2006-05-11-16 OEIS complex © Cuillier www.thefetus.net/
Cuillier F, MD*, Gauvin P, MD**, Alessandri JL***
* Department of Gynecology, ** Radiologist, Saint-Denis, *** Department of Neonatology, Réunion Island, France.
Definition: Omphalocele-Exstrophy-Imperforate anus-Spinal defects (OEIS) are a rare complex. OEIS represents the most severe form of Epispadias-exstrophy sequence ranging from phallic separation with epispadias, pubic diastasis, exstrophy of the bladder (isolated), cloacal exstrophy to OEIS(1-2). Exstrophy of the cloaca is a well-known malformation that includes the persistence and the exstrophy of a cloaca that receives ureters, ileum and a rudimentary hindgut. This anomaly is associated with failure of fusion of the genital tubercles and pubis rami, incomplete development of the lumbo-sacral vertebrae with spinal dysraphism, imperforate anus, cryptorchidism, epispadias, anomalies of mullerian duct in females and urinary tract anomalies. Then OEIS acronym is used (3).
Synonyms: OEIS syndrome, Cloacal dystrophy; Vesicointestinal fissure; Splanchnica exstrophia; Exstrophy-epispadias sequence
Case report: This is a 38-year-old-woman, G5P4, with relevant past history. She was referred to our unit at 24 weeks due to the diagnosis of a spinal defect and a cloacal dystrophy. The triple test and the nuchal translucency were not performed. The ultrasound findings were:
Hyperechoic mass in front of the perineum
Single umbilical artery
Myelomeningocele without skin defect
Normal brain (Arnold Chiari syndrome was excluded)
The bladder was not seen.
Transverse scan of the pelvis at 24 weeks showing a mass between the legs
Transverse view from chest to perineum showing a large anterior wall defect with an echoic mass floating in the amniotic fluid. There is no evidence of bladder.
Transverse view at 24 weeks showing the lumbo-sacral spinal defect
Sagittal view at 24 weeks showing the spinal defect with myelomeningocele over the lower back of the fetus. The skin seems intact.
MRI sagittal and coronal view at 24 weeks
Postnatal view. Note lower abdomen with the midline defect including the exstrophy of the bladder and omphalocele.
Dorsal view. Note imperforate anus. We can not see the neural tube defect because the skin is intact, covering the defect.
The diagnosis of OEIS was suspected. The patient decided to interrupt the pregnancy. An MRI was performed. The interruption was performed at 25 weeks. A non-viable fetus, weighing 450g was delivered. The ultrasound findings were confirmed. The exstrophy of cloaca and omphalocele were visualized. The karyotype was normal (46XX). The parents refused the necropsy.
History: The first description of a case of OEIS was published by Littre in 1709(5). The term of OEIS complex was first used by Carey et al in 1978. He described a congenital syndrome, with multiple malformations (omphalocele, exstrophy of bladder, imperforate anus and spinal defect) (3). Previous terminology was ectopia of cloaca, vesicointestinal fissure or exstrophy splanchna (6). Girz et al (1998) described one case of OEIS diagnosed at 15 weeks. It is actually the earliest scan report of findings associated with OEIS complex (7).
Usually, the OEIS is diagnosed during the second trimester, rarely during the first trimester, essentially because the anomaly of spine is difficult to diagnose and the cloacal exstrophy might not be exteriorized at this moment of the pregnancy.
Prevalence: The fetal OEIS is a defect that affects the midline of the lower inferior body. OEIS occurs with an incidence of 1:250.000 live births. The occurrence of exstrophy of the bladder appears to be more common (1:30 000 to 1:40 000) than exstrophy of cloaca (1:200.000 to 250.000) or OEIS (1:200.000 to 1:400.000) pregnancies (8). The incidence of OEIS is probably higher because many cases are diagnosed incorrectly as omphalocele, which is the most prominent component of this malformation complex (9). A male predominance was observed in the original report by Carey et al (10). Schinzel et al (1979) estimated that 10% of all cases of cloacal exstrophy occur in same sex twins and suggested that multiple pregnancy and early malformations, such as exstrophy are related (3). Karyotype is usually normal, according to Witters (4).
