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The patient is a 5-month-old infant with hypotelorism, a
cleft palate, and delayed milestones.
Definition/Background
Holoprosencephaly (HPE) is a complex group of malformation
disorders characterized by a failure of differentiation and cleavage of the
prosencephalon, occurring between the 18th and the 28th day of gestation, and affecting
both the forebrain and the face. HPE has been associated with both teratogenic
(such as maternal diabetes) and genetic causes. Sonic hedgehog (SHH), ZIC2,
SIX3, TGIF, PTCH, GLI2, and TDGF1 genes have been positively implicated in HPE.
This disorder can also be due to chromosomal abnormalities, with a higher
prevalence observed in trisomy 13 (Patau’s syndrome), and less commonly in
trisomy 18 (Edward’s syndrome) and triploidy. Classically, three levels of increasing
severity are described: lobar, semilobar, and alobar. Another milder subtype of
HPE, the middle inter-hemispheric variant (MIH), or syntelencephaly, has also been
recognized.
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Characteristic
Clinical Features
HPE is generally associated with craniofacial anomalies, such
as hypotelorism, midline cleft lip and/or palate, cebocephaly (flattened nose
with single nostril), single maxillary central incisor and microcephaly. In
severe cases, anophthalmia, cyclopia, or proboscis (ethmocephaly), can be
present. The most common neurologic sign is developmental delay. Other commonly
seen signs include mental retardation, epilepsy, weakness, spasticity,
dystonia, and choreoathetosis. Endocrine disorders (diabetes insipidus or growth
hormone deficiency), oro-motor dysfunction (feeding and swallowing
difficulties) and autonomic dysfunction (instability of temperature, heart,
and/or breath rate) may also be seen. Usually the degree of craniofacial and
neurologic abnormalities cor-relates with the severity of the brain
malformation.
Characteristic
Radiologic Findings
Alobar Holoprosencephaly: Presents a pancake-like cerebrum,
without interhemispheric division; large monoventricle that can communicate
with a dorsal cyst; absence of olfactory bulbs and tracts (arrhinen-cephaly);
absence of corpus callosum; and fusion of deep gray nuclei.
Semilobar Holoprosencephaly: Shows rudimentary cerebral lobes,
with incomplete interhemispheric division (IHF and falx present posteriorly
only); presence of posterior ventricle horns with small third ventricle; absence
or hypoplasia of olfactory bulbs and tracts; presence of splenium of corpus
callosum; partial fusion of thalami and basal ganglia; and dorsal cyst.Lobar
Holoprosencephaly: Presents with almost normal lobar differentiation and
separation of the hemispheres, with the exception of midline continuity of the
basal frontal cortex; IHF and falx hypoplastic anteriorly and presenting
posteriorly; rudimentary anterior horns of the ventricles; presence of splenium
of corpus callosum, and variable presence of anterior body with hypoplasia of
the genu of corpus callosum; usually fully separated thalami; and variable
degree of fusion of the basal ganglia.
Middle Interhemispheric Variant of Holoprosencephaly (MIH):
Shows failure of separation of the posterior frontal and parietal lobes; normal
or hypoplasic ante-rior horns; presence of genu and splenium of corpus callosum
with absence of callosal body; fully separated hypothalamus and basal ganglia;
and variable fusion of thalami. Cortical dysplasia and heterotopic gray matter
are also common findings.
Primary Differential
Diagnosis
1-Septo-Optic Dysplasia
Discussion of
Differential Diagnosis
Septo-Optic Dysplasia (SOD): Consists of hypoplasia of the
optic nerves and hypoplasia or absence of the septum pellucidum. Schizencephaly
and gray matter heterotopias may be present. However, some authors consider
that some patients with SOD have a mild form of holoprosencephaly.
   
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Labels: Brain
