American Journal of Medical Genetics 1:319-321 (1978)
Autosomal Dominant Inheritance of Annular Pancreas Laird G. Jackson and Panayotos Apostolides Departments of Medicine, Obstetrics and Gynecology, and Pediatrics, Thomas Jefferson University, Philadelphia
This report describes a family with apparent autosomal dominant transmission of congenital annular pancreas. Four individuals in two generations were affected; all developed duodenal obstruction. The implications for genetic counseling are discussed. Key words: annular pancreas, autosomal dominant inheritance, genetic counseling
INTRODUCTION
Annular pancreas is a relatively common congenital anomaly producing varying degrees of high intestinal obstruction amenable to surgical correction [ 1-31 . To our knowledge it has not been reported in a familial pattern consistent with transmission of a single gene [4] . This article describes such a family, suggesting that certain cases of annular pancreas are due to an autosomal domimnt gene. Within such a family genetic counseling might alert the relatives and their physicians to prompt neonatal diagnosis and surgical correction before serious symptoms or complications have occurred. CASE REPORTS
The proband (IV-1, Fig. 1) was born on April 27, 1967, after an uneventful course of pregnancy and labor. The girl weighed 2,440 gm at birth and was well for the first 2 4 hours of life. Then, the infant began to spit up her feedings and to show clinical signs of intestinal obstruction. Radiographs showed a high intestinal obstruction with a double air-fluid level in the upper portion of the intestinal tract, and exploratory abdominal surgery was performed. An annular pancreas was found to have produced a duodenal stenosis. The anomaly was corrected by duodenojejunostomy and the child r e c o w e d uneventfully; she has been asymptomatic since that time. After the birth of the first child, a review of the mother’s (111-4; Fig. 1) history showed that she also had had gastrointestinal difficulties as a child. Symptoms of upper gastrointestinal obstruction appeared a few weeks after her birth on March 28, 1942. Nausea and protracted vomiting were the chief symptoms. Radiographs showed evidence Received for publication August 15,1977; accepted October 14, 1977. Address reprint requests to Laird G. Jackson, MD, Division of Medical Genetics, Thomas Jefferson University, 1025 Walnut Street, Philadelphia, PA 19107.
0148-7299/78/0103-0319$01.100 1978 Alan R. Liss, Inc
320
Jackson and Apostolides
of pylorospasm, and abdominal exploration and a Ramstedt pyloroplasty were performed. Following the procedure, the nausea and vomiting returned and persisted intermittently over the next three years. On February 7 , 1946, she had a repeat surgical exploration of the abdomen because of persistence of the symptoms. At the operation, an annular lesion stenosing the duodenum was noted in the area of the ampulla of Vater; it was relieved by a gastrojejunostomy. The diagnosis was reported to the family as an annular pancreas with duodenal stenosis, but written operative and pathological records were subsequently lost. Radiographic examination for minor upper gastrointestinal symptoms in 1967 showed the gastrojejunostomy to be in good functional condition. She has remained asymptomatic since that time. This mother's second child (IV-2, Fig. 1) was born on July 3, 1968, after another uneventful pregnancy and labor. He weighed 3,010 gm at birth and was, because of the family history, promptly examined with upper gastrointestinal radiography. A high gastrointestinal obstruction was seen and the abdomen was therefore surgically explored. Again, an annular pancreas associated with duodenal stenosis was seen and repaired by creation of a duodenojejunostomy. The infant recovered uneventfully and has been asymptomatic since then. The third child, a boy (IV-3, Fig. l ) , was born on June 5, 1972, without incident. E a ~ l yupper gastrointestinal radiographs were normal and the infant had no gastrointestinal symptoms. The fourth child, a girl (IV-4, Fig. l), was born on April 23, 1975, and weighed 3,540 gm.Again, early radiographc studies showed a high intestinal obstruction. The infant's abdomen was explored surgically when she was 24 hours old and an annular pancreas with duodenal stenosis was repaired by creation of a duodenojejunostomy. This child also has been well since surgery. Karyotypes of the parents (111-1,4, Fig. l), and the first two children (IV-1,2; Fig. I), were normal. Blood group studies of the same four individuals showed no instance of unusual gene transmission. Aside from the four affected persons described above, all relatives in the pedigree (Fig. 1) were free of gastrointestinal disease. The mother's parents (11-5, Fig. 1) are of Jewish background and were 28 and 26 years old at her birth. DISCUSSION
Annular pancreas is a congenital malformation that is usually symptomless unless it is associated with duodenal stenosis or atresia, or unless other supervening disease causes obstruction or pancreatitis [3,5]. In most cases the lesion is probably caused by incomplete rotation of the pancreatic anlage so that portions of the pancreas remain on both
I
Fig. 1. Pedigree of the family studied.
