Summary: A healthy 21-year-old parity 1, gravida 0 (P1G0) woman woman presented
for a 20-week screening ultrasound. Her pregnancy had been uneventful up
until the time of the ultrasound.
Alobar holoprosencephaly with cyclopia
The obstetric ultrasound images of the fetal face demonstrate a
single midline orbit (Figure 1). Axial imaging of the fetal brain shows
fused thalami (Figure 2). Coronal imaging of the brain (Figure 3)
demonstrates a monoventrical with lack of interhemispheric fissure and
falx cerebri. At birth a single midline orbit and a probiscus were
present. The baby died shortly after birth. An autopsy was not performed
and no chromosomal evaluation was undertaken.
The holoprosencephalies are a group of disorders that develop as a
result of abnormal differentiation and cleavage of the prosencephalon.
Holoprosencephalies are commonly divided into three subcategories based
on severity: alobar, semilobar, and lobar. In lobar holoprosencephaly,
the mildest form, the brain typically has formation of a partial frontal
horn and the posterior half of the callosal body as well as a fully
formed third ventricle. In the semilobar form, the posterior portions of
the brain including the interhemispheric fissure and the falx cerebri
are partially formed whereas the anterior brain is fused. Alobar
holoprosencephaly is the most severe form and usually leads to
stillbirth or death shortly after birth.
In alobar holoprosencephaly there is limited formation of the
anterior portion of the brain. The brain of affected patients commonly
lacks a falx cerebri, an interhemispheric fissure and a corpus callosum.
In addition, there is absence of the third ventricle as the thalami are
fused. The cerebrum is only partially formed and is located in the
rostral calavarium. A large dorsal cyst occupies the majority of the
clavarium. In most cases of alobar holoprosencephaly, patients have
obvious midline facial deformities, such as midfacial clefts, a
primitive nasal structure and hypotelorism. In the most extreme forms
there is fusion of the globes and orbits, which results in cyclopia.
Because of the severe malformations present in alobar holoprosencepahly,
it is diagnosed by ultrasound more commonly than the other forms.
The etiology of the holoprosencephalies is heterogeneous and has
been attributed to both environmental and genetic causes. Veratrum
alkaloids and distal inhibitors of cholesterol biosynthesis are
teratogens that have been associated with holoprosencephaly. The
malformation is frequently due to microdeletions or duplications within
the genes responsible for forebrain development. Holoprosencephaly has
also been associated with triploidy, trisomy 13, trisomy 18, and a
number of other syndromes.
The prevalence of holoprosencephaly varies considerably depending
on the point during gestation at which it is measured. In a large
epidemiologic study, Croen et al found the prevalence of
holoprosencephaly to be 1.2 per 10,000 live births and fetal deaths.
This figure was supported by a recent study by Bullen et al that found
the total prevalence, including terminations, was 1.2 cases/10,000
registered births. This same study found the birth prevalence, which
included stillbirths and live births > 24 weeks, to be 0.49
Holoprosencephaly is a rare congenital anomaly that is characterized by
lack of cleavage of the prosencephalon. Holoprosencephaly can frequently
be diagnosed via screening ultrasound at 20 weeks gestation. The
diagnosis should be considered in fetuses and infants who have midline
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