremarkable for polyuria, polydipsia, weight loss, steatorrhea, or pancreatitis. Physical exam demonstrated a non-tender, non-distended abdomen without notable hepatomegaly, splenomegaly, palpable masses, or audible bruits. Laboratory values revealed normal pancreatic and liver biochemistry, fasting glucose and lipid profile.
A pancreas protocol CT scan verified complete agenesis of the dorsal pancreas in addition to findings of polysplenia and prominence of the azygous vein with absence of the suprarenal inferior vena cava (Figures 1 and 2). The pancreatic head was prominent in size representing some mild compensatory hypertrophy. In the absence of clinical endocrine or exocrine pancreatic dysfunction no further invasive studies were performed.
The incidental findings in our patient are consistent with that of polysplenia/heterotaxy syndrome, which belongs to a spectrum of cardiosplenic syndromes. Studies suggest that up to 2.2% of patients with congenital heart defects may have an underlying splenic abnormality . There is a further significant association between developmental splenic abnormalities and malformation of the gastroenterologic system, including, but not limited to, the abdominal vasculature, in particular the inferior vena cava, pancreas, small intestine, and liver .
Symmetry is a characteristic of the mammalian phenotype, although much of the internal anatomy is asymmetric. This is particularly true in the cardiovascular, pulmonary, and gastrointestinal systems. These organs form and evolve around the embryonic midline. The normal arrangement of the asymmetric organs is called situs solitus. In extreme cases, all of the midline structures may be rotated around the midline, resulting in a mirror image of the normal anatomy, termed situs inversus. Intermediate states of malrotation are termed situs ambiguus.
Grouping of patients with situs ambiguus is based on whether the right or the left sided structures predominate . Patients with left-sided symmetry are characterized as having polysplenia, which includes either a segmented spleen or multiple splenules that may or may not be functional. Asplenia is associated with right-sided symmetry. More recently, this spectrum of abnormalities has been termed polysplenia syndrome to denote the continuum of possible midline derangements seen in this population.
Abnormalities in this population result from an inability during embryogenesis to fully define laterality, thus resulting in maldevelopment of the asymmetric organs, sparing the symmetric structures. This inability to define laterality is most often sporadic but has been suggested to have possible autosomal and X-linked inheritance patterns. Mouse models have suggested a number of possibly involved genetic mutations, including that of the transforming growth factor beta pathway, though relationship to humans remains to be defined . Unfortunately, the ultimate disposition of organs in this syndrome is largely random, and the defined right or left sided tendency is just that - a tendency - explaining the terming of polysplenia syndrome.
Most commonly, patients present due to symptomatic cardiac abnormalities at birth, as in the case of our patient. However, in some cases, patients may present later in life [5, 6]. The most common anatomic anomaly that points towards a diagnosis of polysplenia syndrome is inferior vena cava interruption with azygous or hemiazygous continuation, though this finding is not necessarily specific for polysplenia . One study suggested that this anatomic finding, in combination with cardiac or situs abnormalities, should suggest a specific diagnosis of a cardiosplenic syndrome, in particular polysplenia .
Cardiac anomalies in these patients may include atrioventricular valvular abnormalities, total anomalous pulmonary venous connection, rotation of the heart about its axis, presence of a single atria, or aortic outflow obstruction at the level of the subaortic outflow tract or at the level of the valve . Patients with polysplenia will often have no notable cardiac defect. If there is an abnormality present, it is most commonly an atrioventricular septal defect. One case series involving thirteen patients suggested that the most common findings are atrioventricular channel and great vessel anomalies . In our patient, there was never an atrioventricular septal defect noted but rather aortic coarctation and pulmonary stenosis, though the latter was not considered to be hemodynamically significant. Coarctation of the aorta is not an uncommon finding and often will not present until older age. Due to this, other congenital malformations that may coexist with coarctation may go undiagnosed even after finding a coarctation, as in our patient. The spectrum of findings involving the diagnosis of polysplenia/heterotaxy syndrome in association with an isolated coarctation of the aorta has never been reported to our knowledge in the English literature.
