Clinical Summary

A 31-year-old woman (G8, T3, P1, A3, L4) was referred for fetal diagnostics at BC Women’s Hospital after routine ultrasound studies at mid-gestation (21 weeks, 6 days)  revealed severe hydrocephalus. The brain anomalies were suspected to be primary (query holoprosencephaly) and a poor prognosis rendered by Medical Genetics. The family elected for termination of pregnancy (24 weeks, 1 day gestational age) via intrafetal digoxin injection followed by dilatation and uterine extraction (D&E). 

For the current pregnancy, clinical investigations revealed unremarkable protective serology and blood work. No gestational diabetes screen was performed and the mother denied exposures to alcohol, smoking or illicit drugs. Notably, the parents were first cousins. Pregnancy history was remarkable for three prior spontaneous abortions and a twin gestation in 2022 involving an unaffected female fetus and abnormal male fetus that was diagnosed with ventriculomegaly at 4-months gestation. The parents were told that this male fetus “would not survive”. The etiology of the ventriculomegaly was presumed to be due to either infection or anemia as the mother has been sick with several episodes of fever during the pregnancy. Clinical investigations at that time revealed no evidence of infection, although no genetic investigations were pursued. Macrocephaly of the male fetus necessitated Caesarean section and at the time of birth this fetus was stillborn. The female twin was liveborn and is currently healthy.   

A complete autopsy was performed. Due to the D&E procedure, the head was not completely intact. Recognizable portions of brain were placed in formalin for fixation.  

Discussion points

1. What are the gross findings?
2. What are the major histological findings?
3. What is the differential diagnosis?
4. What further investigations are warranted to confirm the diagnosis?