Diagnostic ultrasound ( PDFDrive )

CHAPTER 34 The Fetal Brain 1187
Cerebral hemisphere development starts at about 5 weeks
with prechordal mesoderm migration into the area anterior to
the notochord where under genetic control it induces midface
and forebrain development. Normally apoptosis of midline areas
results in separation of facial and prosencephalic structures into
let and right sides by 5 weeks. he failure to separate by apoptosis
results in the fused cerebral and facial appearances of HPE. he
severity of facial dysmorphism correlates with cerebral abnormalities
in about 80% of cases (“the face predicts the brain”). Not
surprisingly, additional abnormalities involving any part of the
brain and body are found in about 50% to 65% of cases. 149-153
HPE etiology and phenotype are heterogeneous and result
from multiple varied genetic and environmental “hits” to the
development process. HPE is part of diferent syndromes and
about 40% have chromosomal abnormalities, but many cases
are sporadic and without etiologic explanation. 150-152,154
Factors Associated With
Holoprosencephaly 149-151,153
Environmental teratogens: alcohol, smoking, retinoic acid,
salicylates, anticonvulsants
Metabolic: insulin-dependent diabetes (1% risk)
Infections: cytomegalovirus, toxoplasmosis, rubella
Syndromes with normal karyotype (about 25% of
holoprosencephaly)
Smith-Lemli-Opitz
Pallister-Hall
Velocardiofacial
Meckle
Chromosomal abnormalities
Trisomy 13 (70% have holoprosencephaly)
Trisomy 18
Triploidy
Gene mutations
SHH (Sonic Hedgehog; expressed in notochord and
loor plate of neural tube)
ZIC2 (has role in neurulation in dorsal midline)
Unexplained/sporadic (50%-65%)
Isolated HPE can have autosomal dominant inheritance with
incomplete penetrance and variable expression. Parents of afected
children should be examined for mild manifestations such as
single central incisor and absent nasal cartilage. 153-155
HPE is a continuous malformation that is classically divided
by DeMyer 156 into three overlapping phenotypic types depending
on severity: alobar (75% of cases, monoventricular, face typically
abnormal), semilobar (10% of cases, anterior hemispheres fail
to separate but there are two posterior lobes), and lobar (10%
of cases, two hemispheres form, but the anterior forebrain is
incompletely separated). About 5% are atypical forms, including
a midline interhemispheric form (syntelencephaly). Severe
cases oten have a dorsal cyst, the dilated suprapineal recess of
the third ventricle dilation secondary to obstruction of CSF low
by thalamic fusion 149,151-154 (Fig. 34.16, Video 34.7). he range of
abnormalities is much larger than these simple categorizations
suggest, involving not only the cerebrum but also basal ganglia
and other lower areas. Furthermore, there are microforms of
HPE with mild manifestations such as single midline incisor
tooth, hypotelorism, or absence of olfactory lobes. 149,151-154
General Anatomic Classiication of
Holoprosencephaly 151,153
ALOBAR
Single forebrain ventricle
No interhemispheric division
Absent olfactory tracts
Absent corpus callosum
Nonseparation (fusion) of deep gray nuclei
Dorsal cyst
Facial abnormality common
SEMILOBAR
Rudimentary cerebral lobes
Incomplete anterior hemisphere division
Absent or small olfactory tracts
Absent anterior corpus callosum (posterior part may
develop)
Variable nonseparation of deep gray nuclei
LOBAR
Fully developed cerebral lobes
Distinct interhemispheric division
Midline continuous frontal neocortex
Corpus callosum absent, hypoplastic, or normal
Separation of deep gray nuclei
Fused fornices
Azygous (wandering) anterior cerebral artery
MIDLINE INTERHEMISPHERIC FORM
(SYNTELENCEPHALY)
Failed separation of parietal hemispheres
Vertical sylvian issure appearing to connect across the
midline at the vertex
Anterior and posterior corpus callosum formed
Absent or abnormal central corpus callosum
Normal separation of hypothalamus and lentiform nuclei
Gray matter heterotopia
Prenatal diagnosis is based mainly on imaging indings. 149,154
HPE has been diagnosed as early as 9 weeks through demonstration
of a single ventricle, single orbit, and proboscis. 152,153 In such
early cases, it is important not to mistake the normal rhombencephalic
cavity for HPE.
In later pregnancy, typically there is absence of the CSP, variable
absence of the falx, and fused appearance of midline structures.
Alobar holoprosencephaly has three variants—pancake, cup,
and ball—depending on the size and coniguration of the dorsal
cyst. he pancake type has a small, lattened plate of cerebrum
anteriorly, with a large dorsal cyst posteriorly. he cup type has
more anterior cerebrum, forming an anterior cuplike mantle
and a dorsal cyst. he ball type has a single, featureless, monoventricle
surrounded by a mantle of ventricle of varying thickness.
With semilobar holoprosencephaly there is a rudimentary
attempt at cleavage of occipital horns (see Fig. 34.16D). Because