VP27.03: Middle interhemispheric variant of holoprosencephaly: prenatal case series and review of literature

The middle interhemispheric variant of holoprosencephaly or syntelencephaly is a prosencephalic cleavage disorder characterised by a deficient interhemispheric separation in the posterior part of the frontal lobe and the parietal lobe. Few cases of accurate diagnosis with prenatal neurosonogram or fetal magnetic resonance imaging have been reported before 20 weeks of gestation. We report on five prenatally diagnosed cases. A search using the databases “PubMed” and- “Trip database” was conducted. Only English-language publications were included. 6 papers published after the year 2000 were retained and reported on 11 prenatally diagnosed cases in total. All 11 cases were diagnosed between 15 and 39 weeks gestational age by prenatal neurosonogram. The cases from this paper were prenatally diagnosed in a tertiary centre over a 5-year period (2012-2017). In this paper, 5 cases with MIH variant diagnosed prenatally between 12 weeks 4 days and 25 weeks 5 days of gestation, are reported. In literature, a ZIC2 mutation was found in 5 out of 11 patients. In our 5 cases, array comparative genomic hybridisation (CGH) and karyotyping was performed. A ZIC2 mutation was found in one patient. In one case a deletion on the long arm of chromosome 10 was detected. All patients opted for termination of pregnancy. Postmortem autopsy confirmed the diagnosis in 9 patients from literature cases and in 3 patients from our cases. Autopsy was not performed in the other two cases because of autolysis or parental refusal. MIH variant of HPE is detectable from the first trimester to early second trimester and should be considered in the differential diagnosis when the cavum septi pellucidi is absent. Fetal Neurosonography and MRI should be performed to distinguish it from other midline brain anomalies. Genetic analysis and autopsy should be conducted to investigate this more recent and rare variant.