Holoprosencephaly (HPE) is a congenital forebrain malformation where the embryonic prosencephalon fails to divide into two separate hemispheres. The result is a single midline cerebral structure (monoventricle) often with craniofacial midline defects.
HPE links early embryology to classic exam clues. Severe facial defects (cyclopia, proboscis) imply alobar HPE, while subtle signs (single maxillary incisor) hint at a microform. It is often associated with trisomy 13 (Patau syndrome) and SHH pathway mutations, so recognition prompts genetic evaluation.
Prenatal US: single large brain ventricle and fused hemispheres, absent interhemispheric fissure.
Child (mild): isolated facial findings (single central incisor, hypotelorism) with learning delays.
MRI: fused cerebral hemispheres with absent corpus callosum; a single ventricle is seen.
Genetics: karyotype/microarray often shows trisomy 13; test for SHH, ZIC2, SIX3 mutations.
If HPE is suspected on fetal US, confirm with fetal MRI to define severity.
Obtain karyotype/microarray (evaluate for trisomy 13/18) and consider gene panels (SHH, SIX3, etc.).
Postnatal MRI to classify (alobar, semilobar, lobar, MIH).
Evaluate for complications: assess pituitary function (diabetes insipidus, adrenal insufficiency), manage seizures, consult neurosurgery for hydrocephalus if present.
Condition
Distinguishing Feature
Agenesis of corpus callosum
Two separate hemispheres (no fused ventricle) but missing corpus callosum; normal appearance of lateral ventricles.
Septo-optic dysplasia
Optic nerve hypoplasia and absent septum pellucidum; milder midline defect without hemispheric fusion.
Hydranencephaly
Destructive loss of cerebral hemispheres (CSF-filled sac); macrocephaly and no brain tissue, differing from developmental fusion.
HOLO prosencephaly = whole forebrain stays as one (one ventricle).
Sonic Hedgehog (SHH) mutations → HPE (Hedgehog → HPE mnemonic).
13 (Patau) has HPE; recall '1 eye, 3 halves' for cyclopia.
Suspect HPE if facial midline defect or abnormal fetal brain ultrasound.
Perform fetal MRI to evaluate brain structure.
Obtain genetic studies (karyotype/microarray for trisomies; HPE gene panel for SHH, SIX3, etc.).
Manage complications: neurosurgical consult for hydrocephalus, endocrine for pituitary issues, and genetic counseling.
Prenatal US: fused thalami + single ventricle → Holoprosencephaly.
Newborn with cyclopia (one eye) and proboscis → Alobar HPE.
Infant with cleft lip and hypotelorism, MRI shows partial hemispheric fusion → Semilobar HPE.
Toddler with a single central incisor and developmental delay → HPE microform.
Case 1
A 22-week fetal ultrasound shows a single large midline ventricle with fused thalami. The fetal face has a small proboscis above where the eyes should be.
Case 2
A 2-year-old has developmental delay and facial anomalies: a single central incisor and cleft palate. Brain MRI is essentially normal with no midline structures missing.
Ultrasound of 14-week fetus with holoprosencephaly: a single midline ventricle (monoventricle) and absent interhemispheric fissure