D o m i n a n t Annular Pancreas
32 1
sides of the duodenum. It is estimated to occur once in 10,000live births [6]. About 20% of cases occur in association with Down syndrome [7] . Isolated duodenal atresia has been reported in six twin sets and in four siblings in a single family [ l ] ,but annular pancreas by itself or in association with duodenal atresia or stenosis has not been described in a mendelian pattern [ l , 41 , with the possible exception of a single report of sibling occurrence [8] . The present family appears to be the first reported instance of autosomal dominant transmission of annular pancreas. The lack of other reports of mendelian transmission of this anomaly suggests either that an autosomal dominant gene is indeed a rare cause of annular pancreas and that the family discussed in this paper represents an unusual exception, or that many instances of dominant annular pancreas go unnoticed because they are silent and not detected except at autopsy; the familial occurrence can then easily be overlooked. The present family’s experience shows that the possibility of autosomal dominant transmission of annular pancreas with duodenal obstruction should be kept in mind for genetic counseling. Early observation and diagnosis make the defect accessible to corrective surgery. This might be anticipated in high-risk cases that are identified on the basis of the family history. REFERENCES 1. Fonkalsrud EW, deLorimer PA, Huys DM: Congenital atresia and stenosis of the duodenum. Pediatrics 43:79-83, 1969. 2. Fonkalstud EW: Duodenal atresia and stenosis. In Bergsma D (ed): “Birth Defects Atlas and Compendium.” Baltimore: Williams & Wilkins, 1973, p 353. 3. Rickham PP: Duodenal atresia and stenosis; annular pancreas. In Rickham PP, Johnston JH, (eds): “Neonatal Surgery.” New York: Appleton-Century-Crofts, 1969, pp 286-302. 4. McKusick VA: “Mendelkan Inheritance in Man.” Baltimore: Johns Hopkins University Press, 1975, p 407. 5. Warkany .I: “Congenital Malformations.” Chicago: Year Book Medical Publishers 197 1, pp 730-731. 6. Pickett LK: Annular pancreas. In Bergsma D (ed): “Birth Defects Atlas and Compendium.” Baltimore: Williams & Wilkins, 1973, p 171. 7. deWolff E: Etude clinique de 134 mongoliens. Ann Paediatr 202:suppl, 1964. 8. Montgomery RC, Poindexter MH, Hall GH, Leigh JE: Report of a case of annular pancreas of the newborn in two consecutive siblings. Pediatrics 48:148-149, 1971.
Edited by J. H e r r m a n n
Autosomal Dominant Inheritance of Annular Pancreas Laird G. Jackson and Panayotos Apostolides Departments of Medicine, Obstetrics and Gynecology, and Pediatrics, Thomas Jefferson University, Philadelphia
This report describes a family with apparent autosomal dominant transmission of congenital annular pancreas. Four individuals in two generations were affected; all developed duodenal obstruction. The implications for genetic counseling are discussed. Key words: annular pancreas, autosomal dominant inheritance, genetic counseling
INTRODUCTION
Annular pancreas is a relatively common congenital anomaly producing varying degrees of high intestinal obstruction amenable to surgical correction [ 1-31 . To our knowledge it has not been reported in a familial pattern consistent with transmission of a single gene [4] . This article describes such a family, suggesting that certain cases of annular pancreas are due to an autosomal domimnt gene. Within such a family genetic counseling might alert the relatives and their physicians to prompt neonatal diagnosis and surgical correction before serious symptoms or complications have occurred. CASE REPORTS
The proband (IV-1, Fig. 1) was born on April 27, 1967, after an uneventful course of pregnancy and labor. The girl weighed 2,440 gm at birth and was well for the first 2 4 hours of life. Then, the infant began to spit up her feedings and to show clinical signs of intestinal obstruction. Radiographs showed a high intestinal obstruction with a double air-fluid level in the upper portion of the intestinal tract, and exploratory abdominal surgery was performed. An annular pancreas was found to have produced a duodenal stenosis. The anomaly was corrected by duodenojejunostomy and the child r e c o w e d uneventfully; she has been asymptomatic since that time. After the birth of the first child, a review of the mother’s (111-4; Fig. 1) history showed that she also had had gastrointestinal difficulties as a child. Symptoms of upper gastrointestinal obstruction appeared a few weeks after her birth on March 28, 1942. Nausea and protracted vomiting were the chief symptoms. Radiographs showed evidence Received for publication August 15,1977; accepted October 14, 1977. Address reprint requests to Laird G. Jackson, MD, Division of Medical Genetics, Thomas Jefferson University, 1025 Walnut Street, Philadelphia, PA 19107.
