Ham. Genet. 32, 221--223 (1976) © by Springer-Verlag 1976
Exomphalos and Trisomy 18 Syndrome R e p o r t o f T w o Cases J a n Zi~ka, P e t r Bali~ek, E v a Pokorn&, K a t e } i n a D o s t a l i k o v ~ a n d Marie K o d o u s k o v g Cytogenetic Laboratory, Departments of Pediatrics and Pathology, Faculty Hospital, Hradec KrAlov6, Czechoslovakia ]~eceived December 16, 1975
Summary. A large exomphalos was found in two infants with a clinically and cytogenetically typical picture of trisomy 18 syndrome. In addition one infant was a case of male pseudohermaphroditism.
T h e p h e n o t y p i c characteristics of t h e t r i s o m y 18 s y n d r o m e h a v e been well described. T h e classical clinical s p e c t r u m has been w i d en ed b y t h e reports of phocomelia, biliary atresia, l u m b a r meningocele, and o t h er s y m p t o m s . Only except i o n a l l y was e x o m p h a l o s m e n t i o n e d in this syndrome. Th e purpose of this p ap er is t o describe 2 cases w i t h e x o m p h a l o s a n d t r i s o m y 18 syndrome.
Case Histories Case 1. The male child was born at 36 weeks' gestation. The mother was a 26-year-old gravida 4, para 2. She had two interruptions, no spontaneous abortion. The father was 25 years old at the time of child's birth. The parents and a 3-year-old sister were healthy, there was no history of congenital malformations and consanguinity in the family. The mother was probably exposed to rubella 1 month before conception but she had no rash following her exposure. Fetal movements were feeble and polyhydramnios was noted at delivery. The placenta weighed 200 g, the umbilical cord was short, and two umbilical arteries were present. The patient's birth weight was 1350 g, and length 37 cm. The following malformations were observed on examination: low set and deformed ears, microretrognathia, short sternum, hypoplastic nails, flexion contractures of the fingers, undescended testes, right single palmar crease, short dorsiflexed big toes, one flexion crease on 2, 3, 4 fingers, limited hip abduction, and large exomphalos which contained the loops of the small intestine (Fig. 1). The infant underwent surgical correction of the exomphalos and expired 12 h after operation due to cardiorespiratory complications. Necropsy showed the following additional malformations: hypoplastic thymus, persistent ductus arteriosus, coarctation of the aorta, bicuspid pulmonic and aortic valves, and Meckel's diverticulum. Chromosome analysis of peripheral blood revealed a trisomy of chromosome 18 identified with G-banding technique. Karyotypes of the parents and the sister were normal. Case 2. The patient, a male infant, was born to a 21-year-old, gravida 2, para 2 female at 38 weeks' gestation. The father was 25 years of age. During the last month of the pregnancy the mother was treated for a tapeworm. Pregnancy was complicated by hydramnios. Delivery was by cesarean section. The baby weighed 2220 g and measured 43 cm. The placenta weighed 400 g, the umbilical cord was not examined. The examination of the infant showed the following
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Fig. 1. Case 1. At 1 day of age Fig. 2. Case 2. Post-mortem photograph. Exomphalos after surgical correction
abnormalities: low-set malformed ears, micrognathia, webbing of the neck, flexion deformity of fingers, hypoplastie nails, horizontal palmar crease, cryptorchidism and giant exomphalos which contained the liver, the small, and a part of the large intestine (Fig. 2). The baby died 3 days after operation and the autopsy findings were as follows: foramen ovale aperture, interventricular septal defect, bicuspid pulmonary and aortic valves, und hydroureter bilaterally. In addition to the representative post-mortem findings, abnormalities of the internal genitalia were observed. The testes occupied the position of the ovaries and the uterus was present in the absence of the vagina. The external genitalia were of male type. The penis was normally formed, the scrotum was smaller. Chromosome analysis carried out on a microculture of peripheral leukocytes revealed a modal number of 47 chromosomes with an extra chromosome in the group 18 in the traditional and C-band karyotypes. Blood was drawn by cardiac puncture immediately following death. The karyotypes and dermatoglyphic findings of the father and mother were normal. The family history was nnremarkable, revealed no abortions, stillbirths, or congenital abnormalities. The elder sister was healthy.
