holoprosencephaly – alobar

holoprosencephaly – alobar

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holoprosencephaly - alobar
holoprosencephaly – alobar note the fused thalamus and monoventricle in this fetus with holoprosencephaly.
holoprosencephaly - alobar
holoprocencephaly alobar in the coronal plane an empty cranium appears but as the transducer is moved occipitally the fused thalami and absence of midline structures are apparent. the transverse view confirms these findings.

description

by the fourth week of intrauterine life the normal brain, developed from the closed neural tube, has segmented into three primary vesicles: the prosencephalon (forebrain), mesencephalon (midbrain) and rhombencephalon (hindbrain). the prosencephalon subdivides into the telencephalon and the diencephalon. the telencephalon gives rise to the cerebral cortex, the olfactory tract (rhinencephalon), part of the hypothalamus, the corpora striata, the lateral ventricles and a small portion of the third ventricle. the diencephalon develops into the thalamus, hypothalamus and the remainder of the third ventricle. the lamina terminalis, which stretches from the optic stalk to the interventricular foramen, gives rise to the corpus callosum. holoprosencephaly is a failure of embryologic development where the prosencephalon remains a single, undifferentiated structure. there is a spectrum of abnormality resulting from this in which the common findings are of hemispheric fusion, cerebral hypoplasia, olfactory bulb hypoplasia, absence of the corpus callosum and of the cavum septi pellucidi. in some cases, facial development will also affected by the failed cleavage of the prosencephalon, and again there will be a spectrum of disorder observed; in general, where the intracranial defects are minimal there are no facial anomalies, but with increasing failure of differentiation of the prosencephalon the facial defects become worse. according to the degree of incomplete division of the prosencephalic derivatives three types of holoprosencephaly are recognised. alobar, the most severe, in which there is complete absence of the interhemispheric fissure leading to a single primitive ventricle, fused thalami, and absence of the third ventricle, neurohypophysis and olfactory bulbs. cyclopia and proboscis formation may be observed. semi-lobar, in which the two cerebral hemispheres are partially separated posteriorly, but there remains a single ventricular cavity. lobar, where the interhemispheric fissure may be well developed anteriorly and posteriorly, but there still exists a degree of fusion of some structures, such as the lateral ventricles. in addition the cavum septi pellucidi will be absent together with variable hypogenesis of the corpus callosum, which may manifest itself in disproportionate enlargement of the occipital horns (colpocephaly). antenatal differentiation of the lobar form of holoprosencephaly may be extremely difficult. further classification of the above may be made depending on the degree of failure of rotation of the prosencephalon; both alobar and semi-lobar varieties are thus further subdivided into three types: pancake, cup and ball, referring to the distribution of cerebral cortex relative to the monoventricle. reported associations have been proposed linking holoprosencephaly to ionising radiation, alkaloids, phenytoin, salicylates, toxoplasmosis and diabetes mellitus.

diagnosis

the single most valuable finding is a sickle-shaped single ventricle seen in the transverse plane with a crescent-shaped cortex anteriorly and bulb-like thalami posteriorly undivided by the third ventricle. both alobar and semi-lobar holoprosencephaly may be associated with microcephaly or macrocephaly. there is absence of the cavum septi pellucidi, the falx cerebri, and the corpus callosum. the thalami are fused. as mentioned, facial abnormalities reflect the severity of the intracranial process, cyclopia (fused orbits with supraorbital proboscis) representing the worst end of the spectrum. in general, fetal facial dysmorphism is characterised by hypotelorism, which may be found in association with a high midline proboscis (ethmocephaly), a single nostril (cebocephaly), or a defective premaxilla (median facial cleft). if any of these facial features are seen the intracranial anatomy should be carefully examined, although holoprosencephaly can occur with a normal face. it may be possible to diagnose holoprosencephaly within the first trimester using endovaginal sonography. holoprosencephaly is associated with aneuploidy in up to one third of cases, in particular trisomy 13. it may also be found with other congenital anomalies such as anencephaly, encephalocele, di george syndrome, meckel-gruber syndrome, and campomelic dysplasia. the finding of holoprosencephaly is therefore an indication for karyotyping and a detailed search for other cranial and systemic abnormalities. the prognosis in the severe forms of holoprosencephaly is hopeless; infants with isolated lobar holoprosencephaly are usually intellectually impaired.

differential diagnosis

distinction needs to be made from other conditions where there may be profound ventriculomegaly or cystic dilatation: in ventriculomegaly there are always two separate lateral ventricles and even in the severest form the cortex is thinned out evenly, in contrast to the asymmetric displacement of the cerebral cortex in alobar holoprosencephaly. midline intracranial structures (falx cerebri, interhemispheric fissure, corpus callosum, third ventricle) will usually be present in ventriculomegaly, distinguishing it from semilobar holoprosencephaly. thalamic fusion, absence of the cavum septi pellucidi, and flattening of the frontal horns will all indicate the diagnosis of lobar holoprosencephaly. distinction from hydranencephaly may be more difficult as destruction of the frontal lobes may lead to disappearance of the midline and to the presence of an extensive fluid collection anterior to the thalami. the finding of a crescent-shaped rim of cortex will indicate holoprosencephaly. facial abnormalities are not characteristic of hydranencephaly. the cyst seen in the dandy-walker malformation can displace the cortex rostrally and simulate alobar holoprosencephaly; however, a normal supratentorial ventricular system can usually be identified. the posterior fossa cyst will also demonstrate angular margins as it herniates through the tentorial notch, in contrast with the rounder monoventricular cavity of alobar holoprosencephaly.

sonographic features

monoventricle with no frontal, temporal, or occipital horns.

fused thalami.

no midline brain structures (falx cerebri, cavum septi pellucidi, corpus callosum) associated facial anomalies (midline cleft, cyclopia).

three subdivisions: ‘pancake’ – residual brain at skull base only ‘cup’ – residual brain anteriorly, not covering whole ventricle ‘ball’ – brain does not cover monoventricle, dorsal sac present.

associated syndromes

  • acalvaria
  • agnathia
  • aicardi
  • alcohol
  • aqueductal stenosis
  • brachial amelia-cleft lip/palate
  • charge association
  • chromosomal
  • craniosynostosis
  • diabetes insipidus
  • ectopia cordis
  • familial, isolated
  • goldenhar
  • grote
  • hartsfield
  • holoprosencephaly
  • holoprosencephaly
  • hydantoin
  • lambotte
  • lip synechia
  • majewski variant chondrodysplasia
  • maternal diabetes
  • meckel-gruber
  • median cleft face-other anomalies
  • pallister-hall
  • pseudotrisomy 13
  • steinfeld
  • thomas
  • velo-cardio-facial

references

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