A healthy 33-year-old gravida 4 para 1–1 woman, conceived her fourth pregnancy through in vitro fertilisation. She was in a consanguineous relationship with a second cousin and had no significant family. She had previously experienced a fetal death in utero at 35 weeks gestation secondary to acute parvovirus infection. She had never smoked, consumed alcohol, or used illicit substances. She had no known hazardous environmental exposures. This current pregnancy was high risk for aneuploidy on combined first trimester screening (Trisomy 13:112, Trisomy 18 1:50, Trisomy 21 1:142, nuchal translucency 3.7mm, Free βHCG 1.34 MoM, PAPP-A 1.98 MoM, PLGF 1.12 MoM). Maternal serum testing for cystic fibrosis, toxoplasmosis, rubella, cytomegalovirus, and herpes simplex viruses were negative. The patient initially declined further invasive and non-invasive prenatal testing as she intended to continue the pregnancy regardless of any findings. She opted for serial image-based monitoring.
Fortnightly fetal anatomy ultrasound scans from 20 to 24 weeks gestation demonstrated non-progressive moderate small bowel dilation (7-12mm) and echogenicity within the bowel tissue consistent with a blockage in the distal small bowel (Fig. 1). Amniotic fluid index (AFI), fetal doppler measurements, and fetal movements remained reassuring and within normal limits throughout. At 26 weeks gestation, there was an acute reduction in small bowel dilation to less than 3mm, an increase in echo-free intra-abdominal fluid, and reduced peristalsis on obstetric ultrasound (Fig. 1). Subsequent fetal magnetic resonance imaging (MRI) confirmed a moderate volume of ascites coupled with decreased small bowel dilation (Fig. 2). This was suggestive of a bowel perforation, stenosis, and/or atresia of the proximal ascending colon. Mild cerebral ventricle asymmetry was simultaneously noted with no significant ventriculomegaly. Between 28 to 31 weeks gestation, absent peristalsis and a gradual increase in echo-free ascites with free loops of small bowel in the intra-abdominal fluid were observed on serial ultrasound scans (Fig. 3).
Postulated underlying aetiologies (including metabolic disorders, infection, rare chromosomal pathologies), management options, and prognoses were routinely and extensively discussed with the patient in a multidisciplinary environment. Genetic counsellors noted the unusual anatomical features and hypothesised an underlying metabolic storage disorder such as Niemann-Pick disease or trisomy 21 with erythroblastic component which could only be confirmed postpartum. Paediatric surgeons deemed intrauterine scope and surgery unnecessarily risky in the setting of uncertain aetiology and recommended postnatal surgical review. Frank discussion about unforeseen stillbirth was had the with patient.
Amniocentesis and prenatal array studies at 32 weeks gestation, following fetal corticosteroid coverage, were performed: no abnormalities or infections were detected. At 33 weeks gestation, the mother developed acute symptomatic polyhydramnios characterised by dyspnoea and generalised abdominal pain. There was a simultaneous increase in fetal ascites raising suspicion for mirror syndrome. Amniodrainage of 1400ml of fluid reduced AFI from 35cm to 27cm and was sent for DNA storage testing. The antenatal course was further complicated at 34 weeks gestation by pregnancy-induced hypothyroidism and obstetric cholestasis. The mother was admitted for monitoring, serial bloods, daily ursodeoxycholic acid, and twice daily cardiotocography. Delivery via caesarean section was scheduled for 36 weeks gestation in coordination with obstetricians, anaesthetists, neonatal intensivists, and paediatric surgeons.
An uncomplicated caesarean section for pathological cardiotocography following preterm labour was performed at 35 + 3 weeks gestation. A live 3600g female infant with Apgar scores of 3, 7, and 9 at 1, 5, and 10 minutes of age was delivered and admitted to the neonatal intensive care unit. The newborn had absent bowel sounds, abdominal distention secondary to 500ml of ascites, and severe mid-to-distal gastrointestinal atresia. At three days old, she received a stoma with total parenteral nutrition. She was not suitable for small bowel transplant due to profound combined immunocompromise. The infant received palliative care and succumbed to rhinovirus infection at 8 months of age.
Next generation whole-exome sequencing of neonatal DNA on the Illumina NextSeq Sequencing System uncovered a homozygous pathogenic variant of the TTC7A gene on chromosome 2p21 (OMIM 609332; c.1404delG). This causes an autosomal recessive immunodeficiency syndrome with gastrointestinal defects. Our case is the fifty-third to ever be formally reported worldwide.