Holoprosencephaly: types, symptoms and treatments

This type of congenital malformation appears when the parts of the brain are not well divided.

When we imagine a brain, whether human or not, the image that comes to mind is generally composed of an organ whose outer layer is riddled with folds, between which we can see some indentations that allow us to appreciate the presence of two halves or cerebral hemispheres.

This separation is something that most human beings have, being formed during our fetal development. But not all of them: there are children whose brain is not divided or whose hemispheres are fused: we are talking about children with holoprosencephaly..

Holoprosencephaly: what is it?

Holoprosencephaly is the name given to a type of malformation along the fetal development. in which there is no division between the different structures of the forebrain: 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 may be complete or partial (the hemispheres being fused completely 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 either does not occur or fails to be completed, which has severe repercussions both before and after birth. This condition usually comes along with the presence of cranial and facial malformations, with alterations such as hypertelorism or eyes together, cyclopia or one eye, nose alterations, cleft lip, cleft palate or hydrocephalus. It is also common to find problems in feeding and thermal maintenance, cardiac and respiratory alterations and convulsions. It is also associated with varying degrees of intellectual disability, in cases mild enough to be life-threatening.

In general, holoprosencephaly has a very poor prognosis, especially in the allobar type: the children usually die or die before birth. 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 life. Depending on whether there are other complications and the severity of the disorder. In milder cases, survival is possible, although they will usually suffer cognitive deficits to a greater or lesser extent.

Some of its main variants

Holoprosencephaly is a medical condition that can present itself in different forms, depending on the possible degree of separation of the cerebral hemispheres. The first three variants are the most common, although it should be noted that there are others. These types of holoprosencephaly are as follows.

1. Lobar holoprosencephaly

Lobar holoprosencephaly is the mildest form of this type of disorder. In this case, the following can be observed the presence of almost perfectly separated lobesHowever, this separation has not been carried out in the frontal lobes and they usually do not have septum pellucidum.

2. Semilobar 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 fissure is only seen in the temporal and occipital lobes..

Hypotelorism, i.e. the baby's eyes are much less separated than usual, they are small or do not exist at all. Cleft lip or cleft palate may also be observed, as well as absence or malformations at nasal level.

3. Holoprosencephaly alobar

This is the most severe form of holoprosencephaly, in which the hemispheres do not separate to any degree, being completely fused. There is often a single ventricle and/or a single thalamus. and/or a single thalamus.

Many of these children are also born with only one eye, in which case cyclopia is considered to be present. In fact, the emergence of the mythical figure of the cyclops was probably based on the observation of a case of this type of holoprosencephaly. The nose is usually malformed and may have a proboscis-like formation or even no nostril (which can lead to suffocation of the child) or only one nostril.

4. Interhemispheric holoprosencephaly

This variant, less common than the previous three, occurs when the division of the brain does not occur in the middle part: the posterior parts of the frontal and parietal lobes. There is no corpus callosum (with the possible exception of the genu and the splenium), although there is generally no overlap or fusion at the level of subcortical structures.. Also called syntelencephaly.

5. Aprosencephaly

Although technically no longer holoprosencephaly, aprosencephaly, in which the forebrain fails to form, is sometimes considered a variant of this disorder.

Causes of this problem

Holoprosencephaly is a disorder that occurs during fetal development, and there are a variety of possible factors that can lead to its occurrence. It has been observed the existence of a large number of cases in which there are genetic alterations in numerous genes. there are genetic alterations in numerous genes (one in four has alterations in the ZIC2, SIC3, SHH or TGIF genes), as well as different syndromes and chromosomal disorders (Patau syndrome or Edwards syndrome among them).

A link has also been observed with environmental factors, such as uncontrolled Diabetes in the mother or the abuse of alcohol and other drugs, as well as the consumption of some medications.

Treatment

This condition, generally genetic, has no curative treatment. The treatments to be applied are generally of a palliative nature.The treatment is aimed at maintaining their vital signs, correcting difficulties and improving their wellbeing and quality of life.

In mild cases that survive, the use of occupational therapy and cognitive stimulation is recommended. The need to apply a multidisciplinary treatment involving professionals from different disciplines, such as medicine, occupational therapy, clinical psychology, physiotherapy and speech therapy, should be assessed. And this without neglecting the treatment of parents and environment (which will require psychoeducation and counseling, as well as possibly a psychological intervention).

Bibliographical references:

• 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.