Limb body wall complex – a case series and review of the literature

Abstract

Introduction: Limb body wall complex is defined by the presence of exencephaly and either facial clefts, thoraco- and or abdominoschisis and limb defect. This condition is rare with an incidence of 0.83/1000 in this case series. The aetiology is unknown but two theories best support the evidence. These are firstly that there is early vascular disruption between the 4 and 6 week of gestational age and secondly that there is early amnion rupture sequence in combination with a defective folding process in the embryo [1, 2]. However a similar abnormality has been described in the mouse which is caused by the disorganization gene and there is suggestions for the existence of a human homologue gene [3, 4]. Methods: All abortions or births coded as limb body wall defect or fetal exencephaly between January 1996 to January 2001 were reviewed. Those cases that fulfilled the criteria of limb body wall complex on postmortem examination were summarized. The criteria were: exencephaly [1] or encephalocele [2] facial cleft, thoraco- and/or abdominoschisis [3], limb defect. Results: During the 5-year period, there were 13 286 deliveries. Of these, 11 cases met the criteria of limb body wall complex giving an incidence of 0.83/1000 deliveries. Mean maternal age was 29 (SD 5.9) years, and the mean gravidity and parity were 3 (IQR 2–4.5) and 0 (IQR 0–1.5). In 50% (5/10), 50% (5/10) and 30% (3/10) of women a history of cigarette, alcohol and marijuana use, respectively, was noted. Furthermore, 40% (4/10) of the women had a history of a previous infant with a congenital anomaly being, respectively, amniotic band syndrome, cleft-lip, atrial septal defect and a previous affected pregnancy with LBWC. In this latter case, two male infants with LBWC occurred in one patient, supporting the hypothesis that some cases may be due to an X-linked disorganization gene. Overall, the gender of the affected infant was male. All cases were diagnosed with a major abnormality, usually exencephaly, on ultrasound examination between 15 and 19 weeks gestation. The specific diagnosis of LBWC was usually not made until postmortem examination (91% of cases). One patient had an ultrasound at 17 weeks gestation that was reported as normal, only to have exencephaly subsequently diagnosed on ultrasound at 19 weeks gestation. Without interruption of pregnancy, one fetus survived for 18 h following delivery for its twin at 35 weeks gestational age. Conclusion: Limb body wall complex is a rare fetal anomaly. Structural components of the syndrome, ususally exencephaly, can be identified on second trimester ultrasound examination; however, the definitive diagnosis is usually not made until postmortem examination. Several possible mechanisms for LBWC have been discussed including early amnion rupture sequence in combination with a defective folding process, early vascular disruption and genetic factors. The mouse mutant disorganization is semi dominant with 72% of heterozygotes manifesting abnormalities, which include cranioschisis, gastro/thoracoschisis and limb defects. A human homologue for disorganization may be the cause for at least some examples of LBWC [3, 4]. The predominance of male fetuses suggests that there may be a X-linked inheritance. However, environmental teratogens such as nicotine, alcohol or illicit drug abuse may be responsible to manifest the disorder in other cases by impairing the uteroplacental flow during critical periods of development as shown in mouse and rat fetuses [5-7].