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Limb Body Wall Complex - case presentation and literature review

Article in Romanian Journal of Legal Medicine · June 2009

DOI: 10.4323/rjlm.2009.133

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Limb Body Wall Complex - A Case presentation and review of literature

Demetra Socolov1*, Cristina Terinte2*, Vlad Gorduza1*, Razvan Socolov1*, Maria Puiu3§ Address: 1- University of Medicine and Pharmacy Gr. T. Popa, 16 Universitatii Street, Iasi- Romania 2- Hospital of Obstetrics and Gynecology Cuza Voda, Pathology Dept., 34 Cuza Voda street, Iasi- Romania 3- University of Medicine and Pharmacy Victor Babes, Piata E. Murgu 2, Timisoara- Romania *These authors contributed equally to this work

§ Corresponding author

Email addresses: DS: socolov@hotmail.com CT: cterinte@gmail.com VG: vgord@mail.com RS: razvan.socolov@yahoo.com MP: maria_puiu@umft.ro

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Abstract

Background Limb Body Wall Complex (LBWC) is a combination of development abnormalities involving the neural tube, body wall and the limbs. There are few cases in literature, and

• ur case is only the 2nd presented from Romania.

Case presentation The patient was a 31 year-old women G1P0A0 with a 33 week pregnancy which had no prenatal care. The ultrasound scan described several abnormalities, including: large abdominal wall defect, with difficult to identify pelvic organs and ambiguous genitalia; enlarged stomach with suspicion of intestinal atresia; scoliosis and spida bifida occulta with bilateral ventriculomegalia; one inferior limb absent; short umbilical cord with single artery. After therapeutic termination of pregnancy, the abnormalities were confirmed and polycystic liver and kidneys were also mentioned. Also bilateral cardiac ventriculomegalia, left superior pulmonary lobe hemorrhage, imperforated anus and pancreas agenesia were identified. No abnormalities were found at chromosomal examination - 46,XY. Conclusion The case presented here is a placento-caudal phenotype of a LBWC syndrome, which had as a special element the polycystic kidney and hepatic disease. The description of plurimalformative features in our case is important to better understanding of pathogenesis of disease.

Background

Limb Body Wall Complex (LBWC) is a fetal malformative syndrome which consists of neural tub defects, body wall disruption and limb abnormalities. The diagnosis is confirmed by presence of at least two of the above features. The authors report a case of LBWC diagnosed in the late antenatal period. It is the 2-nd case recorded in Romania [1]. The particularity of this case consists in the association of the LBWC malformations with the polycystic disease of the liver and kidneys, not reported before, to our knowledge.

Case presentation

A 31 year-old woman was referred for a 3-rd level antenatal ultrasnography because of a plurimalformative syndrome. She was G1P0A0 at the time of scanning. Her history showed no consanguineous marriage, as well as no toxic or chronic medication exposure. She was not followed-up during the pregnancy before the 33-rd week of gestation, living abroad without health insurance. The TORCH analysis was negative. The first ultrasound scan was performed at 34 weeks, when multiple abnormalities were

• detected. The ultrasound report showed a fetus with a chronological gestational age of 33

weeks (based on the last menstrual period) and an estimate gestational age based on biometry of 36 weeks and 5 days (using BPD, HC, FL). The scan also revealed a large abdominal wall defect through which the abdominal contents herniated into the extra

3 embryonic celom. The protruded organs formed a complex with bizarre appearing and entangled with membranes. The diaphragm was intact. There was evidence that suggest bowel atresia, with a large and dilated stomach. The kidneys and the urinary bladder were not seen, suggesting a renal agenesia, not confirmed by the autopsy. The external genitalia was ambiguous and the pelvic organs were unrecognizable. There was evidence

• f scoliosis and spina bifida occulta with direct signs (incomplete vertebral arches) and

indirect signs (a 14.6 mm cerebral ventriculomegalia, involving the both lateral ventricles, with the cerebellum compressed against the occipital bone – “the banana sign”). While the fetal head diameter was greater than the gestational age, the thoracic and abdominal diameters were reduced. No anomalies were seen at the fetal eyes, facial profile, palate, lips, neck. The cardiac examination was difficult, suggesting an AV channel (with DSV, DSA and single AV valve) which was not confirmed at the necropsy. The superior limbs were normal. The inferior left limb presented club foot, while the right inferior limb was completely absent. The placenta was fundal, showing a 2-nd degree of maturation (Granum classification). The color flow doppler showed evidence of a single umbilical artery with a short umbilical cord, and it also clearly designated the abdominal feto-placental attachment. A provisional diagnosis of LBWC was made based on the ultrasound description. The patient was informed of the poor prognosis and after counselling she accepted the termination of the pregnancy. This was performed with prostaglandin intracervical induction (200 mg x 3 doses, at 4 hour interval). At 23 hours from the onset of the procedure, the patient delivered a still-born fetus of 3000 g. The necropsy report confirmed the diagnosis of LBWC. The anatomical examination of the fetus revealed many pathologic features. The abdominal content herniates by a large abdominal wall defect, with exteriorization of the liver, small and large bowel content, kidneys, and stomach. The examination of lungs indicated a left superior lobe

