The upper part of the brain that performs the higher functions is normally
divided into two halves, the cerebral hemispheres. The two sides of the brain
communicate via the corpus callosum, but the two sides are essentially separate
entities with brain tissue surrounding a central fluid filled chamber, the
lateral ventricle, on each side. Holoprosencephaly is the absence or incomplete
cleavage of the forebrain (prosencephalon) into the two cerebral hemispheres.
This process usually takes place during the third week of fetal life.
There are three types of holoprosencephaly classified by the degree of division:
- Alobar holoprosencephaly (arhinencephaly)
- there is no evidence of division of cerebral
cortex, i.e. a single forebrain with a single
ventricle instead of two cerebral hemispheres
with lateral ventricles, fusion of thalami, and
only a rudimentary corpus callosum.
- Semilobar holoprosencephaly -
there is only partial cleavage with the cerebral
hemispheres fused at the frontal region only,
the brain has a horseshoe appearance single central
ventricle. There are variable degrees of fusion
of the thalami and absent olfactory bulbs and
corpus callosum, a single ventricle with rudimentary
- Lobar holoprosencephaly - the
cerebral hemispheres are separated anteriorly
and posteriorly with some degree of fusion of
Facial and ocular development are
linked to the differentiation of the forebrain
and therefore deformities of the face and eyes
are frequently present in cases of holoprosencephaly.
These include cebocephaly (hypotelorism, single
nostril), cyclopia (fused or nearly fused orbits
with supra-orbital proboscis), ethmocephaly (hypotelorism,
high midline proboscis), arhinia (no fetal nose),
coloboma of the iris and retina, microphthalmus,
premaxillary agenesis (hypotelorism with absent
nares and philtrum) and midline facial clefts.
Defects of other systems may also occur including congenital heart defects
(ASD, VSD, and truncus arteriosus), dysplastic testes and genitalia, cystic
kidneys, malrotation of gut, polydactyly, exomphalos, renal dysplasia, and
Holoprosencephaly may present as
an isolated malformation of the central nervous
system or as part of a syndrome. It is often described
as "holoprosencephaly sequence" where
a series of events flow a single initial abnormality.
A primary embryological defect in the forebrain
leads to microcephaly, absent olfactory and optic
nerves, and midline facial defects.
Holoprosencephaly is common in
chromosome anomalies, particularly trisomies 13,
13/15, 18, and 21 and triploidy. Holoprosencephaly
is also present in some syndromes such as Smith-Lemli-Opitz
syndrome and Meckel-Gruber syndrome (autosomal
recessive). There are also known associations with
several teratogens (alcohol, irradiation, and toluene)
and there is a higher incidence in infants of diabetic
mothers. An inherited from also exists with only
a mild manifestation, sometimes a single central
incisor, in one of the parents.
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The communication of the two lateral
ventricles gives a characteristic appearance on
ultrasound with a single, usually anterior fluid
filled chamber, with the thalamus fused and prominent
in the midline. The thalamus is not in itself abnormal,
but the ease with which it is seen is caused by
the failure of normal brain development of the
medial wall of each lateral ventricle. There is
often associated hydrocephalus, an excess of fluid
within the cerebral ventricles. The choroid plexus
normally grows from the medial wall to fill the
lateral ventricles, but in holoprosencephaly, this
process is abnormal. The choroid plexus may not
develop, or in some cases, it can develop and under
the forces of gravity fall from the upper to the
lower half of the common ventricular chamber. This
can be confusing, but in fact confirms the diagnosis,
verifying the communication between the two sides
of the cerebral cortex.
Alobar and semilobar holoprosencephaly can be diagnosed prenatally, as there
is no midline echo of the fetal head generated by inter-hemispheric fissure.
In alobar holoprosencephaly, a single sickle-shaped ventricle in the frontal
portion or the cerebrum can be seen. Lobar holoprosencephaly is not easily diagnosed.
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The prognosis for holoprosencephaly
depends on the severity of the lesion. There is
a high attrition rate during pregnancy and many
cases abort spontaneously. Cases of alobar holoprosencephaly
are lethal within the first year of life. Infants
with semilobar holoprosencephaly have a poor prognosis
however some cases survive into infancy many with
amentia. Cases of lobar holoprosencephaly may have
a normal life expectancy but with severe mental
and physical impairment.
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West Midlands Data
Information to follow
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