0148-7299/78/0103-0319$01.100 1978 Alan R. Liss, Inc
320
Jackson and Apostolides
of pylorospasm, and abdominal exploration and a Ramstedt pyloroplasty were performed. Following the procedure, the nausea and vomiting returned and persisted intermittently over the next three years. On February 7 , 1946, she had a repeat surgical exploration of the abdomen because of persistence of the symptoms. At the operation, an annular lesion stenosing the duodenum was noted in the area of the ampulla of Vater; it was relieved by a gastrojejunostomy. The diagnosis was reported to the family as an annular pancreas with duodenal stenosis, but written operative and pathological records were subsequently lost. Radiographic examination for minor upper gastrointestinal symptoms in 1967 showed the gastrojejunostomy to be in good functional condition. She has remained asymptomatic since that time. This mother's second child (IV-2, Fig. 1) was born on July 3, 1968, after another uneventful pregnancy and labor. He weighed 3,010 gm at birth and was, because of the family history, promptly examined with upper gastrointestinal radiography. A high gastrointestinal obstruction was seen and the abdomen was therefore surgically explored. Again, an annular pancreas associated with duodenal stenosis was seen and repaired by creation of a duodenojejunostomy. The infant recovered uneventfully and has been asymptomatic since then. The third child, a boy (IV-3, Fig. l ) , was born on June 5, 1972, without incident. E a ~ l yupper gastrointestinal radiographs were normal and the infant had no gastrointestinal symptoms. The fourth child, a girl (IV-4, Fig. l), was born on April 23, 1975, and weighed 3,540 gm.Again, early radiographc studies showed a high intestinal obstruction. The infant's abdomen was explored surgically when she was 24 hours old and an annular pancreas with duodenal stenosis was repaired by creation of a duodenojejunostomy. This child also has been well since surgery. Karyotypes of the parents (111-1,4, Fig. l), and the first two children (IV-1,2; Fig. I), were normal. Blood group studies of the same four individuals showed no instance of unusual gene transmission. Aside from the four affected persons described above, all relatives in the pedigree (Fig. 1) were free of gastrointestinal disease. The mother's parents (11-5, Fig. 1) are of Jewish background and were 28 and 26 years old at her birth. DISCUSSION
Annular pancreas is a congenital malformation that is usually symptomless unless it is associated with duodenal stenosis or atresia, or unless other supervening disease causes obstruction or pancreatitis [3,5]. In most cases the lesion is probably caused by incomplete rotation of the pancreatic anlage so that portions of the pancreas remain on both
I
Fig. 1. Pedigree of the family studied.
D o m i n a n t Annular Pancreas
32 1
sides of the duodenum. It is estimated to occur once in 10,000live births [6]. About 20% of cases occur in association with Down syndrome [7] . Isolated duodenal atresia has been reported in six twin sets and in four siblings in a single family [ l ] ,but annular pancreas by itself or in association with duodenal atresia or stenosis has not been described in a mendelian pattern [ l , 41 , with the possible exception of a single report of sibling occurrence [8] . The present family appears to be the first reported instance of autosomal dominant transmission of annular pancreas. The lack of other reports of mendelian transmission of this anomaly suggests either that an autosomal dominant gene is indeed a rare cause of annular pancreas and that the family discussed in this paper represents an unusual exception, or that many instances of dominant annular pancreas go unnoticed because they are silent and not detected except at autopsy; the familial occurrence can then easily be overlooked. The present family’s experience shows that the possibility of autosomal dominant transmission of annular pancreas with duodenal obstruction should be kept in mind for genetic counseling. Early observation and diagnosis make the defect accessible to corrective surgery. This might be anticipated in high-risk cases that are identified on the basis of the family history. REFERENCES 1. Fonkalsrud EW, deLorimer PA, Huys DM: Congenital atresia and stenosis of the duodenum. Pediatrics 43:79-83, 1969. 2. Fonkalstud EW: Duodenal atresia and stenosis. In Bergsma D (ed): “Birth Defects Atlas and Compendium.” Baltimore: Williams & Wilkins, 1973, p 353. 3. Rickham PP: Duodenal atresia and stenosis; annular pancreas. In Rickham PP, Johnston JH, (eds): “Neonatal Surgery.” New York: Appleton-Century-Crofts, 1969, pp 286-302. 4. McKusick VA: “Mendelkan Inheritance in Man.” Baltimore: Johns Hopkins University Press, 1975, p 407. 5. Warkany .I: “Congenital Malformations.” Chicago: Year Book Medical Publishers 197 1, pp 730-731. 6. Pickett LK: Annular pancreas. In Bergsma D (ed): “Birth Defects Atlas and Compendium.” Baltimore: Williams & Wilkins, 1973, p 171. 7. deWolff E: Etude clinique de 134 mongoliens. Ann Paediatr 202:suppl, 1964. 8. Montgomery RC, Poindexter MH, Hall GH, Leigh JE: Report of a case of annular pancreas of the newborn in two consecutive siblings. Pediatrics 48:148-149, 1971.
Edited by J. H e r r m a n n
