Dual intestinal anomalies in dizygotic twins

Abstract

We report on the case of two digestive malformations in dizygotic/dichorionic/diamniotic twins born at 31 weeks of gestation. The mother (gravida 1 para 0) was treated by hydroxychloroquine for systemic lupus erythematosus during pregnancy. Twin A presented an arch-like dilatation on antenatal ultrasounds, characteristic of segmental volvulus. After birth, twin B presented repeated vomiting on feeding, leading us to diagnose ileal atresia despite normal antenatal ultrasounds. Both twins underwent surgery and the postoperative period was uneventful. After 1 year of follow-up, the twins are in excellent health without digestive sequelae. Genetic testing for cystic fibrosis was negative. The placenta showed diffuse signs of hypoxia and ischaemia, indicating that the root cause was vascular. The pathophysiology of intestinal atresia is hypothesised to derive from a vascular incident during fetal development. We are therefore led to believe that an intrauterine vascular event is the most likely cause of the dual malformation.

Background

Our case report describes an uncommon occurrence: two separate digestive malformations in dizygotic/dichorionic/diamniotic twins with no obvious underlying cause.

It is relatively common for digestive anomalies to be diagnosed prenatally. However, it is rare among twins that both are affected by a digestive malformation. As it is exceptionally rare to diagnose one malformation prenatally and the other postnatally, we wish to describe our diagnostic and therapeutic approach. Taking into account the placental histopathology, what is known of intestinal atresia pathophysiology, the patients’ clinical presentation and the mother’s medical history, we are led to believe that the most likely cause of the dual malformation is an intrauterine vascular event. We would like to draw readers’ attention to the fact that a congenital digestive malformation could be present even if prenatal ultrasounds appear normal, and that when confronted with unexplained congenital abnormalities, vascular causes should be investigated.

Case presentation

A 28-year-old woman, gravida 1 para 0, was referred at 26 weeks of gestation of dizygotic/dichorionic/diamniotic twins for suspected intestinal dilatation detected on fetal ultrasound. The mother has a history of systemic lupus erythematosus (SLE) with positive anti-Sjögren’s syndrome type A and anti-Sjögren’s syndrome type B antibodies, treated by corticosteroid therapy and hydroxychloroquine (HCQ). Her past complications include myopericarditis, bilateral pleuritis and macrophage activation syndrome. The first trimester ultrasounds did not detect any abnormalities. At 19 weeks of gestation, twin A’s intestine was hyperechogenic, but twin B’s ultrasound was completely normal. At 20 weeks of gestation, a large arch-like intestinal dilatation of twin A was detected, without any other associated anomalies (figure 1). The fetal ultrasound of twin B remained normal. In light of the ultrasound anomalies, genetic diagnostic testing of the cystic fibrosis transmembrane conductance regulator gene was carried out in both parents, but revealed no mutations. For twin A, the suspected diagnosis was thus segmental volvulus of the small intestine. Antenatal corticosteroid therapy for fetal pulmonary maturation was performed, and the twins were born by spontaneous vaginal delivery prematurely at 31 weeks of gestation due to premature rupture of membranes. The twins adapted well to extrauterine life. Twin A (male) weighed 1600 g (eutrophic) and had a distended abdomen on clinical examination. Twin B (female) weighed 970 g (hypotrophic) and clinical examination was unremarkable.

Figure 1.

Fetal ultrasonography of twin A at 20 weeks of gestation showing the characteristic arch-like intestinal dilatation (arrow) that led to a prenatal diagnosis of segmental intestinal volvulus.

Twin A’s abdominal X-ray at birth showed voluminous distension of the proximal small intestine with possible pneumoperitoneum. Contrast enema showed normal opacification and morphology of the colon, but lack of opacification of the small intestine. Surgery was performed shortly after birth. Laparotomy revealed a perforated segmental volvulus of the jejunum as well as pneumoperitoneum and significant inflammatory adhesions between intestinal loops and widespread bilious effusion (figure 2). Given the extent of the bowel inflammation, an end-jejunostomy was performed after intestinal resection of the volvulated loop. Secondary end-to-end jejunal anastomosis was completed 2 months later. The postoperative period was uneventful, and the patient was discharged at 3 months of age. On a routine urinalysis, an elevated microalbuminuria/creatininuria ratio was detected, and the kidney ultrasound revealed a bilateral nephrocalcinosis. Genetic testing for primitive hyperoxaluria proved negative. A sweat test performed at 6 months of life confirmed the absence of cystic fibrosis.

Figure 2.

Intraoperative image of twin A’s perforated segmental volvulus of the jejunum (arrow) with intestinal inflammatory adhesions.

Unlike twin A, twin B’s antenatal ultrasounds were normal and no signs of intestinal dilatation or stenosis were detected. However, when she began nursing at 12 hours of life, she presented repeated episodes of vomiting and a clinically distended abdomen. Abdominal X-ray and contrast enema at 2 days of life revealed a small intestinal dilatation, a normal colon opacification and an absence of distal ileum opacification. This led us to suspect ileal atresia (figure 3). Laparotomy was performed the following day involving a resection of the stenosis (type I ileal atresia) and end-to-end anastomosis. However, the patient presented a prolonged ileus and distended abdomen during the postoperative period leading to a second exploratory surgery 10 days later and implementation of an ileostomy. Secondary end-to-end ileal anastomosis was completed 6 weeks later. The postoperative period was uneventful, and the patient was discharged at 3 months of life. A sweat test performed at 6 months of life confirmed the absence of cystic fibrosis, and her kidney ultrasounds as well as her urinalysis were completely normal.

