Holoprosencephaly is an abnormality of brain development in which the brain doesn't properly divide into the right and left hemispheres. The condition can also affect development of the head and face. There are 4 types of holoprosencephaly, distinguished by severity. From most to least severe, the 4 types are alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In general, the severity of any facial defects corresponds to the severity of the brain defect. The most severely affected people have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. In the less severe forms, the brain is only partially divided, and the eyes usually are set close together. Other signs and symptoms often include intellectual disability and pituitary gland problems. Holoprosencephaly can be caused by mutations in any of at least 14 different genes; chromosome abnormalities; or agents that can cause birth defects (teratogens). It may also be a feature of several unique genetic syndromes. In many cases, the exact cause is unknown. Life expectancy for people with this condition varies, and treatment depends on the symptoms and severity in each person.
Last updated: 5/10/2016
What are the signs and symptoms of holoprosencephaly?
Holoprosencephaly can present within a broad variety of clinical severity. Holoprosencephaly is classified into into 3 subtypes based upon the degree of cerebral hemisphere separation: lobar, semilobar, and alobar and a fourth subtype, the middle interhemispheric (MIH) variant:
Alobar holoprosencephaly results from complete failure of the brain to divide into right and left hemispheres and there is a single “monoventricle” (instead of two). The findings may include a single eye (cyclopia) with a tubular-shaped nose (proboscis); or ethmocephaly (extremely closely spaced eyes but separate orbits with proboscis between the eyes); or absent (anophthalmia) or very small eye (microophthalmia); or cleft lip, closely spaced eyes and a flattened nose; or bilateral cleft lip, and in some cases a relative normal facial appearance (especially in persons with mutations in the ZIC2 gene)
Semi-lobar holoprosencephaly occurs when the left side of the brain is fused to the right side in the areas of the brain known as the frontal and parietal lobes. Also, the dividing line between the right and left hemispheres of the brain (the interhemispheric fissure) is only present in the back. Individuals with semi-lobar holoprosencephaly may have eyes that are set close together (hypotelorism), and their eyeballs may be abnormally small (microphthalmia) or absent (anophthalmia). Additional features may include a flattened bridge and tip of the nose, one nostril, a cleft lip that occurs in the middle (median cleft lip) or on both sides (bilateral cleft lip), and a cleft palate.
Lobar holoprosencephaly: There are two ventricles (right and left) but cerebral hemispheres are fused in the frontal cortex. Features may include bilateral cleft lip with median process, closely spaced eyes, depressed nose or relative normal face.
Middle interhemispheric variant resulsts when the brain is fused in the middle. Signs may include closely spaced eyes, depressed and narrow nose or relatively normal face.
Other signs and symptoms commonly observed in children with holoprosencephaly include seizures, hydrocephalus, neural tube defects, pituitary dysfunction, short stature, feeding difficulties, and instability of temperature, heart rate, and respiration. Most people with holoprosencephaly have developmental delay and intellectual disability, the severity of which is related to the severity of the brain malformation.
Holoprosencephaly may be one feature of several genetic syndromes which each having unique characteristic.
Last updated: 8/25/2015
What is the prognosis for holoprosencephaly?
The prognosis depends on the sub-type. The alobar holoprosencephaly is the most severe type of the defect and the affected fetus are usually stillbirth, or die soon after birth, or during the first 6 months of life. However, a significant proportion of more mildly affected children (as well as some severely affected children) survive past age 12 months. More than 50 percent of children with semi-lobar or lobar holoprosencephaly without significant malformations of other organs are alive at age 12 months. The life expectancy for individuals with semi-lobar holoprosencephaly depends on the underlying cause of the condition and the presence of associated anomalies.
Last updated: 2/24/2016
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