The holoprosencephaly (HPE) corresponds to a severecongenital malformation and complex brain associated obvious facial abnormalities and individuals as hypotelorism, cyclopia, ethmocephaly, cleft lip, etc.


Definition of holoprosencephaly

It is a birth defect of the brain that is also related to malformations of the face and skull. This malformation that occurs during the first weeks of gestation of the fetus , is characterized by a lack of division of the front part of the brain which prevents the cerebral hemispheres (right and left) from developing correctly and in the lateral ventricles (cavities of the brain in which the cerebrospinal fluid is found).

  • Causes of holoprosencephaly
  • Diagnosis
  • Treatment of holoprosencephaly
  • Types of holoprosencephaly
  • Alobar holoprosencephaly
  • Semilobar holoprosencephaly
  • Lobar holoprosencephaly

Causes of holoprosencephaly

No particular cause for holoprosencephaly has been identified. It is said that it could be of teratogenic origin , in other words, that a substance or medically produce a congenital defect during embryonic development. Likewise, this abnormality has been associated with alcohol consumption and diabetes in the mother because these conditions affect the cells of the midline of craniofacial structures.


Some babies will have an identifiable genetic cause. About a third of children born with this disease have an abnormality in the chromosomes that contain genetic material (DNA).

Other risk factors are related to infections during pregnancy such as syphilis, toxoplasmosis, herpes, and rubella. In the same way, the consumption of substances such as aspirin, lithium, anticonvulsants and hormones could influence the development of this malformation.

Recent studies show the possibility that lipid-lowering drugs of the statin class may be involved in the onset of the disease.


Given that it is associated with a few months of life, a prenatal diagnosis could be very useful to make decisions about the development of the pregnancy. This abnormality could be linked to different syndromes that affect many body systems. In this sense, it is vitally important that the specific nature of the disease be identified at the clinical level.

It can be detected through physical examination , however, MRI is required to give a definitive diagnosis . Likewise, it is necessary to carry out a genetic test because in almost half of the cases there are chromosomal abnormalities, particularly those that alter chromosome 13.

Prenatal diagnosis is easier in the case of alobar or semilobar holoprosencephaly and can be performed through morphological ultrasound from the tenth week of pregnancy. On the other hand, in the case of lobar holoprosencephaly, its diagnosis tends to be more difficult and later. A medical termination of pregnancy is accepted in most cases of holoprosencephaly.

Treatment of holoprosencephaly

There is no curative treatment. Indeed, in severe cases, it is important to consider the limitations of the medicine as the disease could be fatal. On the other hand, in mild cases, treatment can be multidisciplinary in nature and encompass different medical specialties such as neurology, endocrinology, and physiotherapy, among others.

In the latter cases, the treatments are palliative and adapted to the symptoms present . For example, medications can be used to prevent spasticity, difficulty sleeping, or esophageal sphincter problems.

Types of holoprosencephaly

There are different types of holoprosencephaly depending on the extent of the malformation. This malformation leads to more or less important facial abnormalities. Intellectual retardation is frequently present. Patients with the most severe forms only live for a few months.

Alobar holoprosencephaly

It is the most severe form of holoprosencephaly characterized by an abnormality in prosencephalization . As a consequence of this, there is a fusion of the two cerebral hemispheres and a single centrally located ventricle. Similarly, the brain tends to be smaller than normal size and the thalamus are fused.

Signs such as anophthalmia, cyclopia, severe mental retardation, cleft lips, cleft lip, epileptic seizures, and microcephaly are present. Indeed, at the clinical level, patients with alobar holoprosencephaly present more obvious facial malformations and even the level of severity of the disease can be so high that spontaneous abortion or death occurs in utero.

Semilobar holoprosencephaly

In this case, the prosencealization is interrupted which allows the fusion of the hemispheres at an anterior level. The hemispheres are partially separated. As there is an incomplete fissure in the interhemispheric zone, the occipital lobes and horns present only mild anomalies. This form of the disease is characterized by nasal malformations and a variable degree of mental retardation .

Lobar holoprosencephaly

This is the least severe of the classic forms of holoprosencephaly with separation of the right and left hemispheres and the lateral ventricles and with fusion of the frontal lobes mainly anterior and ventral.

Lobar holoprosencephaly is associated with mild or absent facial malformations or intellectual abilities that can range from mild to normal mental retardation . In addition, there may be an abnormality in the corpus callosum.

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