Etiology: OEIS etiology is unknown, but several associations have been suggested:
Teratogenic exposition: diazepam (7-14), diphenylhydantoin (3)
Genetic factors: possibly associated (47 XXX ; T18) (11).
Single defects in blastogenesis and mutations in Homeobox genes (such as HLXB9) have been suggested to be responsible for the development of the OEIS complex. HLXB9 has also been described in association with the Currarino triad (associated sacral agenesis, anal defect including imperforate anus and anal stenosis, presacral teratoma and spinal cord tethering) (3).
Multiple pregnancies: Higher incidence of OEIS in monozygotic twins suggests a possible genetic contribution to the occurrence of this multisystem defect (2). Indeed, Lee et al (1999) describe a case of OEIS complex in monozygotic twins. This concordance of monozygotic twins for the defects may support the theory that early malformation complexes as OEIS and monozygotic twinning are manifestations of the same discordance of early blastogenesis (9)
Sporadic familiar occurrence: the most frequently etiology
Recurrence of omphalocele or bladder exstrophy in sibs has been documented, with a risk of less 1% (5). Only according to Smith (1992), OEIS has been reported in both of a pair of monozygotic twins on two occasions, but recurrence in sibs born in separate pregnancy has not been previously reported before Smith (5).
Pathogenesis: The cloaca constitutes a functional definitive organ in the batrachians, reptiles and birds. Nevertheless in humans, the cloaca is a phylogenetic embryonic structure where the genital, urinary and digestive organs join caudally. The normal development gives origin to the lower abdominal wall with bladder, intestine and anus, genitals organ and part of the pelvis bones and lumbo-sacral spine. So OEIS is considered to be a defect in blastogenesis, beginning in the first four weeks of human development. According to different authors, OEIS has probably a heterogeneous etiology and may result from a single localized defect in early caudal mesoderm at approximatively 29 days of development and it is thought to lead to one of three defects (12):
Failure of cloacal septation: resulting in a common cloaca.
Breakdown of the cloacal membrane: resulting in exstrophy and omphalocele.
Incomplete vertebral fusion: resulting in open neural defect (Spina bifida).
Some authors have suggested to use the terms exstrophy of the cloaca and OEIS as synonyms, since they may be caused by the same event in early blastogenesis. This defect may be responsible for the insufficient development of the uro-rectal septum in addition to differences in the timing and extent of mesenchymal growth.
Sonographic findings: Austin et al described major criteria for the prenatal diagnosis of OEIS (non visualization of the fetal bladder, infra-umbilical abdominal wall defect, omphalocele, myelomeningocele) and minor criteria (lower extremities malformations, renal anomalies, ascites, widened pubic arches, narrow thorax, hydrocephalus, single umbilical artery) (8). According to the literature, sonographic findings of OEIS complex have been documented, but only few cases of prenatal diagnosis have been reported. Nevertheless, nowadays, the prenatal diagnosis of OEIS is possible by the identification of:
A midline infra-umbilical defect with an irregular mass: in the inferior abdominal wall or cystic anterior wall structure (persistent cloacal membrane) or with omphalocele.
Absence of the bladder between the two umbilical arteries.
Lumbo-sacral myelomeningocele: always seen. Common spinal defect include hemivertebrae, sacral anomalies and either tethered cord and meningocystocele. But it is important to known that Kâllen et all wrote that the spinal defect may occur more cranially and are not restricted to the lumbo-sacral region (11).
Anomalies of the inferior limbs are possible but club feet, limb duplication or amputations are generally not seen with OEIS (13).
Wide pubic arch is classically present with symphysis pubis diastasis and congenital hip dislocation.
Single umbilical artery: It is a frequent associated sign (15).
Genital anomalies. Classically, the sex determination is often not possible. Other uro-genital anomalies are possible, including genital duplication.
The majority of authors consider OEIS as a distinct syndrome, but there is a discussion if the exstrophy of the bladder sequence, exstrophy of the cloaca sequence or urorectal septum malformation sequence should be referred to distinct clinical entitities.
