American Journal of Medical Genetics 44:624-627 (1992)
~
Familial Omphalocele: Considerations in Genetic Counseling Peter G. Pryde, Anne Greb, Nelson B. Isada, Mark B. Johnson, Michael Klein, and Mark I. Evans Division of Reproductive Genetics, Departments of Obstetrics and Gynecology, Hutzel HospitallWayne State University (P.G.P.,A.G., N.B.I., M.B.J., M.I.E.), and Pediatric General Surgery, Childrens Hospital of Michigan (M.K.), Wayne State University, Detroit, Michigan
Nonsyndromal omphalocele is generally regarded as a sporadic malformation. Recurrence risk is considered negligible. We report on a patient in whom 5 consecutive pregnancies (by 2 separate nonconsanguineous partners) were complicated by omphalocele as an isolated defect. Neither the patient nor her partners had history of relatives with omphalocele, although the patient’s brother and his son had large umbilical hernias requiring repair in infancy. Some familial cases of nonsyndromal omphalocele have been previously reported; most such pedigrees s u g gest vertical transmission, although there are a few cases with only a single generation involved. In our case, the multigenerational finding of ventral wall hernias makes an autosoma1dominant mechanism with variable expressivity a tenable explanation. The collected instances of familial nonsyndromal omphalocele emphasize omphalocele heterogeneity and caution in counseling recurrence risks. o 1992 Wiley-Liss, Inc.
negligible. At least 17 cases of familial nonsyndromal omphalocele have been published (Table I); however, most authors agree that these are exceptional cases. We have observed a young woman in whom all 5 of her progeny were affected with omphalocele as an isolated defect. The fact that familial omphalocele does occur, albeit rare, mandates that the possibility be acknowledged in discussions of genetic cause and recurrence risks.
CLINICAL REPORT The patient was referred for genetic counselling during her fifth pregnancy following 4 previous gestations affected by isolated omphalocele. She had been evaluated by her referring physician at 20 weeks of gestation when ultrasound examination of the fetus demonstrated findings consistent with an isolated large omphalocele. Amniocentesis was performed documenting normal amniotic fluid a-fetoprotein, and acetylcholinesterase. The karyotype was 46,XX. At the time of her consultation, the patient was a t 24 weeks of gestation (Fig. 1) and arrangements were made for immediate omphalocele repair after elective repeat cesarean section at 37 weeks of gestation. Unfortunately, she went into spontaneous KEY WORDS: omphalocele, familial ompremature labor and was delivered at 30.5 weeks gestaphalocele, ventral wall detion by cesarean section at the referring institution. The fects, autosomal dominant 1,650 g female infant underwent uncomplicated repair inheritance, genetic counselon the following day but died on the second day of respiling ratory distress syndrome. The family pedigree is summarized in (Fig. 2). Her first 3 pregnancies were fathered by a previous nonconsanguineous partner. The fourth and fifth pregnancies INTRODUCTION Isolated nonsyndromal omphalocele is generally re- were fathered by her present partner (also noncongarded as an uncommon and sporadic malformation sanguineous). Her first pregnancy was complicated by [Baird and MacDonald, 1981; Czeizel and Vitez, 1981; preterm labor and precipitous delivery at 25 weeks of Hirata et al., 19901,and recurrence risk is reported to be gestation. The 680 g infant female had a nonsyndromal omphalocele,and died on day 1prematurity. During the second pregnancy the patient was sent to our institution for early evaluation. Ultrasound examination at 14 weeks of gestation demonstrated an isolated large Received for publication December 16,1991;revision received omphalocele (Fig. 3). Early amniocentesis was perApril 20, 1992. formed, and the karyotype was 46,XX. At 16 weeks of Address reprint request to Peter G. Ryde, M.D., Division of gestation a spontaneous abortion occurred. The third Reproductive Genetics, Department of Obstetrics/Gynecology, pregnancy was marked by a late presentation for prenaHutzel HospitaINayne State University, 4707 St. Antoine Boulevard, Detroit, MI 48021. tal care. At 29 weeks gestation the patient went into 0 1992 Wiley-Liss, Inc.