Gastrointestinal abnormalities may include a midline liver and gallbladder, right-sided stomach and spleen, small bowel and colon rotational abnormalities, truncation of the pancreas, extrahepatic biliary malformations and ipsilateral location of the aorta and inferior vena cava . If the child survives the potential cardiovascular effects of the syndrome, gastrointestinal abnormalities have the potential to cause significant problems, including bile flow abnormalities, intestinal volvulus later in life, and diabetes mellitus or pancreatitis related to maldevelopment. In neonates, there is a significant association between biliary atresia and polysplenia, with a further association with anomalous portal venous connections that may be clinically relevant in the context of planned surgical intervention .
Agenesis of the dorsal pancreas has been previously described in polysplenia . The clinical significance of this finding relates to a possible relationship to early or late onset diabetes mellitus [14, 15] or the increased incidence of pancreatitis [16, 17]. Computed tomography scanning and ERCP are useful in identifying this finding , although the findings must be distinguished between distal pancreas fat replacement and agenesis . On imaging, fat replacement will be distinguished by abundant fat tissue seen anterior to the splenic vein, whereas agenesis of the dorsal pancreas will be characterized by filling of the distal pancreatic bed with stomach and intestines, as in the case of our patient. However, in order to differentiate complete versus partial agenesis of the dorsal pancreas, ERCP is necessary in order to define absence of the dorsal ductal system, the accessory duct, and the minor papilla . Complete agenesis is actually quite rare, with a total of fifteen cases being reported between 1913 and 2005 [21, 22, 23]. The increased likelihood of pancreatitis in this patient population with dorsal agenesis has been proposed to be due to either sphincter of Oddi dysfunction  or higher intrapancreatic duct pressures due to hypertrophy of the ventral gland . Diagnosis may be achieved by a combination of computed tomography or MRI scanning and ERCP. Endoscopic ultrasound has also been proposed as an alternative diagnostic modality .
To conclude, the association between dorsal pancreas agenesis, features of polysplenia/heterotaxy syndrome, and coarctation of the aorta is an interesting collection of findings that has potential clinical correlation related to a possible but as of yet not completely clear propensity for the development of diabetes mellitus or pancreatitis later in life.
Combs LS, Gupta S, Mehta A. Evaluation of spleen in children with heterotaxia and congenital heart disease. Tenn Med 2004; 97:161-3. [More details]
Bartram U, Wirbelauer J, Speer CP. Heterotaxy syndrome - asplenia and polysplenia as indicators of visceral malposition and complex congenital heart disease. Biol Neonate 2005; 88:278-90. [More details]
Winer-Muram HT. Adult presentation of heterotaxic syndromes and related complexes. J Thorac Imaging 1995; 10:43-57. [More details]
Ticho BS, Goldstein AM, Van Praagh R. Extracardiac anomalies in the heterotaxy syndromes with focus on anomalies of midline-associated structures. Am J Cardiol 2000; 85:729-34. [More details]
Bobba RK, Arsura EL, Naseem M, Ashraf N. Polysplenia in an elderly male: diagnostic approaches and review of the literature. Eur J Intern Med 2005; 16:608-9. [More details]
Naranjo Gomez A, Rodriguez Sanjuan JC, Casado Martin F, Del Castillo Diego J, Pagola Serrano MA. Polysplenia with partial abdominal visceral heterotaxia and small pancreas. Rev Esp Enferm Dig 1994; 85:395-7. [More details]
Applegate KE, Goske MJ, Pierce G, Murphy D. Situs revisited: imaging of the heterotaxy syndrome. Radiographics 1999; 19:837-52. [More details]