Discussion B o t h i n f a n t s showed t y p i c a l clinical a n d necropsy findings of t r i s o m y 18 syndrome a n d the diagnosis was confirmed b y Q- a n d C-band analysis. E x o m p h a l o s in b o t h cases is a quite u n c o m m o n finding a n d has n o t been reported i n reviews of the t r i s o m y 18 syndrome. To our knowledge one probable case of 17--18 t r i s o m y s y n d r o m e with exomphalos was described b y K a j i i et al. (t964), a n d a n o t h e r case
Exoraphalos and Trisomy 18 Syndrome
223
with omphaloeele and partial 18 trisomy resulting from familial B/18 translocation was reported by Eriksson et al. (1971). I f one accepts the estimated incidence of about 0.08 per 1000 live births for trisomy 18 (Nielsen, 1975) and about 0.18 per 1000 for omphalocele (Bock and Zimmerman, 1967) the coincidence of both conditions could theoretically be expected in about 0.0144 per 106 live births. The fact that we observed both conditions twice among 7 of our cases of trisomy 18 syndrome does not rule out chance, but it seems also reasonable to assume more than a coincidental relationship between trisomy 18 syndrome and exomphalos. Four of our cases of trisomy 18 syndrome were born in the period 1965--1968. Two cases with exomphalos in the year 1974, the remaining one case in the year 1975. Our group is too small to study the seasonal and time variations in birth of children with trisomy 18 syndrome. However, the clustering of our cases in the period 1965--1968 and in the years 1974--1975 is remarkable. The coincidence of trisomy 18 syndrome and male pseudohermaphroditism in one case is of interest.
References Bock, It. B., Zimmerman, J. H. : Study of selected congenital anomalies in Pennsylvania. Publ. Hlth Rep. (Wash.) 82, 446--450 (1967) Eriksson, B., Fraccaro, M., Hulten, ~[aj., Lindsten, J., Thoren, C., Tiepolo, L.: Structural abnormalities of chromosome 18. II. Two familial translocations, B/18 and 16/18, ascertained through unbalanced forms. Ann. G@n4t. 14, 281--290 (1971) Kajii, T., Oikawa, K., Itakura, K., Ohsawa, T. : A probable 17--18 trisomy syndrome with phocomelia, exomphalos, and agenesis of hemidiaphragm. Arch. Dis. Childh. 39, 519--522 (1964) Nielsen, J. : Chromosome examination of newborn children. Purpose and ethical aspects. Humangenetik 26, 215--222 (1975) Dr. J. Zi~ka Cytogenetic Laboratory Department of Pediatrics Faculty Hospital 500 36 Hradec Kr£1ov4 Czechoslovakia
Exomphalos and Trisomy 18 Syndrome R e p o r t o f T w o Cases J a n Zi~ka, P e t r Bali~ek, E v a Pokorn&, K a t e } i n a D o s t a l i k o v ~ a n d Marie K o d o u s k o v g Cytogenetic Laboratory, Departments of Pediatrics and Pathology, Faculty Hospital, Hradec KrAlov6, Czechoslovakia ]~eceived December 16, 1975
Summary. A large exomphalos was found in two infants with a clinically and cytogenetically typical picture of trisomy 18 syndrome. In addition one infant was a case of male pseudohermaphroditism.
T h e p h e n o t y p i c characteristics of t h e t r i s o m y 18 s y n d r o m e h a v e been well described. T h e classical clinical s p e c t r u m has been w i d en ed b y t h e reports of phocomelia, biliary atresia, l u m b a r meningocele, and o t h er s y m p t o m s . Only except i o n a l l y was e x o m p h a l o s m e n t i o n e d in this syndrome. Th e purpose of this p ap er is t o describe 2 cases w i t h e x o m p h a l o s a n d t r i s o m y 18 syndrome.