Familial Omphalocele
625
TABLE I. Previously Reported Cases of Familial Omphalocele Reference %cot and Gelle [1936] Benson et al. [1949] McKeown et al. [1952] Rothenberg and Barnett 119571 Yuzepe and Johnson [1968] Rott and Truckenbrodt [1974] Osuna and Lindham [1976] Havalad et al. [1979] DiLiberti [1982] Kucera and Goetz [19711 Czeizel [19791 Kapur et al. [1980] Lowry and Baird [1982] Lurie and Ilyina [1984] Lurie (cont) Lurie (cont) Steele and Nevin [1985]
Case #
No. affected
8
3 2 3 2 2 2 3” 4
9 10 11 12 13 14
4 2 2 2 2
15
2“
1 2 3 4 5 6 7
Vertical transmission No No Yes No No No Yes Yes Yes No Yes Yes No No Yes Yes Yes
Other anomalies Encephalocele (113) None None None MZ Twins None None Small VSD W 4 ) None Multiple defects (214) None None None Spina bifida (1/2) Multiple defects (1/2) Multiple defects (1/3) None
2b
16 3* 17 7 a One additional infant with omphalocele excluded due to diagnosis of trisomy 21. Three previous generations each with a member having large umbilical hernias requiring surgical repair (two of whom also had other ventral wall defects as well). ‘Father of affected infants had large inguinal hernia repaired in childhood, and a ventral wall hernia repaired as a n adult. Several maternal relatives required childhood surgery for large umbilical hernias.
labor. After failed tocolysis a classical cesarean section was performed due to breech presentation. The 1,500 g infant boy was found t o have an isolated omphalocele which was repaired. However, after an unstable neonatal period he died a t age 5 months. During pregnancy 4, the patient again presented in premature labor. She failed tocolysis and was delivered, at 30 weeks of gestation, by repeat cesarean section. The 1,590 g male infant had a large omphalocelewhich was repaired, but he died several days later of complications related to prematurity.
MacDonald, 1981; Czeizel and Vitez, 19811. Excluding cases affected by multiple malformations (60-70%) [Benacerrafe et al., 1990; Gilbert and Nicolaides, 19871 and/or chromosome anomalies (4044%) [Gilbert and Nicolaides, 1987; Hughes et al., 19891, the incidence of isolated omphalocelecan be estimated to be on the order of 0.5/10,000. Because even these selected cases are generally regarded as sporadic, recurrence risks are typically counselled to be negligible. Our case, and several previously documented cases suggest that nonsyndroma1 omphalocele is in fact heterogeneous and in some families recurrence risks may be as high as 50%. DISCUSSION The reported cases of familial omphalocele (excluding Large population-based registries have demonstrated syndromal cases such as Beckwith-Wiedemann synthat omphalocele is typically a sporadic congenital drome) are summarized in Table I. Several trends inianomaly affecting 1to 2 in 10,000 live-births [Baird and tially suggested by DiLiberti [19821 are evident. First, in contrast to the entire group of fetuses affected by omphalocele,the familial cases have a lower incidence of associated chromosomal or structural anomalies. In the ........ ........ ........ ........ ........ ........ ........ ........
..... ....... ........ ........ ........ .......
0-0
I
......
I1 2
1
3
Fig. 1. Ultrasound performed at 24 weeks of gestation during fifth pregnancy demonstrating fetal omphalocele. Note midline abdominal defect with clear visualization of membrane surrounding extruded abdominal contents.
5
3
4
6
Fig. 2. Pedigree: W 0 ,omphalocele; 00,family members known to have had “large umbilical hernias” requiring repair in infancy; 0 0 , family members about whom status regarding ventral wall hernias is unknown.