Sheley RC, Nyberg DA, Kapur R. Azygous continuation of the interrupted inferior vena cava: a clue to prenatal diagnosis of the cardiosplenic syndromes. J Ultrasound Med 1995; 14:381-7. [More details]
Van Praagh S, Geva T, Friedberg DZ, Oechler H, Colli A, Frigiola A, Van Praagh R. Aortic outflow obstruction in visceral heterotaxy: a study based on twenty postmortem cases. Am Heart J 1997; 133:558-69. [More details]
Marton T, Cesko I, Hajdu J, Hargitai B, Papp Z. Heterotaxy syndrome, analysis of 13 cases and review of the literature. Orv Hetil 2002; 142:299-301. [More details]
Fulcher AS, Turner MA. Abdominal manifestations of situs anomalies in adults. Radiographics 2002; 22:1439-56. [More details]
Andreani P, Srinivasan P, Ball CS, Heaton ND, Rela M. Congenital absence of the portal vein in liver transplantation for biliary atresia. Int J Surg Investig 2000; 2:81-4. [More details]
Maier M, Wiesner W, Mengiardi B. Annular pancreas and agenesis of the dorsal pancreas in a patient with polysplenia syndrome. AJR Am J Roentgenol 2007; 188:W150-3. [More details]
Ashraf A, Abdullatif H, Hardin W, Moates JM. Unusual case of neonatal diabetes mellitus due to congenital pancreas agenesis. Pediatr Diabetes 2005; 6:239-43. [More details]
Wildling R, Schnedl WJ, Reisinger EC, Schreiber F, Lipp RW, Lederer A, Krejs GJ. Agenesis of the dorsal pancreas in a woman with diabetes mellitus and in both of her sons. Gastroenterology 1993; 104:1182-6. [More details]
Rakesh K, Choung OW, Reddy ON. Agenesis of the dorsal pancreas (ADP) and pancreatitis - is there an association? Indian J Gastroenterol 2006; 25:35-6. [More details]
Oldenburg B, van Leeuwen MS, van Berge Henegouwen GP, Koningsberger JC. Pancreatitis and agenesis of the dorsal pancreas. Eur J Gastroenterol Hepatol 1998; 10:887-9. [More details]
Lingareddy S, Duvvuru NR, Guduru VR, Lakhtakia S, Kalapala R. Dorsal agenesis of pancreas: CT and ERCP. Gastrointest Endosc 2007; 65:157-8. [More details]
Karcaaltincaba M. CT differentiation of distal pancreas fat replacement and distal pancreas agenesis. Surg Radiol Anat 2006; 28:637-41. [More details]
Schnedl WJ, Reisinger EC, Schreiber F, Pieber TR, Lipp RW, Krejs GJ. Complete and partial agenesis of the dorsal pancreas within one family. Gastrointest Endosc 1995; 42:485-7. [More details]
Guclu M, Serin E, Ulucan S, Kul K, Ozer B, Gumurdulu Y, et al. Agenesis of the dorsal pancreas in a patient with recurrent acute pancreatitis: case report and review. Gastrointest Endosc 2004; 60:472-5. [More details]
Fukuoka K, Ajiki T, Yamamoto M, Fujiwara H, Onoyama H, Fujita T, et al. Complete agenesis of the dorsal pancreas. J Hepatobiliary Pancreat Surg 1999; 6:94-7. [More details]
Balakrishnan V, Narayanan VA, Siyad I, Radhakrishnan L, Nair P. Agenesis of the dorsal pancreas with chronic calcific pancreatitis. case report, review of the literature and genetic basis. JOP. J Pancreas (Online) 2006; 7:651-9. [More details]
Nishimori I, Okazaki K, Morita M, Miyao M, Sakamoto Y, Kagiyama S, et al. Congenital hypoplasia of the dorsal pancreas: with special reference to duodenal papillary dysfunction. Am J Gastroenetrol 1990; 85:1029-33. [More details]
Gold RP. Agenesis and pseudo-agenesis of the dorsal pancreas. Abdom Imaging 1993; 18:141-4. [More details]
Sempere L, Aparicio JR, Martinez J, Casellas JA, de Madaria E, Perez-Mateo M. Role of endoscopic ultrasound in the diagnosis of agenesis of the dorsal pancreas. JOP. J Pancreas (Online) 2006; 7:411-6. [More details]
Article in PDF format
Received March 21st, 2007- Accepted April 16th, 2007
Keywords Aortic Coarctation; Embryonic Development; Heart Defects, Congenital; Pancreas
Conflict of interest The authors have no potential conflicts of interest
Santhi Swaroop Vege
Mayo Clinic College of Medicine
200 First Street SW
Rochester, MN 55905