HOLOPROSENCEPHALY

Holoprosencephaly is a spectrum of malformations characterized by incomplete cleavage of the prosencephalon during prenatal cortical development. The brain anomalies of holoprosencephaly are manifested in three patterns: alobar, semilobar, and lobar types. 
1. Alobar: One single ventricle of variable size is present with a dorsal membrane closing the holosphere. The fluid-filled ventricle may bulge against the membrane, forming a ‘dorsal sac.’ The corpus callosum and olfactory tracts and bulbs are absent, while the midline thalami and corpora striata are present. This subtype represents the majority of cases. The condition is usually associated with midline facial anomalies organized into four main categories increasing in severity from cleft lip and palate with ocular hypotelorism, cebocephaly with ocular hypotelorism and a single-nostril nose, ethmocephaly with ocular hypotelorism, and cyclopia (1). 
2. Semilobar: Elementary cerebral lobes are present. A midline posterior fissure separates the hemispheres in some cases. Olfactory bulbs and tracts are either absent or hypoplastic, and a rudimentary corpus callosum is present. Facial anomalies are milder and include cleft lip and palate and hypotelorism.
3. Lobar: Though two hemispheres exist, a midline fissure persists between them. The olfactory tracts, bulbs, thalami, and corpora striata may or may not be complete. Facial anomalies are absent or mild , similar to the semilobar form. 

The prevalence of holoprosencephaly is 1.26: 10,000 deliveries (2). The mean maternal age for holoprosencephalic development is 27 years with detection at 21 weeks, and delivery at 23 weeks of gestation (2). The male:female ratio for cases is 1.4:1.0 (2). 

Holoprosencephaly may result from teratogen exposure or chromosomal abnormalities. Trisomy 13 (Patau’s syndrome) accounts for 40% of cases (4). Trisomy 18 is less frequently associated.


Ultrasound findings:

Lobar Holoprosencephaly:

There is a single midline ventricle (monoventricle), which is horseshoe shaped. The thalami are echogenic and are fused. There is a thin pancake like mantle of undifferentiated cerebral parenchyma.  The frontal, temporal, and occipital horns are not separated.  The monoventricle may become large and herniate superiorly forming a dorsal cyst or sac.  The corpus callosum, falx cerebri, interhemispheric fissures, and the third ventricle are absent.  The internal cerebral veins, superior sagittal, and the straight sinuses are absent.  The cerebellum and the brainstem are relatively normal.

Semilobar Holoprosencephaly:

This is the intermediate form of holoprosencephaly.  The two cerebral hemispheres are partially separated posteriorly.  Facial anomalies are milder than those in the lobar type and include hypotelorism and a cleft lip.  The ultrasound findings include diffuse thalami, separate rudimentary occipital and temporal horns, a singular monoventricle. There is partial development of the falx cerebri and of the interhemispheric fissure posteriorly. The splenium of the corpus callosum may develop; however, the anterior and middle portions of the corpus callosum are absent or underdeveloped.  The third ventricle is absent or small.  The fourth ventricle brainstem and cerebellum are usually normal.

Lobar Prosencephaly:

Facial anomalies are often absent or mild and similar to the semilobar form.  Ultrasound shows squared, fused frontal horns with angular corners and flat roofs.  There is absence of the septum pellucidum; however, the thalami are normal bilaterally and are not fused.  The lateral ventricles are well formed posteriorly with separate occipital and temporal horns.  The bodies of the lateral ventricles may be closely positioned.  The anterior interhemispheric fissure is present but may be shallow.  The corpus callosum is often incomplete.  The posterior fossa structures, third ventricle, posterior interhemispheric fissure, and the falx cerebri are normal.