626
Pryde et al.
mechanisms or in some cases chance alone might be operating. Our patient had all 5 of her progeny affected with isolated omphalocele. Although she had no previous family history of true omphalocele there were first and second degree relatives with large umbilical hernias. Previous authors [DiLiberti, 1982; Lurie and Ilyina, 19843have noted the occurrence of umbilical, inguinal, and ventral wall hernias in “unaffected” relatives in families in which omphalocele appeared to be transmitted in a vertical fashion. DiLiberty [19821postulated an autosomal dominant primary defect in abdominal wall structure. He suggested that omphalocele represented the full expression of the defect, while abdominal wall hernias represented affected individuals having a milder expression of the same primary defect. On the other hand, Hinrichsen [19901has emphasized distinct pathogenetic mechanisms, particularly in timing, in the development of true omphaloceleversus umbilical hernia. According t o his model omphalocele is caused by failure of closure of the lateral ectomesodermic folds occurring between 3 and 4 weeks of gestation, in contrast to umbilical hernia which is a true hernia through a defect in the umbilical ring occurring between 8 and 10 weeks of gestation. This model might suggest that those families having members in multiple generations seemingly affected with “omphalocele”in some cases, and “umbilical hernia” in others, may in fact represent cases of “familial umbilical hernia” in which the most extremely affected individuals have umbilical hernias of such a severity that they are neonatally indistinguishable from omphalocele. With present data and diagnostic limitations it is not possible to determine with certainty the genetic cause of Fig. 3. Ultrasound at 14 weeks gestation during second pregnancy. omphalocele in the familial cases reviewed. OmDespite poorer resolution afforded by equipment available at the time, a large midline ventral wall defect (marked by calipers) is imaged on phalocele as a whole does appear to be sporadic in occurthis transverse view at the level of the fetal umbilicus. Fetal spine can rence. However, there can be little doubt that in many of be seen on the left of the figure for orientation. the reported familial cases there is an important genetic contribution. In our case, the finding of umbilical her52 affected fetuses accumulated to date (5 from our case, nias requiring repair in the patient’s brother and his son plus 47 from the 17 families previously reported) there makes an autosomal dominant mechanism with variwere 7 fetuses (13.5%) affected by other anomalies able expressivity a tenable explanation. The collected [Havalad et al., 1979; Kucera and Goetz, 1971; Lurie instances of familial nonsyndromal omphalocele emand Ilyina, 1984; Pucot and Gelle, 19361.While this is a phasize genetic heterogeneity in its cause, and must be substantial increase in structural anomalies over the 3 considered when counselling recurrence risks. to 4% rate which would be expected in the general population, it is much less than the 60 to 70% rate reported in REFERENCES the omphalocele group as a whole. Baird PA, MacDonald EC (1981):An epidemiologic study of congenital Also observed is a tendency in familial cases for a malformations of the anterior abdominal wall in more than half a vertical mode of transmission. In the 17 previously remillion consecutive live births. Am J Hum Genet 33:470-478. ported families, 9 had omphalocele-affectedrelatives in Benacerraf BR, Saltzman DH, Estroff JA, Frigoletto FD Jr (1990): Abnormal karyotype of fetuses with omphalocele: Prediction based more than one generation [Czeizel, 1979; DiLiberti, on omphalocele contents. Obstet Gynecol 75:317-319. 1982;Havaladet al., 1979;Kapur et al., 1971;Lurie and Benson CD, Penberthy GC, Hill J (1949): Hernia into the umbilical cord Ilyina, 1984; McKeown et al., 1952; Osuna and Linand omphalocele in the newborn. Arch Surg 58:833-847. dham, 19761. In one of these 9 families only males were affected, and there were no instances of transmission of Czeizel A (1979): Recurrence risk of omphalocele. Lancet 2:470. A, Vitez M (1981): Etiologic study of omphalocele. Hum Genet the trait by affected males suggesting X-linked inheri- Czeizel 58390-395. tance [Havalad et al., 19791.In the remaining 8 families, DiLiberti J H (1982):Familial omphalocele: Analysis of risk factors and pedigrees suggested autosomal dominant inheritance. case report. Am J Med Genet 13:263-268. The families affected in a single generation (8 of the Gilbert WM, Nicolaides KH (1987): Fetal omphalocele: Associatedmalformations and chromosomal defects. Obstet Gynecol70:633-635. published i 7 families) might represent cases of autosoma1 recessive inheritance, although multifactorial Havalad S, Noblett H, Speidel BD (1979): familial occurrence of
Familial Omphalocele omphalocele suggesting sex-linked inheritance. Arch Dis Child 54:142- 151. Hinrichsen KV (1990): “Human Embryologie.” New York; SpringerVerlag, p 145. Hirata GI, Medearis AL, Platt LD (1990):Fetal abdominal abnormalities associated with genetic syndromes. Clin Perinat 17:675-702. Huges MD, Nyberg DA, Mack LA, Pretorious DH (1989): Fetal omphalocele: Prenatal ultrasound detection of concurrent anomalies and other predictors of outcome. Radiology 173:371-376. Kapur S, Higgins JV, Scott-Emuakpor AB, Dolanski EA (1971): Omphalocele in half-siblings. Clin Genet 1358-60. Kucera J, Goetz P (1971):Exomphalos in four consecutive pregnancies. Hum Genet 13:58-60. Lowry RB, Baird PA (1982): Familial gastroschisis and omphalocele. Am J Hum Genet 3 4 5 1 7 4 1 8 . Lurie IW, Ilyina HG (1984): Familial omphalocele and recurrence risks. Am J Med Genet 17541-543.
