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Gastroschisis: No myth
Gastroschisis: No Myth B y J . A. N o o r d i j k and F. B l o e m s m a - J o n k m a n 9 The question has been raised whether o m p h a l o c e l e and gastroschisis are f u n d a m e n t a l l y different pathologic entities, or whether they are only
different manifestations of the same underlying cause. After studying the family history of 37 patients
with omphalocele end 14 patients with gastroschisis, it seems probable that hereditary factors contribute to the origin of o m p h a l o c e l e s . Such f a c t o r s were not shown in patients with gastroschisis. Therefore genetic evaluation and counselling is advocated for the parents of a child with o m p h a l o c e l e . IN DEX W O R D S : O m p h a l o c e l e ; gastroschisis.
N A R E C E N T A R T I C L E , Shaw I qualified as a " m y t h " the distinction made between gastroschisis and omphalocele. He states that, from a developmental standpoint, categoric separation of these pathologic entities is untenable, even if it has been clinically useful. There is still some confusion about the terminology, and often the concepts of gastroschisis and omphalocele are used indiscriminately, although there are important differences.
I
Omphalocele There is always a sac present, which has or has not been ruptured during birth, and often contains parts of liver, stomach, or spleen (Fig. 1). The umbilical cord always emerges from the top of this sac. The abdominal defect is usually large. M o r e o v e r o m p h a l o c e l e s are o f t e n combined with other serious congenital abnormalities, of which Cardiac anomalies have the greatest influence upon the chance of survival.
Gastroschisis There is never a sac present, and the umbilical cord emerges at its normal site on the abdominal wall, usually to the left of the defect that on the average is much smaller than in o m p h a l o c e l e s (Fig. 2). T h e a c c o m p a n y i n g congential anomalities are as a rule restricted to atresias of the bowel and nonrotation. T h e c l e a r l y defined d i f f e r e n c e s induced Duhamel ~ to do an embryologic study, and his conclusions can be summarized as follows: (1) Large omphaloceles are the result of an inborn Journal of Pediatric Surgery, VoI. 13, No. 1 (February), 1978
error in the fetal morphogenesis. They are aberrations in the initial blueprint of the baby. They are in fact "monstrosities," and are therefore o f t e n a c c o m p a n i e d by o t h e r c o n g e n i t a l anomalies. (2) Gastroschisis, on the contrary, is caused by a teratogenic agent during the development of the embryo. It is not an inborn error and is therefore rarely accompanied by other than local anomalies like atresias and nonrotation. Of course it is well known that an external agent in early pregnancy can cause manifold serious malformations. Rubeola and some medicines are notorious in that way. Shaw does not agree with Duhamel, and states his opinion as follows: " T h e available clinical and embryologic evidence strongly suggests that gastrosc h i s i s . . , is the result of an in utero rupture of the membrane covering a hernia of the umbilical cord, either during its normal phase (fifth to tenth week of fetal life) or at a later stage in embryos in which closure of the normally formed umbilical ring has failed to take place. Current concepts of an embryogenesis for gastroschisis distinct from that of hernia of the umbilical cord-omphalocele (author), should be discarded." 1 According to Shaw, there is no difference in cause; only in timing. Thomas and AtwelP have clinical reasons for their view that "gastroschisis is most probably the end result of intra-uterine rupture of an incarcerated hernia into the cord." They substantiate this by the fact, that there is never any muscle mass present between the defect and the cord. Moreover the invariable incidence of a universal mesentery leads them to the concluFrom the Department of Paediatric Surgery, Sophia Children's Hospital and Neonatal Unit, Erasmus University, Rotterdam, The Netherlands. Presented before the X X I V Annual International Congress of the British Association of Paediatric Surgeons, Oslo, Norway, August 2-6, 1977. Address reprint requests to J. A. NoordO'k, M.D., Sophia Children's Hospital and Neonatal Unit, Gordelweg 160, Rotterdam, The Netherlands. 9 1978 by Grune & Stratton, Inc. 0022-3468/78/1301-00 ! lSOl.O0/O 47
48
NOORDIJK AND BLOEMSMA-JONKMAN
Fig. 1.
