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CAR: Anomalies - CNS

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Introduction Antenatal Postnatal West Midlands Data



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 occipital horns.
  • Lobar holoprosencephaly - the cerebral hemispheres are separated anteriorly and posteriorly with some degree of fusion of structures.

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 fetal hydrops.

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

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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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© Perinatal Institute 2011