627
McKeown T, MacMahon B Record RG (1952): An investigation of 69 cases of exomphalos. Am J Hum Gen 5:168-173. Osuna A, Lindham S (1976):Four cases of omphalocele in two generations of the same family. Clin Genet 9:354-356. Pucot H, Gelle P (1936): Hernie ombilicale embryonnaire recidivante chez 3 foetus successifs. Bull SOC Obstet Gynecol 25296-297. Rothenberg RE, Barnett (1957): Omphalocele in siblings. Arch Surg 75:131-134. Rott HD, Truckenbrodt H (1974): Familial occurrence of omphalocele. Humangenetik 24:259-260. Steele K, Nevin NC (1985): Familial omphalocele. Ulster Med J 54: 214-215. Yuzepe A, Johnson HD (1968): Omphalocele affecting both members of a twin pregnancy. Can Med Assoc J 99:374-376.
~
Familial Omphalocele: Considerations in Genetic Counseling Peter G. Pryde, Anne Greb, Nelson B. Isada, Mark B. Johnson, Michael Klein, and Mark I. Evans Division of Reproductive Genetics, Departments of Obstetrics and Gynecology, Hutzel HospitallWayne State University (P.G.P.,A.G., N.B.I., M.B.J., M.I.E.), and Pediatric General Surgery, Childrens Hospital of Michigan (M.K.), Wayne State University, Detroit, Michigan
Nonsyndromal omphalocele is generally regarded as a sporadic malformation. Recurrence risk is considered negligible. We report on a patient in whom 5 consecutive pregnancies (by 2 separate nonconsanguineous partners) were complicated by omphalocele as an isolated defect. Neither the patient nor her partners had history of relatives with omphalocele, although the patient’s brother and his son had large umbilical hernias requiring repair in infancy. Some familial cases of nonsyndromal omphalocele have been previously reported; most such pedigrees s u g gest vertical transmission, although there are a few cases with only a single generation involved. In our case, the multigenerational finding of ventral wall hernias makes an autosoma1dominant mechanism with variable expressivity a tenable explanation. The collected instances of familial nonsyndromal omphalocele emphasize omphalocele heterogeneity and caution in counseling recurrence risks. o 1992 Wiley-Liss, Inc.
negligible. At least 17 cases of familial nonsyndromal omphalocele have been published (Table I); however, most authors agree that these are exceptional cases. We have observed a young woman in whom all 5 of her progeny were affected with omphalocele as an isolated defect. The fact that familial omphalocele does occur, albeit rare, mandates that the possibility be acknowledged in discussions of genetic cause and recurrence risks.