Omphalocele. The cord emerges from the top of
the sac.
sion that the gut did not herniate through the defect, but rather was denied the opportunity to return to the abdomen to undergo normal rotation and fixation. We also found in all our cases of gastroschisis a non-rotation of the bowel. The accompanying atresias support the theory of Thomas and Atwell. In our series of fourteen patients we once
Fig. 2. site.
Gastroschisis. The cord emerges at its normal
found a total atresia of the small intestine and once a short bowel of about 30 centimeters. Thomas and Atwell give no opinion about the origin of omphaloceles. In an embryologic study, Mtintener 4 comes to the conclusion that in omphaloceles, an incomplete closure of the abdominal wall has taken place with closure of the peritoneum. But in gastroschisis there is a defect of the mesenchyme and the peritoneum remains open. He gives no opinion as to the origin of omphaloceles, but states only that the teratogenic agent that causes an omphalocele should appear before the sixth wk of pregnancy. To cause a gastroschisis, such an agent should do its work only before the eighth week. Mahour 5 states in a "collective review" that "chromosomal abnormalities do not seem to play an important role in the cause of omphalocele." But in the literature, there are clear indications that genetic causes cannot so easily be discarded. Kuvera and Goetz 6 report one family with four consecutive children with omphalocele. These four children have all died. Two had other anomalies as well (spina bifida, cleft palate). The family history, however, is negative apart from a cleft palate in a son of a maternal sister. Osuna and Lindham 7 describe four cases of omphalocele in two generations of the same family. Two of these children survived, but one had Down's syndrome. Autopsy was performed upon only one of the children, but no other anomalies were discovered. The combination of omphalocele and the WiedemannBeckwitz syndrome has also been described by Irving s and others. Rott 9 comes to the conclusion that genetic factors are most important as a cause of omphalocete, but he does not exclude exogenic factors. From all these contradicting opinions we must come to the conclusion that clinically we find important differences between omphalocele and gastroschisis, but the embryologic explanations of these differences do not seem very convincing. Still it is important to know whether there are genetic causes for both omphalocele and gastroschisis, or if perhaps this genetic influence is restricted to omphaloceles only. The answer to this question is most important for giving advice concerning the risk of future pregnancies.
GASTROSCHISlS
49
MATERIALS AND METHODS In this study we have restricted ourselves to those cases of omphalocele and gastroschisis that came to us after January 1, 1970. These patients are better documented than most of the earlier cases and the parents are still interested in the catastrophe, even if the child in question did not survive. We did not include small omphaloceles with a diameter of less than 5 cm. We have treated 51 children with these anomalies. There was usually no doubt whether an omphalocele or a gastroschisis was present; 37 cases were classified as omphalocele, 14 as gastroschisis. Among the omphaloceles was a pair of conjoined twins. These were connected with each other from the cele to the sternum. Separation was not successful because the blood supply of the bowel of child 2 came from child 1. Moreover, there was only one liver, with two gall bladders and two bile duct systems; these discharged in one papilla Vateri only. Only one umbilical vein was present and the ductus venosus went to child 1. There were four umbilical arteries. These conjoined twins were considered as two children. It is interesting to know that in the family of both father and mother normal twins have been reported and that other congenital anomalies were present on the side of both parents. The family history of one of the other children with omphalocele also disclosed a pair of conjoined twins. Three of the 14 gastroschisis patients died, two from septicemia, and one because of a near-total atresia of the bowel. Of the 37 omphaloceles, 18 did not survive. Of a total of 51 patients, 21 died. These mortality figures are about the same as reported in other recent publications (Joppich10 and
Venugopa111). DISCUSSION
Although there seem to be clear differences b e t w e e n o m p h a l o c e l e and g a s t r o s c h i s i s , opinions vary about the etiology of these anomalies. Duhamel states that omphaloceles are the result of an "inborn error" and that gastroschisis is caused by a teratogenic agent. Shaw is convinced that there are no causal differences between omphalocele and gastroschisis and that the clinical differences can be
explained by the age of the fetus at the time of the teratogenic agent. For well-founded genetic advice to parents, it is most important to know if and in which cases a genetic factor is present. For this reason we made a study of the family history of both groups of patients. This study was restricted to the family members in the first and second degree, and to the parents of the child in question. It was thought that if a genetic component was present in cases of both gastroschisis and o m p h a l o c e l e , the f r e q u e n c y of congenital anomalies in the other members of the family should be about the same. This turned out not to be the case. In the families of the omphalocele patients, the number of congenital abnormalities was considerably larger than in the families of gastroschisis patients. In our 14 cases of gastroschisis only from the siblings of one patient were congenital anomalies reported. T h e s e were present both on the side of the father and of the mother. In the 37 cases of omphalocele, congenital anomalies were reported no less than 15 times, in three cases from both the father's and mother's side. This difference is so significant that we can assume that genetic factors play a role in the origin of omphaloceles, whereas this is not the case in gastorschisis. We cannot explain these differences by a time factor alone, as does Shaw. Therefore, with regard to the risk of congenital abnormalities in future pregnancies, we should be more guarded with parents with a child suffering from omphalocele. On the other hand, there seems to be little contraindication for another pregnancy in the case of gastroschisis.
