What Is Holoprosencephaly?

Holoprosencephaly (HPE) is a birth defect of the brain that occurs shortly after conception. During embryo development, its incidence is approximately one in 250. In full-term babies, it occurs in roughly one in 10,000 to 20,000 infants. HPE occurs when the prosencephalon, or the embryonic forebrain, doesn’t divide into the two cerebral hemispheres.

In addition to the effects on the brain, it can also cause a small head size, eyes that are close together, and sometimes cleft palate or lip. When the defect is severe, it will cause death; when it is less severe, brain development can be normal or close to normal, with some facial deformities. Sometimes HPE is associated with other genetic syndromes as well.

Symptoms

Aside from the imaging findings of the brain, symptoms of HPE can vary widely depending on the type of HPE and the severity of the defect. Facial features of HPE can include cyclopia (a single, centered eye), anophthalmia (absent eyes), cleft lip or palate, a flattened nose, and closely-spaced eyes.

Other signs of HPE can include seizures, neural tube defects, short stature, difficulties with feeding, hydrocephalus, and unstable vital signs like temperature or heart rate.

Causes

Sometimes HPE is inherited, but not always. When there are hereditary causes of HPE, it could be due to a chromosome abnormality—this is the case for about one-third of those with HPE. This is caused by a single gene mutation that causes syndromic disorders, or a mutation of a gene that causes non-syndromic HPE.

Diabetes in the mother during pregnancy may increase the risk of fetal HPE, but this is fairly uncommon.

HPE affects males and females equally and has been diagnosed in a variety of ethnic groups.

Diagnosis

In addition to looking at medical history and doing a physical examination, a brain scan should be done on the infant—this can be either an MRI or CT scan. There is also molecular testing for a few HPE genes. Sometimes HPE can be diagnosed during pregnancy with ultrasound, but more mild versions of HPE may not be detected.

Talk with your doctor and a genetic counselor about whether molecular testing is right for you and how it might be helpful, especially if you plan to have subsequent children. Even if you decide not to get molecular testing, genetic testing and counseling are recommended for patients and their families once a diagnosis of HPE is made.

Classifications of HPE

There are several different classifications of HPE.

• Alobar. In this type, the brain is not divided into two hemispheres at all and facial deformities are typically severe, including a single eye or tubular-shaped nose
• Semilobar. With this type of HPE, the brain has somewhat divided into two hemispheres.
• Lobar. In lobar HPE, there is a significant amount of division into two hemispheres; this is the least severe form of the disorder and brain function might be nearly normal.
• Middle interhemispheric variant. The brain is fused in the middle with this type of HPE.

Treatment

There is no one set of treatments for HPE since each child with the condition has a specific set of symptoms and malformations, as well as a specific degree of severity. Treatment is personalized to the child and is largely supportive and focused on relieving symptoms.

Caring for a child with HPE is a multi-disciplinary effort and involves pediatricians, neurologists, dentists, psychologists, developmental pediatricians (and more) in order to provide the child and mother with the support, care, and treatment necessary.

Prognosis

In the past, the prognosis for children born with HPE was thought to be almost uniformly poor. Things have changed, however, and a prognosis really depends on the type of HPE an individual has, as well as the severity of the condition. For alobar HPE, the most severe type, a fetus with this condition may be stillborn or die within six months of being born.

More than half of children born with semi-lobar or lobar HPE without major malformations of other organs live to at least one year of age. Life expectancy can also depend on the underlying cause of the HPE, as well as any other syndromes that might be present and other malformations or abnormalities.

A Word From Verywell

If you have a child with HPE, talk with a specialist about the expected degree of HPE and what this could mean for your child. Due to the different subtypes of the condition as well as the wide range of severity, the prognosis for one child can be very different than that of another.