HOLOPROSENCEPHALY is a disorder characterized by the failure of the prosencephalon (the forebrain of the embryo) to develop. During normal development the forebrain is formed and the face begins to develop in the fifth and sixth weeks of pregnancy. Holoprosencephaly is caused by a failure of the embryo’s forebrain to divide to form bilateral cerebral hemispheres (the left and right halves of the brain), causing defects in the development of the face and in brain structure and function.
There are three classifications of holoprosencephaly.
- Alobar holoprosencephaly, the most serious form in which the brain fails to separate, is usually associated with severe facial anomalies.
- Semilobar holoprosencephaly, in which the brain’s hemispheres have a slight tendency to separate, is an intermediate form of the disease.
- Lobar holoprosencephaly, in which there is considerable evidence of separate brain hemispheres, is the least severe form. In some cases of lobar holoprosencephaly, the patient’s brain may be nearly normal.
Holoprosencephaly, once called arhinencephaly, consists of a spectrum of defects or malformations of the brain and face. At the most severe end of this spectrum are cases involving serious malformations of the brain, malformations so severe that they are incompatible with life and often cause spontaneous intrauterine death. At the other end of the spectrum are individuals with facial defects–which may affect the eyes, nose, and upper lip–and normal or near-normal brain development. Seizures and mental retardation may occur.
The most severe of the facial defects (or anomalies) is cyclopia, an abnormality characterized by the development of a single eye, located in the area normally occupied by the root of the nose, and a missing nose or a nose in the form of a proboscis (a tubular appendage) located above the eye.
Ethmocephaly is the least common facial anomaly. It consists of a proboscis separating narrow-set eyes with an absent nose and microphthalmia (abnormal smallness of one or both eyes).
Cebocephaly, another facial anomaly, is characterized by a small, flattened nose with a single nostril situated below incomplete or underdeveloped closely set eyes.
The least severe in the spectrum of facial anomalies is the median cleft lip, also called premaxillary agenesis.
Although the causes of most cases of holoprosencephaly remain unknown, researchers know that approximately one-half of all cases have a chromosomal cause. Such chromosomal anomalies as Patau’s syndrome (trisomy 13) and Edwards’ syndrome (trisomy 18) have been found in association with holoprosencephaly. There is an increased risk for the disorder in infants of diabetic mothers.
There is no treatment for holoprosencephaly and the prognosis for individuals with the disorder is poor. Most of those who survive show no significant developmental gains. For children who survive, treatment is symptomatic. It is possible that improved management of diabetic pregnancies may help prevent holoprosencephaly, however there is no means of primary prevention.