When we imagine a brain, whether it is human or not, the image that comes to mind is generally composed of an organ whose outer layer is plagued by folds, among which we can see some cracks that allow us to appreciate the presence of two halves or hemispheres of the brain.
Such separation is something that most human beings have, forming during our fetal development. But not all: there are children whose brain is not divided or whose hemispheres are fused: we are talking about children who suffer from holoprosencephaly .
Holoprosencephaly: what is it?
Holoprosencephaly is a type of malformation along the fetal development in which there is no division between the different structures of the prosencephalon: there is a fusion between the cerebral hemispheres, as well as between some subcortical structures and the cerebral ventricles. This fusion, or rather non-separation, can occur at a complete or partial level (with the hemispheres being completely fused or only in some parts).
Generally, the division of the brain into different lobes and hemispheres occurs around the fourth week of gestation. In holoprosencephaly this division does not occur or is not completed, which has severe repercussions both before and after birth. This condition usually comes together with the presence of cranial and facial malformations, with alterations such as hypertelorism or eyes together, cyclopia or only one eye, alterations of the nose, cleft lip, cleft palate or hydrocephalus. Likewise, it is frequent that problems appear in the feeding and in the thermal maintenance, cardiac and respiratory alterations and convulsions. It is also associated with different degrees of intellectual disability, in cases that are mild enough to allow for life.
Generally, holoprosencephaly has a very poor prognosis, especially in the allobar type: children usually die either before birth or before the age of six months . In the other types, survival is possible up to one or two years of age. Depending on whether there are other complications and the severity of the disorder. In the mildest cases, survival is possible, although they will usually suffer from cognitive deficits to a greater or lesser extent.
Some of its main variants
Holoprosencephaly is a medical condition that can present itself in different ways, depending on the possible degree of separation of the cerebral hemispheres. There are three main variants, the most common, although it must be taken into account that there are others. These types of holoprosencephaly are the following .
1. Lobar holoprosencephaly
Wolf holoprosencephaly is the mildest form of this type of disorder. In this case we can observe the presence of almost perfectly separated lobes , although this separation has not been carried out in the frontal lobes and they do not usually have septum pellucidum.
2. Semi-wolf holoprosencephaly
In this variant of holoprosencephaly there is a division between the hemispheres in part of the brain, but the frontal and parietal lobes are fused. The interhemispheric cleft is only observed in the temporal and occipital .
Hypotelorism is often present, meaning that the baby’s eyes are much less separated than usual, that they are small or that they do not exist at all. Cleft lip or palate may also be observed, as well as absence or malformations at the nasal level.
3. Holoprosencephaly allobar
This is the most severe form of holoprosencephaly, in which the hemispheres do not separate at all, being completely fused together. It is common for there to be a single ventricle and/or a single thalamus.
Many of these children are also born with only one eye, in which case the existence of cyclopia is considered. In fact, the emergence of the mythical figure of the cyclops was probably based on the observation of some case of this type of holoprosencephaly. The nose usually has malformations, and may have a proboscis formation or even no nostril (something that can cause the child to asphyxiate) or only one of them.
4. Interhemispheric holoprosencephaly
This variant, less common than the previous three, occurs when the division of the brain does not occur in the middle: the back parts of the frontal and parietal lobes. There is no corpus callosum (with the possible exception of the genu and splenius), although generally at the level of subcortical structures there is no overlap or fusion . Also called synthelephaly.
Although technically it would no longer be holoprosencephaly, aprosencephaly, in which the prosencephalon does not directly form, is also sometimes considered a variant of this disorder.
Causes of this problem
Holoprosencephaly is an alteration that occurs during fetal development. There are a variety of possible factors that can lead to its occurrence. A large number of cases have been observed in which there are genetic alterations in numerous genes (one in four has alterations in the genes ZIC2, SIC3, SHH or TGIF), as well as different syndromes and chromosomal disorders (Patau’s syndrome or Edwards’ syndrome among them).
A link to environmental factors, such as uncontrolled diabetes in the mother or the abuse of alcohol and other drugs, as well as the use of some medications, has also been observed.
This condition, usually genetic, has no curative treatment. The treatments to be applied will generally be of a palliative nature , aimed at maintaining your vital signs, correcting difficulties and improving your well-being and quality.
In mild cases that achieve survival, the use of occupational therapy and cognitive stimulation is recommended. The need to apply a multidisciplinary treatment involving professionals from different disciplines, both medicine and occupational therapy, clinical psychology, physiotherapy and speech therapy, should be assessed. And this without neglecting the treatment to parents and environment (which will require psychoeducation and counseling, as well as possibly a psychological intervention).
- Monteagudo, A. & Timor-Tritsch, I.E, (2012). Prenatal diagnosis of CNS anomalies other than neural tube defects and ventriculomegaly (online). Available at: http://cursoenarm.net/UPTODATE/contents/mobipreview.htm?9/28/9665/abstract/4-12
- Cohen, M.M. & Sulik, K.K. (1992). Perspectives on holoprosencephaly: Part II. Central nervous system, craniofacial anatomy, syndrome commentary, diagnostic approach, and experimental studies. J. Craniofac. Genet. Dev. Biol., 12:196.