• hemorrhage. The cardiac examination attested a bilateral cardiac ventriculomegalia and

arterial duct persistence. The necropsy revealed also many cysts (the adult form) in liver and kidneys. One kidney was enlarged (4/6 cm), with a large pielon situated at its inferior pole; the other one was small - 0.4 cm, localized on the surface of the big kidney. The large bowel ended in a “cul-de-sac” manner, into a 3/4 cm pool with thick wall: the

• cloaca. Also, were identified: pancreas agenesia, ambiguous external genital organs,

imperforated anus, lombar neural tube defect (spina bifida occulta) and a stomach with accentuated folds. The microscopical examination of the liver described inflammatory stasis and multiple cysts (0.5-0.8 cm) with serosangvinolent content. In the kidneys we identified many cysts

• f 0.8/1/1.5 cm, disposed in the cortex as in the medullar area of the organ, separated by a

fibrous tissue. The cloaca had a thick fibromuscular wall covered with a squamous epithelium, without keratinisation and urothelium. The umbilical cord was short (17 cm), with two vessels (one artery and one vein separated by a segment of 2 cm). The placenta had important calcifications, thrombosis and capillary congestion. The karyotype effectuated from the cord blood immediately after delivery was normal – 46,XY.

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Literature review and case discussion

Limb body wall complex (LBWC) is a rare, polimalformative fetal syndrome, appearing in 0.21-0.31/10.000 deliveries, with only about 245 cases described in the literature until now [2-5]. Van Allen, who described the syndrome for the first time in 1987, identified 3 essential features: exencephaly/ encephalocele with facial clefts, toraco- and abdominoschisis and limb defect [6-7]. In general, the diagnosis is based on 2 of the above features. Lately, Russo [2, 8] Cusi [3] and Deruelle [13] described two different phenotypes, according to the placental attachment: placento-cranial and placento-caudal type (placento-abdominal adhesion phenotypes). The first phenotype shows craniofacial defects and amniotic bands and/or adhesion; it seems to be related to early vascular

• disruption. The second is without craniofacial defects, but presents urogenital anomalies,

anal atresia, short umbilical cord, abdominal placental attachment and persistence of an extraembrionic celom. Our case can be included in the second phenotype. Kurosawa [5], using the Van Allen criteria for the definition of LBWC, didn’t find any correlation with a certain gender or with the parent’s age. In the literature are not the information about hereditary prevalence, teratogenic agents involved or recurrence risk. The karyotype was always normal, as in our study [6, 7, 9, 10]. Serum alpha-fetoprotein measurement and ultrasonographic examination are the key of prenatal diagnosis. An extremely elevated level of serum alpha-fetoprotein is characteristic to disease. The ultrasound milestone of LBWC consists of thoracic and abdominoschisis, neural tube abnormalities, severe scoliosis, positional deformities and abnormalities of fetal membranes. In our case report we highlight the ultrasound and colour Doppler flow findings in LBWC, demonstrated on routine antenatal scanning, along with the skeletal X-rays and photographs of the still-born fetus and images of microscopic aspects. The pathogenesis of LBWC is unclear. Three pathogenic mechanisms are proposed to be involved: the early amnion rupture theory, the vascular disruption theory and the embryonic dysgenesis. The early amnion rupture theory, proposed by Torpin in 1965 [11], suggests that there is a primary discontinuity of the amnios, inducing the formation

• f amniotic brides, which through a traumatic mechanism produces the amputations of

the limbs. The vascular disruption theory was proposed by Van Allen and hypotheses the embryonic vessel infarctization between the 4-th and 6-th week of gestation, leading to: tissue losses, interruptions in the development of embryonic structures and appearance of amniotic brides. The embryonic dysgenesis theory of Hartwig [12] suggested an anomaly

• f embryonic development, with abnormal caudal and lateral folding, with the persistence
• f the extraembrionic celome, with cord anomaly, placenta and membranes anomalies.