CLINICAL REPORT The patient was referred for genetic counselling during her fifth pregnancy following 4 previous gestations affected by isolated omphalocele. She had been evaluated by her referring physician at 20 weeks of gestation when ultrasound examination of the fetus demonstrated findings consistent with an isolated large omphalocele. Amniocentesis was performed documenting normal amniotic fluid a-fetoprotein, and acetylcholinesterase. The karyotype was 46,XX. At the time of her consultation, the patient was a t 24 weeks of gestation (Fig. 1) and arrangements were made for immediate omphalocele repair after elective repeat cesarean section at 37 weeks of gestation. Unfortunately, she went into spontaneous KEY WORDS: omphalocele, familial ompremature labor and was delivered at 30.5 weeks gestaphalocele, ventral wall detion by cesarean section at the referring institution. The fects, autosomal dominant 1,650 g female infant underwent uncomplicated repair inheritance, genetic counselon the following day but died on the second day of respiling ratory distress syndrome. The family pedigree is summarized in (Fig. 2). Her first 3 pregnancies were fathered by a previous nonconsanguineous partner. The fourth and fifth pregnancies INTRODUCTION Isolated nonsyndromal omphalocele is generally re- were fathered by her present partner (also noncongarded as an uncommon and sporadic malformation sanguineous). Her first pregnancy was complicated by [Baird and MacDonald, 1981; Czeizel and Vitez, 1981; preterm labor and precipitous delivery at 25 weeks of Hirata et al., 19901,and recurrence risk is reported to be gestation. The 680 g infant female had a nonsyndromal omphalocele,and died on day 1prematurity. During the second pregnancy the patient was sent to our institution for early evaluation. Ultrasound examination at 14 weeks of gestation demonstrated an isolated large Received for publication December 16,1991;revision received omphalocele (Fig. 3). Early amniocentesis was perApril 20, 1992. formed, and the karyotype was 46,XX. At 16 weeks of Address reprint request to Peter G. Ryde, M.D., Division of gestation a spontaneous abortion occurred. The third Reproductive Genetics, Department of Obstetrics/Gynecology, pregnancy was marked by a late presentation for prenaHutzel HospitaINayne State University, 4707 St. Antoine Boulevard, Detroit, MI 48021. tal care. At 29 weeks gestation the patient went into 0 1992 Wiley-Liss, Inc.
Familial Omphalocele
625
TABLE I. Previously Reported Cases of Familial Omphalocele Reference %cot and Gelle [1936] Benson et al. [1949] McKeown et al. [1952] Rothenberg and Barnett 119571 Yuzepe and Johnson [1968] Rott and Truckenbrodt [1974] Osuna and Lindham [1976] Havalad et al. [1979] DiLiberti [1982] Kucera and Goetz [19711 Czeizel [19791 Kapur et al. [1980] Lowry and Baird [1982] Lurie and Ilyina [1984] Lurie (cont) Lurie (cont) Steele and Nevin [1985]
Case #
No. affected
8
3 2 3 2 2 2 3” 4
9 10 11 12 13 14
4 2 2 2 2
15
2“
1 2 3 4 5 6 7
Vertical transmission No No Yes No No No Yes Yes Yes No Yes Yes No No Yes Yes Yes
Other anomalies Encephalocele (113) None None None MZ Twins None None Small VSD W 4 ) None Multiple defects (214) None None None Spina bifida (1/2) Multiple defects (1/2) Multiple defects (1/3) None
2b
16 3* 17 7 a One additional infant with omphalocele excluded due to diagnosis of trisomy 21. Three previous generations each with a member having large umbilical hernias requiring surgical repair (two of whom also had other ventral wall defects as well). ‘Father of affected infants had large inguinal hernia repaired in childhood, and a ventral wall hernia repaired as a n adult. Several maternal relatives required childhood surgery for large umbilical hernias.
labor. After failed tocolysis a classical cesarean section was performed due to breech presentation. The 1,500 g infant boy was found t o have an isolated omphalocele which was repaired. However, after an unstable neonatal period he died a t age 5 months. During pregnancy 4, the patient again presented in premature labor. She failed tocolysis and was delivered, at 30 weeks of gestation, by repeat cesarean section. The 1,590 g male infant had a large omphalocelewhich was repaired, but he died several days later of complications related to prematurity.
