Learning About Holoprosencephaly

National Human Genome Research Institute

National Institutes of Health
U.S. Department of Health and Human Services


Learning About Holoprosencephaly (HPE)

What do we know about holoprosencephaly?

Holoprosencephaly (HPE) is a relatively common birth defect of the brain, which often can also affect facial features, including closely spaced eyes, small head size, and sometimes clefts of the lip and roof of the mouth, as well as other birth defects. Holoprosencephaly is a disorder caused by the failure of the prosencephalon (the embryonic forebrain) to sufficiently divide into the double lobes of the cerebral hemispheres. The result is a single-lobed brain structure and severe skull and facial defects. In most cases of holoprosencephaly, the malformations are so severe that babies die before birth. In less severe cases, babies are born with normal or near-normal brain development and facial deformities that may affect the eyes, nose and upper lip.

This birth defect occurs soon after conception. It has a prevelance of 1 in 250 during early embryo development, and 1 in 10,000 to 1 in 20,000 at term.

There are three classifications of holoprosencephaly:

The milder craniofacial characteristics of HPE include microcephaly, midface flattening, hypotelorism (closely spaced eyes), flat nasal bridge, and single maxillary central incisor. Approximately 80 percent of severe HPE have characteristic facial features. The least severe of the facial anomalies in holoprosencephaly is the median cleft lip (premaxillary agenesis). The most severe is cyclopia, an abnormality characterized by a single eye located in the area normally occupied by the root of the nose, and a missing nose or a proboscis (a tubular-shaped nose) located above the eye. The least common facial anomaly is ethmocephaly, in which a proboscis separates closely-set eyes. Cebocephaly, another facial anomaly, is characterized by a small, flattened nose with a single nostril situated below incomplete or underdeveloped closely-set eyes.

Not all individuals with HPE are affected to the same degree, even in families where more than one individual has this predisposition. This is why it is often helpful to discuss these issues with a professional in genetics who is trained to recognize features that might suggest that HPE is, or is not, likely to occur again in a family. The risk of reoccurrence is small in most families. There are a number of causes of HPE, including genetic alterations and environmental effects. The cause of HPE in any individual family is often unknown.

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Is there a test for holoprosencephaly?

The best diagnostic procedure is a brain scan (CT or MRI). Molecular testing for several HPE genes are available.

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Is there a treatment for holoprosencephaly?

Each child has a unique degree of malformations. Treatment must be individualized, although common problems occur. In general, treatment is largely symptomatic and supportive. Involvement in support groups and HPE Conferences are helpful (See: Additional Resources).

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What is the prognosis?

The prognosis for individuals with the disorder depends on the severity of the brain and facial malformations and associated clinical complications. The older literature suggested that the prognosis was uniformly poor. Recent studies show a broader range of outcomes than previously assumed.

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NHGRI Clinical Research on Holoprosencephaly

Clinical and Genetic Studies on Holoprosencephaly [clinicaltrials.gov]

The purpose of the present study is to increase our understanding of the genetic and clinical manifestations of HPE through detailed physical, psychological, developmental, neurologic endocrinologic, and radiologic studies. We also plan to examine the spectrum of clinical characteristics of HPE to facilitate early diagnosis and clinical management, including genetic counseling. Finally, we plan to assess the psychosocial impact of HPE on the family as a unit. To accomplish this, we plan to enroll approximately 60-80 affecteds and family members each year, with an enrollment ceiling of 250. Most patients and their families will be seen at the NIH Clinical Center. A subset may be examined outside the NIH, and a further subset, for the psychosocial studies, may be interviewed by phone.

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Additional Resources for Holoprosencephaly

About Holoprosencephaly
About Genetics

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Last Updated: January 3, 2012