Some consider the LBWC to represent a severe form of amniotic band syndrome, also because the presence of amniotic bands can be highlighted in 40% of the cases with LBWC [9]. In our case no such finding could be demonstrated. The disease is invariably fatal and therefore LBWC needs an early antenatal diagnosis. Van Allen [6], in a review of series of fetuses with LBWC, found: limb defects (95% of cases), spinal abnormalities, ranging from scoliosis (usually severe) to spinal dysraphic defects (in 77% of cases), internal organ malformations (95% of cases) with cardiac defects, absent diaphragm, bowel atresia, renal agenesia or dysplasia. The umbilical cord is usually short, with a single umbilical artery, adherent to the placental membranes.

5 Patten [10] reported trunk defects in 92% of 13 fetuses with LBWC. The involvement of both abdomen and thorax was a more common feature than the involvement of either abdomen or thorax solely. LBWC must be differentiated from abdominal wall defects classified according to their localization: gastroschisis, localized in the paraumbilical area; omphalocele, localized in the umbilical area; ectopia cordis localized at the anterior face of the thorax; amniotic band syndrome; cloacal dystrophy localized at the lower abdominal wall; urachal cyst, localized also at the lower anterior abdominal wall. The diagnosis in LBWC is sustained by some specific signs: the presence of membranes covering the contents of the herniated sac, the association with bowel abnormalities, the presence or absence of urinary bladder and the scoliosis and limb defects.

Conclusion

LBWC is a rare polimalformative syndrome possible to detect at an antenatal ultrasound

• examination. It can be divided in two phenotypes: placento-cranial, due to amniotic bands

syndrome and placento-caudal, due to body stalk syndrome (short umbilical cord). The syndrome is invariably fatal, but the couple must be reassured that there is no risk for recurrence.

Competing interests

The authors declare that they have no competing interests.

Authors contribution

All authors had equivalent contribution to this article.

List of abbreviations

LBWC- Limb Body Wall Complex BPD- biparietal diameter HC- head circumference FL- femoral length

References

• 1. Vladareanu R, Verduta A, Parvu I, Zvarca M, Boruga N. Limb body wall

complex (LBW) at 32 weeks of gestation: case report. Ultrasound in Obstetrics & Gynecology, 2006, 28:534

• 2. Russo R, Vecchione R. Limb body wall complex: craniofacial defects as a

distinctive factor. Birth Defects Orig Artic Ser. 1996, 30(1):157-64.

• 3. Cusi V, Torrents M, Vila J, Antich J, Carrera JM. Limb body wall complex:

analysis of eight fetuses. Birth Defects Orig Artic Ser. 1996, 30(1):165-170

• 4. Martínez-Frías ML. Epidemiological characteristics of amniotic band

sequence (ABS) and body wall complex (BWC): are they two different entities? Am J Med Genet. 1997, 73(2):176-179.

• 5. Kurosawa K, Imaizumi K, Masuno M, Kuroki Y. Epidemiology of limb-body

wall complex in Japan. Am J Med Genet. 1994, 51(2):143-146.

• 6. Van Allen MI, Curry C, Gallagher. Limb body wall complex: I. Pathogenesis.

Am J Med Genet. 1987, 28(3):529-548.

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• 7. Van Allen MI, Curry C, Walden CE, Gallagher L, Patten RM. Limb-body wall

complex: II. Limb and spine defects. Am J Med Genet. 1987, 28(3):549-565

• 8. Russo R, D'Armiento M, Angrisani P, Vecchione R. Limb body wall complex: a

critical review and a nosological proposal. Am J Med Genet. 1993, 47(6):893- 900.

• 9. D’Souza J, Indrajit IK, Menon S. Limb Body Wall Complex. MJAFI 2004,

60:77-80

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sonographic diagnosis of a complicated fetal malformation. Am J Roentgenol. 1986, 146(5):1019-24.

• 11. Torpin R. Amniochorionic mesoblast fibrous strings and amniotic bands. Am

J Obstet Gynecol 1965, 91:65-75

• 12. Hartwig NG, Vermeij-Keers C, De Vries HE, Kagie M, Kragt H. Limb body wall

malformation complex: an embryologic etiology? Hum Pathol. 1989, 20:1071- 1077.

• 13. Deruelle P, Hay R, Subtil D, et al. Antenatal diagnosis of limb body wall
• complex. J Gynecol Obstet Biol Reprod 2000, 29:385-391.

Legend of figures

Photo 1. General appearance Photo 2. Macroscopic appearance- polycystic kidney Photo 3. Microscopic appearance of the kidney Photo 4. Macroscopic appearance- polycystic liver Photo 5. Microscopic aspects- cystic wall from the liver Photo 6. Ambiguous genitalia Photo 7. Short umbilical cord with single artery Photo 8. Ultrasound aspect with liver and bowel protrusion through anterior abdominal defect. The heart is inside the thorax (on the right)

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