Implications for target examinations: OEIS should be considered in patients with an absent bladder associated with an anterior abdominal wall defect or spine defect. Associated anomalies must be searched for other combined anomalies. Color Doppler to identify the umbilical artery is very useful in establishing the diagnosis of OEIS (15). The umbilical artery arises from the internal iliac arteries and run along the urinary bladder before entering the umbilicus. So the color Doppler may be helpful to locate the umbilical artery.
In our case, we found that the single umbilical artery ran along the side of the mass in the lower fetal abdomen. According to the ultrasound findings, we were convinced that the origin of the mass was the exteriorized urinary bladder associated with a small omphalocele. The diagnosis of OEIS seemed confirmed by MRI. Color Doppler is important in that cases of bladder exstrophy, but direct flow of urine (ureteral jets) may be depicted (with difficulties) in direct communication with the amniotic cavity. In our case, because there was an severe oligohydramnios, it was really impossible to visualize the urethral jets.
Differential diagnosis: Differential diagnosis finding includes:
Omphalocele and gastroschisis: An extruded sac or herniate bowel in the amniotic cavity with a normally filled bladder seen in the pelvic cavity is a characteristic finding of these two conditions.
Bladder exstrophy: impossibility to visualize the bladder
Limb-body wall complex (LBWC) : OEIS complex is recognized by an absent bladder, as opposed to LBWC. LBWC is a rare sporadic defect defined by the presence at least two of three characteristics:
- 1. limb defects
- 2.anterior body wall defects
- 3. exencephaly or encephalocele with or without facial clefts. Nevertheless there is significant overlap between OEIS and LBWC (16).
There is two clearly separate phenotypes:
The first phenotype: presents crania-facial defects and amniotic bands and/or adhesion.
The second phenotype: shows uro-genital anomalies, anal atresia, and abdominal placenta attachment with a persistence of the extra-embryonic celoma.
Pentalogy of Cantrell: Spinal defects will be absent and anterior thoracic defect with associated ectopia cordis will be seen. Although omphalocele as well as exstrophy of the bladder may occur in the pentalogy of Cantrell, the characteristics thoracic defects in Cantrell’s pentalogy should facilitate differentiation from the OEIS complex.
Amniotic band sequence
Aneuploidy: can be responsible with OEIS (Trisomy 18). OEIS has been reported in association with the Opitz/BBS syndrome, Goltz syndrome, Occulo-auriculo-vertebral sequence and fronto-nasal dysplasia (3).
Associated anomalies: Different anomalies can be associated with OEIS complex :
Cardiac anomalies: cardiac defects have been described with exstrophy of the cloaca alone (as atrial and ventricular defect). But cardiac defects are described in combination with the OEIS complex in only three reports (13)
Increased nuchal translucency: Only one case associated with OEIS was described by Schem et al (2). The most likely cause of increased nuchal translucency is probably vascular or hemodynamic, but the mechanism remains unclear. Nevertheless, there is no evidence for jugular lymphatic obstruction sequence in OEIS.
Markedly elevated serum levels of alfa fetoprotein: always associated.
But most cases of OEIS complex are diagnosed only at autopsy after interruption of pregnancy.
Prognosis: The prognosis of infants with OEIS complex is variable, depending on the severity of the structural defects. Survival will depend on the extension of the cloacal exstrophy and the neural tube defect. In less severe forms, good outcome with corrective surgery is possible. Cloacal exstrophy is lethal due to obstruction of the urinary tract and association with renal and pulmonary complications. So early prenatal diagnosis of OEIS complex is required to give parents the option to terminate the pregnancy. And it is also helpful to plan the appropriate perinatal management. In cases which parents decided to continue the pregnancy, serial scans are necessary to evaluate the progress of the ventriculomegaly, which can be associated with OEIS. But, we think that cesarean section should be performed in cases of OEIS complex to avoid dystocia and trauma.
Management: It seems essential to perform an early scan in the next pregnancy, because an accurate prenatal diagnosis of OEIS complex associated with malformations, is important for the detailed counseling of the family (interruption of pregnancy) and appropriate perinatal management by the obstetricians, pediatric surgeons, neurosurgeons, neonatologist, but especially anatomic-pathologist.
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