REFERENCES 1. Shaw A: The myth of gastroschisis. J Pediatr Surg 10:235 244, 1975 2. Duhamel B: Embryology of exomphalos and allied malformations. Arch Dis Child 38:142 147, 1963 3. Thomas DFM, Atwell JD: The embryology and surgical management of gastroschisis. Br J Surg 63:893-897, 1976 4. MUntener M: Zur genese der omphalozele und "Gastroschisis" (paraumbilikaler bauchwanddefekt). Z Kinderchir 8:380-390, 1970 5. Mahour GH: Omphalocele--collective review. Surg Gynecol Obstet 143:821-828, 1976
6. Kucera J, Goetz P: Exomphalos in four consecutive pregnancies. Humangenetik 13:58-60, 1971 7. Osuna A, Lindham S: Four cases of omphalocele in two generations of the same family. Clin Genet 9:354-356, 1976 8. Irving IM: Exomphalos with macroglossia: A study of eleven cases. J Pediatr Surg 2:499-507, 1976 9. Rott HD: Zur haufigkeit und ~tiologie der omphalozelen. Z Kinderheilkd 119:133 141, 1975 10. Joppich I: Omphalozele und gastroschisis. MUnch Med Wochenschr 116:1195-1200, 1974 11. Venugopal S, Zachary RB, Spitz L: Exomphalos and gastroschisis. Br J Surg 63:523-525, 1976
different manifestations of the same underlying cause. After studying the family history of 37 patients
with omphalocele end 14 patients with gastroschisis, it seems probable that hereditary factors contribute to the origin of o m p h a l o c e l e s . Such f a c t o r s were not shown in patients with gastroschisis. Therefore genetic evaluation and counselling is advocated for the parents of a child with o m p h a l o c e l e . IN DEX W O R D S : O m p h a l o c e l e ; gastroschisis.
N A R E C E N T A R T I C L E , Shaw I qualified as a " m y t h " the distinction made between gastroschisis and omphalocele. He states that, from a developmental standpoint, categoric separation of these pathologic entities is untenable, even if it has been clinically useful. There is still some confusion about the terminology, and often the concepts of gastroschisis and omphalocele are used indiscriminately, although there are important differences.
I
Omphalocele There is always a sac present, which has or has not been ruptured during birth, and often contains parts of liver, stomach, or spleen (Fig. 1). The umbilical cord always emerges from the top of this sac. The abdominal defect is usually large. M o r e o v e r o m p h a l o c e l e s are o f t e n combined with other serious congenital abnormalities, of which Cardiac anomalies have the greatest influence upon the chance of survival.