MacDonald, 1981; Czeizel and Vitez, 19811. Excluding cases affected by multiple malformations (60-70%) [Benacerrafe et al., 1990; Gilbert and Nicolaides, 19871 and/or chromosome anomalies (4044%) [Gilbert and Nicolaides, 1987; Hughes et al., 19891, the incidence of isolated omphalocelecan be estimated to be on the order of 0.5/10,000. Because even these selected cases are generally regarded as sporadic, recurrence risks are typically counselled to be negligible. Our case, and several previously documented cases suggest that nonsyndroma1 omphalocele is in fact heterogeneous and in some families recurrence risks may be as high as 50%. DISCUSSION The reported cases of familial omphalocele (excluding Large population-based registries have demonstrated syndromal cases such as Beckwith-Wiedemann synthat omphalocele is typically a sporadic congenital drome) are summarized in Table I. Several trends inianomaly affecting 1to 2 in 10,000 live-births [Baird and tially suggested by DiLiberti [19821 are evident. First, in contrast to the entire group of fetuses affected by omphalocele,the familial cases have a lower incidence of associated chromosomal or structural anomalies. In the ........ ........ ........ ........ ........ ........ ........ ........
..... ....... ........ ........ ........ .......
0-0
I
......
I1 2
1
3
Fig. 1. Ultrasound performed at 24 weeks of gestation during fifth pregnancy demonstrating fetal omphalocele. Note midline abdominal defect with clear visualization of membrane surrounding extruded abdominal contents.
5
3
4
6
Fig. 2. Pedigree: W 0 ,omphalocele; 00,family members known to have had “large umbilical hernias” requiring repair in infancy; 0 0 , family members about whom status regarding ventral wall hernias is unknown.
626
Pryde et al.
mechanisms or in some cases chance alone might be operating. Our patient had all 5 of her progeny affected with isolated omphalocele. Although she had no previous family history of true omphalocele there were first and second degree relatives with large umbilical hernias. Previous authors [DiLiberti, 1982; Lurie and Ilyina, 19843have noted the occurrence of umbilical, inguinal, and ventral wall hernias in “unaffected” relatives in families in which omphalocele appeared to be transmitted in a vertical fashion. DiLiberty [19821postulated an autosomal dominant primary defect in abdominal wall structure. He suggested that omphalocele represented the full expression of the defect, while abdominal wall hernias represented affected individuals having a milder expression of the same primary defect. On the other hand, Hinrichsen [19901has emphasized distinct pathogenetic mechanisms, particularly in timing, in the development of true omphaloceleversus umbilical hernia. According t o his model omphalocele is caused by failure of closure of the lateral ectomesodermic folds occurring between 3 and 4 weeks of gestation, in contrast to umbilical hernia which is a true hernia through a defect in the umbilical ring occurring between 8 and 10 weeks of gestation. This model might suggest that those families having members in multiple generations seemingly affected with “omphalocele”in some cases, and “umbilical hernia” in others, may in fact represent cases of “familial umbilical hernia” in which the most extremely affected individuals have umbilical hernias of such a severity that they are neonatally indistinguishable from omphalocele. With present data and diagnostic limitations it is not possible to determine with certainty the genetic cause of Fig. 3. Ultrasound at 14 weeks gestation during second pregnancy. omphalocele in the familial cases reviewed. OmDespite poorer resolution afforded by equipment available at the time, a large midline ventral wall defect (marked by calipers) is imaged on phalocele as a whole does appear to be sporadic in occurthis transverse view at the level of the fetal umbilicus. Fetal spine can rence. However, there can be little doubt that in many of be seen on the left of the figure for orientation. the reported familial cases there is an important genetic contribution. In our case, the