Limb body wall complex (LBWC) is a rare and severe syndrome of

congenital malformation A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...

s involving craniofacial and abdominal anomalies. LBWC emerges during early

fetal development Prenatal development () involves the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal deve ...

and is fatal. The cause of LBWC is unknown.

Diagnosis and classification

Traditionally, LBWC is diagnosed by the presence of at least two of the three Van Allen criteria: #

Exencephaly Exencephaly is a type of cephalic disorder wherein the brain is located outside of the skull. This condition is usually found in embryos as an early stage of anencephaly. As an exencephalic pregnancy progresses, the neural tissue gradually degenera ...

encephalocele Encephalocele is a neural tube defect characterized by sac-like protrusions of the brain and the Biological membrane, membranes that cover it through openings in the human skull, skull. These defects are caused by failure of the neural tube to cl ...

with facial clefts #

Abdominal wall defect Abdominal wall defects are a type of congenital defect that allows the stomach, the intestines, or other organs to protrude through an unusual opening that forms on the abdomen. During the development of the fetus, many unexpected changes occur in ...

s: thoracoschisis and/or abdominoschisis # Limb defects As a component of the abdominal wall defect, the umbilical cord is shortened or absent with the fetus being directly attached to the placenta, a key feature in its prenatal diagnosis by ultrasound. Several systems have been proposed to classify LBWC cases phenotypically. Russo et al. (1993) proposed two types distinguished by the presence or absence of craniofacial defects. Sahinoglu et al. (2007) proposed three types based on the anatomical location of defects: * Type 1: Craniofacial defect and intact thoracoabdominal wall; rarely, placenta or umbilical cord attachment to cranial structures * Type 2: Supraumbilical thoracoabdominal wall defect with abdominal organ eventration into the

amniotic sac The amniotic sac, also called the bag of waters or the membranes, is the sac in which the embryo and later fetus develops in amniotes. It is a thin but tough transparent pair of biological membrane, membranes that hold a developing embryo (and l ...

; defective umbilical cord * Type 3: Infraumbilical abdominal wall defect with broad placenta attachment and abdominal organ eventration into the

gestational sac The gestational sac is the large cavity of fluid surrounding the embryo. During early embryogenesis, it consists of the extraembryonic coelom, also called the chorionic cavity. The gestational sac is normally contained within the uterus. It is the ...

; malformed or absent

cloacal A cloaca ( ), : cloacae ( or ), or vent, is the rear orifice that serves as the only opening for the digestive (rectum), reproductive, and urinary tracts (if present) of many vertebrate animals. All amphibians, reptiles, birds, cartilaginou ...

structures In all types of LBWC, some of the fetus's organs develop outside of its body, and the placenta will adhere to the affected body structure (cranium, thorax, or abdomen). The

umbilical cord In Placentalia, placental mammals, the umbilical cord (also called the navel string, birth cord or ''funiculus umbilicalis'') is a conduit between the developing embryo or fetus and the placenta. During prenatal development, the umbilical cord i ...

is significantly shortened. As a consequence, the developing spine and limbs are contorted, leading to

scoliosis Scoliosis (: scolioses) is a condition in which a person's Vertebral column, spine has an irregular curve in the coronal plane. The curve is usually S- or C-shaped over three dimensions. In some, the degree of curve is stable, while in others ...

and limb defects. LBWC can be diagnosed by

prenatal ultrasound Obstetric ultrasonography, or prenatal ultrasound, is the use of medical ultrasonography in pregnancy, in which sound waves are used to create real-time visual images of the developing embryo or fetus in the uterus (womb). The procedure is a stand ...

as early as gestational week 11. Elevated

alpha-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome ...

levels in maternal serum may suggest the possibility of LBWC or another anomaly, motivating ultrasound follow-up. Due to LBWC's extremely poor prognosis, termination of the pregnancy is typically recommended.

Prevalence

LBWC is estimated to occur in 1 in 15,000 pregnancies, with the majority of cases ending in intrauterine death. Its incidence at birth is estimated to be 0.32 in 100,000. Infants with LBWC which survive to term die during or shortly after birth.

Causes

The etiology of LBWC is unknown. Several hypotheses have been proposed: defective

blastodisc The blastodisc, also called the germinal disc, is the embryo-forming part on the yolk of the egg of an animal that undergoes discoidal meroblastic cleavage. Discoidal cleavage occurs in those animals with a large proportion of yolk in their eggs ...

development, vascular disruption during early embryonic development, and early

amniotic membrane The amnion (: amnions or amnia) is a membrane that closely covers human and various other embryos when they first form. It fills with amniotic fluid, which causes the amnion to expand and become the amniotic sac that provides a protective en ...

rupture resulting in mechanical damage to the fetus. Case reports have reported associations between LBWC and placental

trisomy 16 Trisomy 16 is a chromosomal abnormality in which there are 3 copies of chromosome 16 (human), chromosome 16 rather than two. It is the most common autosomal trisomy leading to miscarriage, and the second most common chromosomal cause (closely foll ...

, maternal

uniparental disomy Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or of part of a chromosome, from one parent and no copy from the other. UPD can be the result of heterodisomy, in which a pair of non-identical chromosomes are inhe ...

16,

mosaic A mosaic () is a pattern or image made of small regular or irregular pieces of colored stone, glass or ceramic, held in place by plaster/Mortar (masonry), mortar, and covering a surface. Mosaics are often used as floor and wall decoration, and ...

trisomy 13 A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two. A trisomy is a type of aneuploidy (an abnormal number of chromosomes). Description and causes Most organisms that reprod ...

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

usage, and continued use of

oral contraceptives Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control. The introduction of the birth control pill ("the Pill") in 1960 revolutionized the options for contraception, ...

during early gestation.

References

Congenital disorders of musculoskeletal system Rare diseases Embryology {{Musculoskeletal-stub