Gastroschisis There is never a sac present, and the umbilical cord emerges at its normal site on the abdominal wall, usually to the left of the defect that on the average is much smaller than in o m p h a l o c e l e s (Fig. 2). T h e a c c o m p a n y i n g congential anomalities are as a rule restricted to atresias of the bowel and nonrotation. T h e c l e a r l y defined d i f f e r e n c e s induced Duhamel ~ to do an embryologic study, and his conclusions can be summarized as follows: (1) Large omphaloceles are the result of an inborn Journal of Pediatric Surgery, VoI. 13, No. 1 (February), 1978
error in the fetal morphogenesis. They are aberrations in the initial blueprint of the baby. They are in fact "monstrosities," and are therefore o f t e n a c c o m p a n i e d by o t h e r c o n g e n i t a l anomalies. (2) Gastroschisis, on the contrary, is caused by a teratogenic agent during the development of the embryo. It is not an inborn error and is therefore rarely accompanied by other than local anomalies like atresias and nonrotation. Of course it is well known that an external agent in early pregnancy can cause manifold serious malformations. Rubeola and some medicines are notorious in that way. Shaw does not agree with Duhamel, and states his opinion as follows: " T h e available clinical and embryologic evidence strongly suggests that gastrosc h i s i s . . , is the result of an in utero rupture of the membrane covering a hernia of the umbilical cord, either during its normal phase (fifth to tenth week of fetal life) or at a later stage in embryos in which closure of the normally formed umbilical ring has failed to take place. Current concepts of an embryogenesis for gastroschisis distinct from that of hernia of the umbilical cord-omphalocele (author), should be discarded." 1 According to Shaw, there is no difference in cause; only in timing. Thomas and AtwelP have clinical reasons for their view that "gastroschisis is most probably the end result of intra-uterine rupture of an incarcerated hernia into the cord." They substantiate this by the fact, that there is never any muscle mass present between the defect and the cord. Moreover the invariable incidence of a universal mesentery leads them to the concluFrom the Department of Paediatric Surgery, Sophia Children's Hospital and Neonatal Unit, Erasmus University, Rotterdam, The Netherlands. Presented before the X X I V Annual International Congress of the British Association of Paediatric Surgeons, Oslo, Norway, August 2-6, 1977. Address reprint requests to J. A. NoordO'k, M.D., Sophia Children's Hospital and Neonatal Unit, Gordelweg 160, Rotterdam, The Netherlands. 9 1978 by Grune & Stratton, Inc. 0022-3468/78/1301-00 ! lSOl.O0/O 47
48
NOORDIJK AND BLOEMSMA-JONKMAN
Fig. 1.
Omphalocele. The cord emerges from the top of
the sac.
sion that the gut did not herniate through the defect, but rather was denied the opportunity to return to the abdomen to undergo normal rotation and fixation. We also found in all our cases of gastroschisis a non-rotation of the bowel. The accompanying atresias support the theory of Thomas and Atwell. In our series of fourteen patients we once
Fig. 2. site.
Gastroschisis. The cord emerges at its normal
found a total atresia of the small intestine and once a short bowel of about 30 centimeters. Thomas and Atwell give no opinion about the origin of omphaloceles. In an embryologic study, Mtintener 4 comes to the conclusion that in omphaloceles, an incomplete closure of the abdominal wall has taken place with closure of the peritoneum. But in gastroschisis there is a defect of the mesenchyme and the peritoneum remains open. He gives no opinion as to the origin of omphaloceles, but states only that the teratogenic agent that causes an omphalocele should appear before the sixth wk of pregnancy. To cause a gastroschisis, such an agent should do its work only before the eighth week. Mahour 5 states in a "collective review" that "chromosomal abnormalities do not seem to play an important role in the cause of omphalocele." But in the literature, there are clear indications that genetic causes cannot so easily be discarded. Kuvera and Goetz 6 report one family with four consecutive children with omphalocele. These four children have all died. Two had other anomalies as well (spina bifida, cleft palate). The family history, however, is negative apart from a cleft palate in a son of a maternal sister. Osuna and Lindham 7 describe four cases of omphalocele in two generations of the same family. Two of these children survived, but one had Down's syndrome. Autopsy was performed upon only one of the children, but no other anomalies were discovered. The combination of omphalocele and the WiedemannBeckwitz syndrome has also been described by Irving s and others. Rott 9 comes to the conclusion that genetic factors are most important as a cause of omphalocete, but he does not exclude exogenic factors. From all these contradicting opinions we must come to the conclusion that clinically we find important differences between omphalocele and gastroschisis, but the embryologic explanations of these differences do not seem very convincing. Still it is important to know whether there are genetic causes for both omphalocele and gastroschisis, or if perhaps this genetic influence is restricted to omphaloceles only. The answer to this question is most important for giving advice concerning the risk of future pregnancies.
