What is holoprosencephaly (HPE)?
Holoprosencephaly (HPE), pronounced “hah-low-prah-sen-SEH-fuh-lee,” is a birth defect (congenital condition) that causes a developing baby’s brain to not properly separate into the right and left hemispheres (halves). HPE can also affect the development of an unborn baby’s head and face.
Your brain is normally divided into the left and right hemispheres, but they remain in contact and communication with one another by the corpus callosum (a nerve fiber bundle in your brain). Each hemisphere further divides into the frontal, parietal, occipital and temporal lobes.
This division is important for several reasons, including allowing your brain to process several pieces of information and to perform several actions at once. When your brain doesn’t divide properly in development, as in HPE, it causes several physical and neurological issues.
Holoprosencephaly happens very early in fetal development in the womb. There are several different types of holoprosencephaly with a wide range of severity and symptoms. The condition affects each child differently.
What are the symptoms of holoprosencephaly (HPE)?
As there are several types of holoprosencephaly (HPE), the severity and symptoms for it vary widely.
In general, HPE is associated with the following symptoms:
Signs and symptoms of alobar holoprosencephaly include:
- A single eye (cyclopia), very closely spaced eyes (ethmocephaly) or missing eyes (anophthalmia).
- Very small eyeballs (microphthalmia) with a tubular-shaped nose (proboscis).
- Closely spaced eyes (orbital hypotelorism) with a flattened nose or cleft lip that occurs in the middle of their lip (median cleft lip) or on both sides (bilateral cleft lip).
Signs and symptoms of semilobar holoprosencephaly include:
- Closely spaced eyes (orbital hypotelorism), very small eyeballs (microphthalmia) or one or no eyes (anophthalmia).
- Flattened bridge and tip of their nose.
- One nostril.
- Median cleft lip or bilateral cleft lip.
- Cleft palate.
Signs and symptoms of lobar holoprosencephaly include:
- Bilateral cleft lip.
- Closely spaced eyes.
- Depressed nose.
Holoprosencephaly may be part of several different genetic syndromes. Each of these syndromes has its own characteristics and symptoms.
What causes holoprosencephaly (HPE)?
Normally, your fetus’s brain divides into two hemispheres (halves) during early development. Holoprosencephaly (HPE) happens when their brain doesn’t divide properly into the right and left hemispheres, specifically in their forebrain, or prosencephalon.
The forebrain is a region of your fetus’s brain that develops into parts of their adult brain, including their cerebral cortex. Instead of the normal complete separation of the left and right hemispheres of their forebrain, there’s an abnormal continuity between the two sides.
Specifically, causes of holoprosencephaly can include:
- Mutations (changes) in any of at least 14 different genes.
- Chromosome abnormalities.
- Certain genetic syndromes.
In many cases, healthcare providers can’t determine the exact cause.
Genetic mutations that cause holoprosencephaly
A genetic mutation is a change in a sequence of your DNA. Your DNA sequence gives your cells the information they need to perform their functions. If part of your DNA sequence isn’t complete or is damaged, you might experience symptoms of a genetic condition.
A baby can inherit a genetic mutation from either or both of their biological parents, depending on how the mutation is passed down, but some mutations occur randomly with no previous history of the mutation in your family.
Scientists have connected mutations in these specific genes to HPE:
- SHH.
- SIX3.
- TGIF1.
- ZIC2.
- PTCH1.
- FOXH1.
- NODAL.
- CDON.
- FGF8.
- GLI2.
These mutations (changes) cause the genes and their proteins to function incorrectly, and this affects the development of your unborn baby’s brain, resulting in holoprosencephaly.
Chromosome abnormalities that cause holoprosencephaly
All humans have 46 chromosomes that divide into 23 pairs. Chromosomes carry your DNA in cells, which tells your body how to form and function as its instruction manual. You receive one set of chromosomes from each of your parents.
About one-third of babies born with holoprosencephaly have an abnormality of their chromosomes. The most common chromosomal abnormality associated with HPE is when there are three copies of chromosome 13 (trisomy 13). Trisomy 18 and triploidy (having 69 chromosomes rather than the normal 46 chromosomes per cell) also cause HPE.
Genetic syndromes that involve holoprosencephaly
Holoprosencephaly can occur as a part of certain genetic syndromes in which there are other medical issues besides HPE.
Genetic syndromes that involve HPE include:
- Hartsfield syndrome.
- Kallman syndrome two.
- Steinfeld syndrome.
- Smith-Lemli-Opitz syndrome.
- Stromme syndrome.
Healthcare providers can often identify holoprosencephaly (HPE), especially more severe cases, before your baby is born through a prenatal ultrasound. They can also diagnose the condition pre-birth with fetal magnetic resonance imaging (MRI).
Although healthcare providers can identify HPE with prenatal imaging, they most frequently diagnose HPE after your baby is born when facial abnormalities or neurologic issues are present. They then perform head imaging tests to confirm the diagnosis.
Infants with very mild forms of holoprosencephaly may not be diagnosed until they’re about one year old. In this case, developmental delays often signal a possible neurological issue, which then prompts healthcare providers to order brain imaging tests.
What tests will be done to diagnose holoprosencephaly (HPE)?
Healthcare providers use the following imaging tests to help diagnose holoprosencephaly once your baby is born:
- Head ultrasound: Ultrasound (also called sonography or ultrasonography) is a noninvasive diagnostic imaging test. It uses high-frequency sound waves to create real-time pictures or video of internal organs or other tissues, such as blood vessels.
- Magnetic resonance imaging (MRI) brain scan: An MRI brain scan is a painless test that produces very clear images of the structures and tissues in your child’s brain. MRI uses a large magnet, radio waves and a computer to produce these detailed images. It doesn’t use X-rays (radiation).
- Head computed tomography (CT) scan: A CT scan is a type of test that combines X-rays with a computer to produce many three-dimensional (3D) images of the body part being scanned — in this case, your child’s head and brain.
Healthcare providers use DNA studies, such as chromosomal analysis and cytogenetic and molecular testing, to determine the exact cause of HPE, if possible.
If genetic testing reveals any kind of chromosomal or genetic issue that’s associated with holoprosencephaly, your healthcare provider will recommend genetic counseling if you’re considering having another biological child.
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