Case Histories Case 1. The male child was born at 36 weeks' gestation. The mother was a 26-year-old gravida 4, para 2. She had two interruptions, no spontaneous abortion. The father was 25 years old at the time of child's birth. The parents and a 3-year-old sister were healthy, there was no history of congenital malformations and consanguinity in the family. The mother was probably exposed to rubella 1 month before conception but she had no rash following her exposure. Fetal movements were feeble and polyhydramnios was noted at delivery. The placenta weighed 200 g, the umbilical cord was short, and two umbilical arteries were present. The patient's birth weight was 1350 g, and length 37 cm. The following malformations were observed on examination: low set and deformed ears, microretrognathia, short sternum, hypoplastic nails, flexion contractures of the fingers, undescended testes, right single palmar crease, short dorsiflexed big toes, one flexion crease on 2, 3, 4 fingers, limited hip abduction, and large exomphalos which contained the loops of the small intestine (Fig. 1). The infant underwent surgical correction of the exomphalos and expired 12 h after operation due to cardiorespiratory complications. Necropsy showed the following additional malformations: hypoplastic thymus, persistent ductus arteriosus, coarctation of the aorta, bicuspid pulmonic and aortic valves, and Meckel's diverticulum. Chromosome analysis of peripheral blood revealed a trisomy of chromosome 18 identified with G-banding technique. Karyotypes of the parents and the sister were normal. Case 2. The patient, a male infant, was born to a 21-year-old, gravida 2, para 2 female at 38 weeks' gestation. The father was 25 years of age. During the last month of the pregnancy the mother was treated for a tapeworm. Pregnancy was complicated by hydramnios. Delivery was by cesarean section. The baby weighed 2220 g and measured 43 cm. The placenta weighed 400 g, the umbilical cord was not examined. The examination of the infant showed the following
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Fig. 1. Case 1. At 1 day of age Fig. 2. Case 2. Post-mortem photograph. Exomphalos after surgical correction
abnormalities: low-set malformed ears, micrognathia, webbing of the neck, flexion deformity of fingers, hypoplastie nails, horizontal palmar crease, cryptorchidism and giant exomphalos which contained the liver, the small, and a part of the large intestine (Fig. 2). The baby died 3 days after operation and the autopsy findings were as follows: foramen ovale aperture, interventricular septal defect, bicuspid pulmonary and aortic valves, und hydroureter bilaterally. In addition to the representative post-mortem findings, abnormalities of the internal genitalia were observed. The testes occupied the position of the ovaries and the uterus was present in the absence of the vagina. The external genitalia were of male type. The penis was normally formed, the scrotum was smaller. Chromosome analysis carried out on a microculture of peripheral leukocytes revealed a modal number of 47 chromosomes with an extra chromosome in the group 18 in the traditional and C-band karyotypes. Blood was drawn by cardiac puncture immediately following death. The karyotypes and dermatoglyphic findings of the father and mother were normal. The family history was nnremarkable, revealed no abortions, stillbirths, or congenital abnormalities. The elder sister was healthy.
Discussion B o t h i n f a n t s showed t y p i c a l clinical a n d necropsy findings of t r i s o m y 18 syndrome a n d the diagnosis was confirmed b y Q- a n d C-band analysis. E x o m p h a l o s in b o t h cases is a quite u n c o m m o n finding a n d has n o t been reported i n reviews of the t r i s o m y 18 syndrome. To our knowledge one probable case of 17--18 t r i s o m y s y n d r o m e with exomphalos was described b y K a j i i et al. (t964), a n d a n o t h e r case
Exoraphalos and Trisomy 18 Syndrome
223
with omphaloeele and partial 18 trisomy resulting from familial B/18 translocation was reported by Eriksson et al. (1971). I f one accepts the estimated incidence of about 0.08 per 1000 live births for trisomy 18 (Nielsen, 1975) and about 0.18 per 1000 for omphalocele (Bock and Zimmerman, 1967) the coincidence of both conditions could theoretically be expected in about 0.0144 per 106 live births. The fact that we observed both conditions twice among 7 of our cases of trisomy 18 syndrome does not rule out chance, but it seems also reasonable to assume more than a coincidental relationship between trisomy 18 syndrome and exomphalos. Four of our cases of trisomy 18 syndrome were born in the period 1965--1968. Two cases with exomphalos in the year 1974, the remaining one case in the year 1975. Our group is too small to study the seasonal and time variations in birth of children with trisomy 18 syndrome. However, the clustering of our cases in the period 1965--1968 and in the years 1974--1975 is remarkable. The coincidence of trisomy 18 syndrome and male pseudohermaphroditism in one case is of interest.
References Bock, It. B., Zimmerman, J. H. : Study of selected congenital anomalies in Pennsylvania. Publ. Hlth Rep. (Wash.) 82, 446--450 (1967) Eriksson, B., Fraccaro, M., Hulten, ~[aj., Lindsten, J., Thoren, C., Tiepolo, L.: Structural abnormalities of chromosome 18. II. Two familial translocations, B/18 and 16/18, ascertained through unbalanced forms. Ann. G@n4t. 14, 281--290 (1971) Kajii, T., Oikawa, K., Itakura, K., Ohsawa, T. : A probable 17--18 trisomy syndrome with phocomelia, exomphalos, and agenesis of hemidiaphragm. Arch. Dis. Childh. 39, 519--522 (1964) Nielsen, J. : Chromosome examination of newborn children. Purpose and ethical aspects. Humangenetik 26, 215--222 (1975) Dr. J. Zi~ka Cytogenetic Laboratory Department of Pediatrics Faculty Hospital 500 36 Hradec Kr£1ov4 Czechoslovakia