finding of umbilical her52 affected fetuses accumulated to date (5 from our case, nias requiring repair in the patient’s brother and his son plus 47 from the 17 families previously reported) there makes an autosomal dominant mechanism with variwere 7 fetuses (13.5%) affected by other anomalies able expressivity a tenable explanation. The collected [Havalad et al., 1979; Kucera and Goetz, 1971; Lurie instances of familial nonsyndromal omphalocele emand Ilyina, 1984; Pucot and Gelle, 19361.While this is a phasize genetic heterogeneity in its cause, and must be substantial increase in structural anomalies over the 3 considered when counselling recurrence risks. to 4% rate which would be expected in the general population, it is much less than the 60 to 70% rate reported in REFERENCES the omphalocele group as a whole. Baird PA, MacDonald EC (1981):An epidemiologic study of congenital Also observed is a tendency in familial cases for a malformations of the anterior abdominal wall in more than half a vertical mode of transmission. In the 17 previously remillion consecutive live births. Am J Hum Genet 33:470-478. ported families, 9 had omphalocele-affectedrelatives in Benacerraf BR, Saltzman DH, Estroff JA, Frigoletto FD Jr (1990): Abnormal karyotype of fetuses with omphalocele: Prediction based more than one generation [Czeizel, 1979; DiLiberti, on omphalocele contents. Obstet Gynecol 75:317-319. 1982;Havaladet al., 1979;Kapur et al., 1971;Lurie and Benson CD, Penberthy GC, Hill J (1949): Hernia into the umbilical cord Ilyina, 1984; McKeown et al., 1952; Osuna and Linand omphalocele in the newborn. Arch Surg 58:833-847. dham, 19761. In one of these 9 families only males were affected, and there were no instances of transmission of Czeizel A (1979): Recurrence risk of omphalocele. Lancet 2:470. A, Vitez M (1981): Etiologic study of omphalocele. Hum Genet the trait by affected males suggesting X-linked inheri- Czeizel 58390-395. tance [Havalad et al., 19791.In the remaining 8 families, DiLiberti J H (1982):Familial omphalocele: Analysis of risk factors and pedigrees suggested autosomal dominant inheritance. case report. Am J Med Genet 13:263-268. The families affected in a single generation (8 of the Gilbert WM, Nicolaides KH (1987): Fetal omphalocele: Associatedmalformations and chromosomal defects. Obstet Gynecol70:633-635. published i 7 families) might represent cases of autosoma1 recessive inheritance, although multifactorial Havalad S, Noblett H, Speidel BD (1979): familial occurrence of
Familial Omphalocele omphalocele suggesting sex-linked inheritance. Arch Dis Child 54:142- 151. Hinrichsen KV (1990): “Human Embryologie.” New York; SpringerVerlag, p 145. Hirata GI, Medearis AL, Platt LD (1990):Fetal abdominal abnormalities associated with genetic syndromes. Clin Perinat 17:675-702. Huges MD, Nyberg DA, Mack LA, Pretorious DH (1989): Fetal omphalocele: Prenatal ultrasound detection of concurrent anomalies and other predictors of outcome. Radiology 173:371-376. Kapur S, Higgins JV, Scott-Emuakpor AB, Dolanski EA (1971): Omphalocele in half-siblings. Clin Genet 1358-60. Kucera J, Goetz P (1971):Exomphalos in four consecutive pregnancies. Hum Genet 13:58-60. Lowry RB, Baird PA (1982): Familial gastroschisis and omphalocele. Am J Hum Genet 3 4 5 1 7 4 1 8 . Lurie IW, Ilyina HG (1984): Familial omphalocele and recurrence risks. Am J Med Genet 17541-543.
627
McKeown T, MacMahon B Record RG (1952): An investigation of 69 cases of exomphalos. Am J Hum Gen 5:168-173. Osuna A, Lindham S (1976):Four cases of omphalocele in two generations of the same family. Clin Genet 9:354-356. Pucot H, Gelle P (1936): Hernie ombilicale embryonnaire recidivante chez 3 foetus successifs. Bull SOC Obstet Gynecol 25296-297. Rothenberg RE, Barnett (1957): Omphalocele in siblings. Arch Surg 75:131-134. Rott HD, Truckenbrodt H (1974): Familial occurrence of omphalocele. Humangenetik 24:259-260. Steele K, Nevin NC (1985): Familial omphalocele. Ulster Med J 54: 214-215. Yuzepe A, Johnson HD (1968): Omphalocele affecting both members of a twin pregnancy. Can Med Assoc J 99:374-376.
