Prevalence:

• 1 in 1,300 fetuses at 12 weeks’ gestation.
• 1 in 10,000 births.

Ultrasound diagnosis:

• Abnormalities from incomplete cleavage of the forebrain observed in the standard transverse sections of the brain.
• There are 4 types:
  • Alobar: fusion of the cerebral hemispheres with a single ventricle.
  • Semilobar: cerebral hemispheres and lateral ventricles are fused anteriorly but separated posteriorly.
  • Lobar: cerebral hemispheres are separated both anteriorly and posteriorly, but there is partial fusion of the frontal horns of the lateral ventricles, absence of septum pellucidum and abnormalities of the corpus callosum, cavum septum pellucidum and olfactory tract. The main differential diagnosis is septo-optic dysplasia and therefore an attempt should be made to examine optic chiasm and optic nerves by MRI.
  • Syntelencephaly, the anterior and occipital areas of the brain are fully cleaved as in the lobar type, but unlike this, there is no parietal cleavage and therefore the Silvian fissures are vertically oriented and abnormally connected across the midline over the vertex of the brain.
• Lobar holoprosencephaly is detectable at >18 weeks’ gestation, but the other three types can be detected at the 11-13 weeks scan.

Associated abnormalities:

• Chromosomal defects, mainly trisomies 13 or 18, are found in >50% of cases at 12 weeks’ gestation.
• Genetic syndromes are found in 20% of cases.
• Alobar and lobar holoprosencephaly are associated with microcephaly and midfacial defects in 80% of cases. Extracerebral defects are particularly common in fetuses with trisomies 13 and 18 and those with genetic syndromes.

Investigations:

• Detailed ultrasound examination, including neurosonography.
• Invasive testing for karyotyping and array.
• Fetal MRI may be useful for confirmation of diagnosis in cases of suspected lobar holoprosencephaly.

Follow up:

• If pregnancy continues, follow-up should be standard.

Delivery:

• Standard obstetric care and delivery.

Prognosis:

• Alobar and semilobar: usually lethal within the first year of life.
• Lobar: life expectancy may be normal but usually with severe developmental delay and visual impairment.

Recurrence:

• Isolated: 6%.
• Part of trisomies: 1%.
• Part of genetic syndromes: 25-50%.