Figure 3.

Twin B’s abdominal X-ray (A) showing a diffuse bowel dilatation. Contrast enema (B) showing the normal colon opacification, absence of distal ileum opacification and small intestine dilatation that led to a postnatal diagnosis of ileal atresia.

Macroscopically, twin A’s placenta was unremarkable, and twin B’s placenta was hypotrophic and bilobed. The microscopic pathology of the two fused placentas showed diffuse signs of hypoxia and villous ischaemia corresponding to chorionic villi congestion and hypotrophy as well as widespread clusters of syncytiotrophoblastic nuclei.

Outcome and follow-up

After 1 year of follow-up, twin A and twin B are in excellent health without digestive sequelae. They have a normal oral alimentation and a normal intestinal transit. They present a normal linear growth with an excellent weight gain.

Discussion

Intestinal atresia and intestinal volvulus are two of the most common causes of short bowel syndrome in the paediatric population, along with necrotising enterocolitis.¹ Intestinal volvulus can be either complete or segmental. Complete intestinal volvulus is most often secondary to an underlying intestinal malrotation. Segmental intestinal volvulus is a more rare condition and often secondary to congenital or postoperative bands, duplication cyst, internal herniation and intestinal atresia.^{1 2} Even more rare and difficult to diagnose is prenatal intestinal volvulus, most of which occur without intestinal malrotation. Clinical signs (decreased fetal movement), as well as direct (whirlpool sign, coffee bean sign) and indirect (abdominal mass, dilated bowel loops, pseudocysts, ascites, polyhydramnios) ultrasound signs, are inconsistent and non-discriminative.¹ Likewise, the prenatal diagnosis of intestinal atresia is challenging, and sonographic signs are remarkably similar to those of intestinal volvulus. Although the pathophysiology of intestinal atresia is uncertain, the most commonly accepted hypothesis is a vascular incident in the late stages of embryonic development. This results in a localised ischaemia and scarring of the intestinal tissue, leading to an abnormal development of the enteric nervous system. Long-term prognosis for both of these intestinal malformations is favourable when small bowel length is conserved and surgery is timely performed.³

Our case report describes an uncommon occurrence: two separate digestive malformations in dizygotic/dichorionic/diamniotic twins, with no obvious underlying cause. Our first hypothesis was cystic fibrosis which is known to cause digestive disorders including pancreatic insufficiency, cholelithiasis, intussusception, intestinal volvulus and atresia.⁴ However, this theory was disproved by negative genetic testing of the parents and negative sweat tests of the children.

The mother of the twins has SLE treated by corticosteroid therapy and HCQ. HCQ is able to cross the placenta, and the concentrations of the cord blood are equal to those found in maternal blood.⁵ However, an extensive review of literature shows that no HCQ-induced malformations have ever been reported in humans.⁵ It therefore seems unlikely that HCQ could be a causal factor.

Although no link between SLE and neonatal digestive malformations has been described, SLE is associated with multiple adverse obstetric outcomes. Clowse et al demonstrated that fetuses of SLE mothers are at an increased risk for miscarriage, perinatal mortality, prematurity and low birth weight, especially if an antiphospholipid syndrome is associated.⁶ Our patients’ mother had no prior history of thrombotic complications nor was she positive for antiphospholipid antibodies. However, the microscopic pathology of the two fused placentas showed diffuse signs of hypoxia and villous ischaemia corresponding to chorionic villi congestion and hypotrophy as well as widespread clusters of syncytiotrophoblastic nuclei. Macroscopically, twin A’s placenta was unremarkable and twin B’s placenta was hypotrophic and bilobed. Our primary hypothesis is thus an in-utero vascular incident that caused possibly two digestive malformations: an intestinal volvulus for twin A and an intestinal atresia for twin B. It is possible that both twins initially presented an intestinal atresia and twin A’s malformation was further complicated by a volvulus (intestinal atresia leads to dilatation of the bowel loop that favours segmental intestinal volvulus). We cannot say with certainty that ileal atresia was present intraoperatively because the volvulated loops were necrotic and perforated, making ileal atresia difficult to identify even with careful pathological examination. Our theory of an intrauterine vascular event is further supported by twin B’s low birth weight, as placental vascular pathologies are a leading cause of intrauterine growth restriction.⁷

Conclusion

Intestinal volvulus and intestinal atresia are common causes of short-bowel syndrome in the paediatric population, however their underlying cause is not always understood. Our case reports on a rare occurrence of dizygotic/dichorionic/diamniotic twins each presenting with a digestive malformation with no apparent associated genetic aetiology. Taking into account placental histopathology, what is known of intestinal atresia pathophysiology, the patients’ clinical presentation and the mother’s medical history, we are led to believe that the most likely cause of the dual malformation is an intrauterine vascular event. In conclusion, we suggest that when physicians are confronted with unexplained congenital abnormalities, vascular causes should be investigated.

Learning points.

• A large arch-like intestinal dilatation on a fetal ultrasound is a prenatal sign consistent with a segmental intestinal volvulus.

• When a digestive malformation is diagnosed prenatally in one twin, another digestive malformation could occur in the other twin, even if fetal ultrasounds appear normal.

• Vascular causes should be investigated for unexplained congenital abnormalities.

• Although systemic lupus erythematosus (SLE) is associated with multiple adverse obstetric outcomes (increased risk for miscarriage, perinatal mortality, prematurity and low birth weight), no link between SLE and neonatal digestive malformations has been described.