University of Alabama at Birmingham
Children's Hospital of Alabama; University of Alabama at Birmingham
Holoprosencephaly is a congenital malformation secondary to incomplete cleavage of the prosencephalon during the third week of embryonic development. It can be suspected when a newborn demonstrates midline facial defects of varied degrees. Its etiology is multifactorial, including genetic, teratogenic, or syndromic.
Educational Goals / Teaching Points
Describe embryologic the mechanism of holoprosencephaly. Discuss imaging features of the holoprosencephaly spectrum. Evaluate the distinguishing factors from imaging mimics.
Key Anatomic/Physiologic Issues and Imaging Findings/Techniques
The spectrum of holoprosencephaly (HPE) is assessed with greatest sensitivity with MRI. Prenatal ultrasound allows depiction of the facial and central nervous system abnormalities of severe HPE but is less sensitive than MRI for entities toward the less severe end of the spectrum. The mildest form of the spectrum is Septo-Optic Dysplasia (SOD), in which there is absence of the septum pellucidum. This is seen in conjunction with hypoplasia of the optic nerves, optic chiasm, and pituitary. The cerebral hemispheres are separated and the corpus callosum is present. HPE per se ranges from lobar to alobar (mild to severe), with a common classic characteristic that allows prenatal sonographic diagnosis: a single/azygos anterior cerebral artery that is displaced anteriorly and abuts the skull; thus, named the “snake under the skull” sign. Alobar HPE can be diagnosed prenatally with the absence of “butterfly-like” choroid plexus. MRI shows a single midline forebrain with a “pancake-like” appearance with a primitive monoventricle and often a large dorsal cyst. There is absence of the corpus callosum, interhemispheric fissure, septum pellucidum, and 3rd ventricle. 50% of patients with alobar HPE die by 5-months of age and only 30% survive after 1 year of age. Absence of the cavum septum pellucidum is vital to ensure detection of the milder forms. In semilobar HPE, 50% of the frontal lobes are fused and part of the corpus callosum or third ventricle may be seen. Additionally, the interhemispheric fissure and falx cerebri may be present posteriorly. Even further, patients with lobar HPE may only have fusion of a few frontal gyri and have absence of the septum pellucidum. Their interhemispheric fissure extends across almost the entire midline and the corpus callosum may be normal. Survival of semilobar and lobar HPE is more than 50% after 1 year. Hydranencephaly and severe hydrocephalus are common mimics of HPE. However, there is presence of the septum pellucidum and the falx cerebri in severe hydrocephalus. Also, there is presence of the falx cerebri and absence of cortical tissue in hydranencephaly. Additionally, an interhemispheric cyst related to corpus callosum agenesis can appear similar to the dorsal cyst of HPE.
The diagnosis of HPE can be challenging, particularly in the less severe end of the spectrum. The features of semilobar and lobar HPE as well as SOD should be taken into consideration when evaluating brain imaging of neonates with developmental delays.