GASTROSCHISlS
49
MATERIALS AND METHODS In this study we have restricted ourselves to those cases of omphalocele and gastroschisis that came to us after January 1, 1970. These patients are better documented than most of the earlier cases and the parents are still interested in the catastrophe, even if the child in question did not survive. We did not include small omphaloceles with a diameter of less than 5 cm. We have treated 51 children with these anomalies. There was usually no doubt whether an omphalocele or a gastroschisis was present; 37 cases were classified as omphalocele, 14 as gastroschisis. Among the omphaloceles was a pair of conjoined twins. These were connected with each other from the cele to the sternum. Separation was not successful because the blood supply of the bowel of child 2 came from child 1. Moreover, there was only one liver, with two gall bladders and two bile duct systems; these discharged in one papilla Vateri only. Only one umbilical vein was present and the ductus venosus went to child 1. There were four umbilical arteries. These conjoined twins were considered as two children. It is interesting to know that in the family of both father and mother normal twins have been reported and that other congenital anomalies were present on the side of both parents. The family history of one of the other children with omphalocele also disclosed a pair of conjoined twins. Three of the 14 gastroschisis patients died, two from septicemia, and one because of a near-total atresia of the bowel. Of the 37 omphaloceles, 18 did not survive. Of a total of 51 patients, 21 died. These mortality figures are about the same as reported in other recent publications (Joppich10 and
Venugopa111). DISCUSSION
Although there seem to be clear differences b e t w e e n o m p h a l o c e l e and g a s t r o s c h i s i s , opinions vary about the etiology of these anomalies. Duhamel states that omphaloceles are the result of an "inborn error" and that gastroschisis is caused by a teratogenic agent. Shaw is convinced that there are no causal differences between omphalocele and gastroschisis and that the clinical differences can be
explained by the age of the fetus at the time of the teratogenic agent. For well-founded genetic advice to parents, it is most important to know if and in which cases a genetic factor is present. For this reason we made a study of the family history of both groups of patients. This study was restricted to the family members in the first and second degree, and to the parents of the child in question. It was thought that if a genetic component was present in cases of both gastroschisis and o m p h a l o c e l e , the f r e q u e n c y of congenital anomalies in the other members of the family should be about the same. This turned out not to be the case. In the families of the omphalocele patients, the number of congenital abnormalities was considerably larger than in the families of gastroschisis patients. In our 14 cases of gastroschisis only from the siblings of one patient were congenital anomalies reported. T h e s e were present both on the side of the father and of the mother. In the 37 cases of omphalocele, congenital anomalies were reported no less than 15 times, in three cases from both the father's and mother's side. This difference is so significant that we can assume that genetic factors play a role in the origin of omphaloceles, whereas this is not the case in gastorschisis. We cannot explain these differences by a time factor alone, as does Shaw. Therefore, with regard to the risk of congenital abnormalities in future pregnancies, we should be more guarded with parents with a child suffering from omphalocele. On the other hand, there seems to be little contraindication for another pregnancy in the case of gastroschisis.
REFERENCES 1. Shaw A: The myth of gastroschisis. J Pediatr Surg 10:235 244, 1975 2. Duhamel B: Embryology of exomphalos and allied malformations. Arch Dis Child 38:142 147, 1963 3. Thomas DFM, Atwell JD: The embryology and surgical management of gastroschisis. Br J Surg 63:893-897, 1976 4. MUntener M: Zur genese der omphalozele und "Gastroschisis" (paraumbilikaler bauchwanddefekt). Z Kinderchir 8:380-390, 1970 5. Mahour GH: Omphalocele--collective review. Surg Gynecol Obstet 143:821-828, 1976
6. Kucera J, Goetz P: Exomphalos in four consecutive pregnancies. Humangenetik 13:58-60, 1971 7. Osuna A, Lindham S: Four cases of omphalocele in two generations of the same family. Clin Genet 9:354-356, 1976 8. Irving IM: Exomphalos with macroglossia: A study of eleven cases. J Pediatr Surg 2:499-507, 1976 9. Rott HD: Zur haufigkeit und ~tiologie der omphalozelen. Z Kinderheilkd 119:133 141, 1975 10. Joppich I: Omphalozele und gastroschisis. MUnch Med Wochenschr 116:1195-1200, 1974 11. Venugopal S, Zachary RB, Spitz L: Exomphalos and gastroschisis. Br J Surg 63:523-525, 1976