by Justin Lee

Created on: April 02, 2009

Holoprosencephaly is a congenital condition resulting from the incomplete separation of the embryonic forebrain into two distinct hemispheres. During normal development, the cerebral hemispheres, thalamus, and hypothalamus begin to develop bilaterally from a single forebrain structure during the fifth week of gestation. Failure of the two cerebral hemispheres to separate results in holoprosencephaly.

Holoprosencephaly ranges from mild to severe depending upon the degree of separation of the hemispheres. The three categories (from most severe to least severe) are: (1) alobar holoprosencephaly, in which the brain fails to divide, resulting in a single ventricle and fused cerebral hemispheres; (2) semilobar holoprosencephaly, in which the two hemispheres separate partially; and (3) lobar holoprosencephaly, in which the ventricles are completely separated and only discrete areas of brain matter fail to separate.

Midline facial defects usually accompany the brain malformation, indicate the degree of holoprosencephaly, and are important in prognoses. The most severe facial manifestation is cyclopia, a condition where the patient has a single eye in the midline and a proboscis (a tubular, snout-like nose). There may also be ocular hypotelorism, which is an abnormal narrowing of the bridge of the nose and decreased distance between the eyes, and premaxillary agenesis (cleft lip or cleft palate).

Other symptoms of holoprosencephaly include: inability to smell (anosmia), small head (microcephaly), excessive fluid in the brain (hydrocephalus), varying degrees of mental retardation, epilepsy, pituitary and hypothalamus dysfunction, endocrine abnormalities, and organ systems abnormalities.

Holoprosencephaly occurs with a rate of 1 in 250 during embryogenesis, but due to the high rate of fetal mortality, presents as 1 in 10,000-20,000 neonates.

Active research into the etiology of holoprosencephaly has indicated multiple teratogenic and genetic causes. The Sonic Hedgehog (Shh) protein is most frequently mutated in familial holoprosencephaly. Trisomy 13 and trisomy 18 are most frequent chromosomal abnormalities.

The preferred imaging technique for holoprosencephaly is cranial magnetic resonance imaging (MRI), though ultrasonography and cranial computed tomography (CT) scanning are used as well. There is no standard treatment for holoprosencephaly and the prognosis depends on the severity of the brain and cranial malformations. The majority of infants born with holoprosencephaly do not live beyond the first six months of life, and those born with cyclopia usually do not live beyond the first week. Neonates born with the mildest cranial and facial abnormalities can live a normal life span.

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